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Clinical Trial Results:
Assessment of long-term antibody persistence and immunological memory in children previously vaccinated with four pneumococcal conjugate vaccine doses and assessment of pneumococcal catch-up vaccination with GSK1024850A at 5 years of age.

Summary
EudraCT number	2007-005392-34
Trial protocol	PL
Global end of trial date	21 Nov 2011

Results information
Results version number	v5(current)
This version publication date	18 Feb 2021
First version publication date	30 Jul 2015
Other versions	v1 (removed from public view) , v2 , v3 , v4
Version creation reason	Correction of full data set Results have been amended to account for consistency with other registries.

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

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Trial information

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Sponsor protocol code

111345

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

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

Public contact

GSK Response Center, GSKClinicalSupportHD, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 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

14 Oct 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Nov 2011

Global end of trial reached?

Yes

Global end of trial date

21 Nov 2011

Was the trial ended prematurely?

Main objective of the trial

To assess antibody persistence in children previously vaccinated with four doses of pneumococcal conjugate vaccine in primary vaccination study 10PN-PD-DIT-001 and booster vaccination study 10PN-PD-DIT-007.

Protection of trial subjects

The vaccinees was observed closely for at least 30 minutes following the administration of vaccine, with appropriate medical treatment readily available in case of a rare anaphylactic reaction.

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Mar 2008

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 524

Worldwide total number of subjects

524

EEA total number of subjects

524

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)

Children (2-11 years)

524

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Primed groups included Synflorix vaccinated subjects in study 10PN-PD-DIT-007. The Unprimed Group, added only in Year 4,included subjects unprimed with any pneumococcal vaccine age-matched with primed groups. The study included 3 sub-studies (111345, 111346, 111347) corresponding to Year 1, 2 and 4 time points post Dose 1 in Study 10PN-PD-DIT-001.

Screening details

At screening, subjects with previous participation in 10PN-PD-DIT-007 study were invited to join this study. Informed consent was obtained and signed from subjects’ parents/guardians, check for inclusion/exclusion criteria and contraindications/precautions was performed, and medical history of subjects was collected.

Period 1 title

Follow-up Period: Year 1

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Synflorix + Infanrix + Havrix and/or Varilrix Group

Arm description

This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).

Arm type

Experimental

Investigational medicinal product name

10 valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses in primary vaccination study 10PN-PD-DT-001 (1105553); 1 dose in booster vaccination study 10PN-PD-DIT-007 (107046);

Investigational medicinal product name

Havrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were proposed post blood sampling procedure to subjects from all three primed groups.

Investigational medicinal product name

Varilrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

One dose was proposed post blood sampling procedure to subjects from all three primed groups.

Prevenar + Infanrix + Havrix and/or Varilrix Group

Arm description

This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses in primary vaccination study 10PN-PD-DT-001 (1105553); 1 dose in booster vaccination study 10PN-PD-DIT-007 (107046)

Investigational medicinal product name

Havrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were proposed post blood sampling procedure to subjects from all three primed groups.

Investigational medicinal product name

Varilrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

One dose was proposed post blood sampling procedure to subjects from all three primed groups.

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Arm description

This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).

Arm type

Control

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses in primary vaccination study 10PN-PD-DT-001 (1105553)

Investigational medicinal product name

10 valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose in booster study 10PN-PD-DIT-007 (107046)

Investigational medicinal product name

Havrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were proposed post blood sampling procedure to subjects from all three primed groups.

Investigational medicinal product name

Varilrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

One dose was proposed post blood sampling procedure to subjects from all three primed groups.

Number of subjects in period 1	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Started	391	31	102
Completed	391	31	102

Period 2 title

Follow-up Period: Year 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Synflorix + Infanrix + Havrix and/or Varilrix Group

Arm description

Arm type

Experimental

Investigational medicinal product name

10 valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses in primary vaccination study 10PN-PD-DT-001 (1105553); 1 dose in booster vaccination study 10PN-PD-DIT-007 (107046);

Investigational medicinal product name

Havrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were proposed post blood sampling procedure to subjects from all three primed groups.

Investigational medicinal product name

Varilrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

One dose was proposed post blood sampling procedure to subjects from all three primed groups.

Prevenar + Infanrix + Havrix and/or Varilrix Group

Arm description

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses in primary vaccination study 10PN-PD-DT-001 (1105553); 1 dose in booster vaccination study 10PN-PD-DIT-007 (107046)

Investigational medicinal product name

Havrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were proposed post blood sampling procedure to subjects from all three primed groups.

Investigational medicinal product name

Varilrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

One dose was proposed post blood sampling procedure to subjects from all three primed groups.

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Arm description

Arm type

Control

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses in primary vaccination study 10PN-PD-DT-001 (1105553)

Investigational medicinal product name

10 valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, Synflorix

Pharmaceutical forms

Powder for suspension for injection, Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose in booster study 10PN-PD-DIT-007 (107046)

Investigational medicinal product name

Havrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were proposed post blood sampling procedure to subjects from all three primed groups.

Investigational medicinal product name

Varilrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

One dose was proposed post blood sampling procedure to subjects from all three primed groups.

Number of subjects in period 2 ^[1]	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Started	370	31	96
Completed	370	31	96

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: Out of the 524 subjects who participated to the year 1 persistence analysis in study 111345, 497 returned participating to the year 2 persistence analysis in study 111346 and 27 were lost to follow-up (FU).

Period 3 title

Follow-up Period: Year 4 Persistence

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Synflorix + Infanrix + Havrix and/or Varilrix Group

Arm description

Arm type

Experimental

Investigational medicinal product name

10Pn-PD-DiT

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Route of administration not applicable

Dosage and administration details

4 doses received in primary vaccination study 10PN-PD-DT-001 (1105553) and in booster vaccination study 10PN-PD-DIT-007 (107046); 1 dose during this study at follow-up visit (Visit 3)

Prevenar + Infanrix + Havrix and/or Varilrix Group

Arm description

Arm type

Control

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

4 doses received in primary vaccination study 10PN-PD-DT-001 (1105553) and in booster vaccination study 10PN-PD-DIT-007 (107046)

Investigational medicinal product name

10Pn-PD-DiT

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose at follow-up visit (Visit 3)

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Arm description

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses received in primary vaccination study 10PN-PD-DT-001 (1105553)

Investigational medicinal product name

10Pn-PD-DiT

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose in booster study 10PN-PD-DIT-007 (107046); 1 dose during this study at follow-up visit (Visit 3)

Number of subjects in period 3 ^[2]	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Started	316	25	85
Completed	316	25	85

Notes
[2] - 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: Out of the 497 subjects who participated to the year 2 persistence analysis in study 111346, 426 returned participating to the year 4 persistence analysis in study 111347 and 71 were lost to follow-up (FU).

Period 4 title

Follow-up Period: Year 4 Immunogenicity

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Synflorix + Infanrix + Havrix and/or Varilrix Group

Arm description

Arm type

Experimental

Investigational medicinal product name

10Pn-PD-DiT

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Route of administration not applicable

Dosage and administration details

4 doses received in primary vaccination study 10PN-PD-DT-001 (1105553) and in booster vaccination study 10PN-PD-DIT-007 (107046); 1 dose during this study at follow-up visit (Visit 3)

Prevenar + Infanrix + Havrix and/or Varilrix Group

Arm description

Arm type

Control

Investigational medicinal product name

10Pn-PD-DiT

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose at follow-up visit (Visit 3)

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

4 doses received in primary vaccination study 10PN-PD-DT-001 (1105553) and in booster vaccination study 10PN-PD-DIT-007 (107046)

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Arm description

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses received in primary vaccination study 10PN-PD-DT-001 (1105553)

Investigational medicinal product name

10Pn-PD-DiT

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose in booster study 10PN-PD-DIT-007 (107046); 1 dose during this study at follow-up visit (Visit 3)

Number of subjects in period 4 ^[3]	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Started	264	20	65
Completed	263	19	64
Not completed	1	1	1
Parents’ Decision	-	-	1
Lost to follow-up	1	1	-

Notes
[3] - 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: Out of the 426 subjects who participated to the year 4 persistence analysis in study 111347, 349 participated to the Immunological Memory phase in this study 111347 and 77 were lost to follow-up/did not participate to this 2nd phase. Kindly note that to these 349 subjects, 100 additional subjects were added, who constituted an Unprimed Group. No withdrawal was reported for this group, which included 53 females and 47 males and in which mean age was 65.4 months (SD: 1.31 months).

Baseline characteristics

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Reporting group title

Synflorix + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Reporting group description

Reporting group values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Total
Number of subjects	391	31	102	524
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)	0	0	0	0
Children (2-11 years)	391	31	102	524
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
Data was presented for Follow-up Period: Year 1
Units: Months
arithmetic mean (standard deviation)	29.1 ± 0.88	29.0 ± 0.75	29.1 ± 0.81	-
Sex: Female, Male
Data was presented for Follow-up Period Year 1
Units: Participants
Female	203	14	52	269
Male	188	17	50	255
Race/Ethnicity, Customized
Data was presented for Follow-up Period: Year 1
Units: Subjects
White - caucasia/ european heritage	386	31	102	519
White arabic/ north african heritage	4	0	0	4
Other, not specified	1	0	0	1
Asian - Central/South Asian heritage	0	0	0	0

Subject analysis set title

Unprimed Group

Subject analysis set type

Per protocol

Subject analysis set description

This group consisted of subjects between, and including, 64-68 months of age at the time of additional vaccination (primed subjects) or dose 1 (unprimed subjects), and for whom the investigator believed that their parents/guardians could and would comply with the requirements of the protocol. Subjects were not previously vaccinated with any pneumococcal vaccine and received 2 doses of Synflorix vaccine at 64-68 and 66-70 months of age (at Day 0 and Month 2). The Unprimed Group was added only in Year 4 of the study.

Subject analysis sets values	Unprimed Group
Number of subjects	100
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	100
Adolescents (12-17 years)	0
Adults (18-64 years)	0
From 65-84 years	0
85 years and over	0
Age Continuous
Data was presented for Follow-up Period: Year 1
Units: Months
arithmetic mean (standard deviation)	65.4 ± 1.31
Sex: Female, Male
Data was presented for Follow-up Period Year 1
Units: Participants
Female	53
Male	47
Race/Ethnicity, Customized
Data was presented for Follow-up Period: Year 1
Units: Subjects
White - caucasia/ european heritage	98
White arabic/ north african heritage	1
Other, not specified	1
Asian - Central/South Asian heritage	1

End points

Top of page

Reporting group title

Synflorix + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Reporting group description

Reporting group title

Synflorix + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Reporting group description

Reporting group title

Synflorix + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Reporting group description

Reporting group title

Synflorix + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Reporting group description

Subject analysis set title

Unprimed Group

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations greater than or equal to (≥) the cut-off [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

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End point title

Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations greater than or equal to (≥) the cut-off [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)] ^[1]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using 0.05 microgram per milliliter (µg/mL) as seropositivity cut off.

End point type

Primary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

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

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	389	31	102
Units: Participants
Anti-1 antibodies, Y1 (N= 387, 29, 102)	372	7	99
Anti-4 antibodies, Y1 (N= 387, 31, 102)	384	31	102
Anti-5 antibodies, Y1 (N= 387, 30, 101)	386	19	101
Anti-6B antibodies, Y1 (N= 389, 31, 102)	384	31	100
Anti-7F antibodies, Y1 (N= 387, 31, 102)	387	17	102
Anti-9V antibodies, Y1 (N= 388, 31, 102)	388	17	102
Anti-14 antibodies, Y1 (N= 388, 31, 102)	387	31	102
Anti-18C antibodies, Y1 (N= 384, 31, 102)	384	31	102
Anti-19F antibodies, Y1 (N= 387, 31, 102)	387	31	102
Anti-23F antibodies, Y1 (N= 388, 31, 102)	386	31	102

No statistical analyses for this end point

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Top of page

End point title

Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 2 (111346 sub-study)] ^[2]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme -linked immunosorbent assay (ELISA), using 0.05 μg/mL as seropositivity cut off.

End point type

Primary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)

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

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	368	30	96
Units: Participants
Anti-1 antibodies, Y2 (N= 367, 29, 96)	354	18	90
Anti-4 antibodies, Y2 (N= 368, 30, 96)	356	30	96
Anti-5 antibodies, Y2 (N= 368, 29, 95)	362	21	95
Anti-6B antibodies, Y2 (N= 368, 30, 96)	355	30	95
Anti-7F antibodies, Y2 (N= 368, 30, 96)	367	19	95
Anti-9V antibodies, Y2 (N= 368, 30, 96)	362	30	96
Anti-14 antibodies, Y2 (N= 368, 30, 96)	367	30	96
Anti-18C antibodies, Y2 (N= 368, 30, 96)	365	30	96
Anti-19F antibodies, Y2 (N= 368, 30, 95)	368	30	95
Anti-23F antibodies, Y2 (N= 368, 30, 96)	357	30	95

No statistical analyses for this end point

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)] ^[3]

End point description

End point type

Primary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)

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

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	264	19	75
Units: Participants
Anti-1 antibodies, Y4 (N= 263, 19, 75)	238	14	75
Anti-4 antibodies, Y4 (N= 263, 18, 74)	238	18	74
Anti-5 antibodies, Y4 (N= 263, 19, 74)	257	19	73
Anti-6B antibodies, Y4 (N= 263, 19, 75)	258	19	74
Anti-7F antibodies, Y4 (N= 263, 19,75)	260	13	73
Anti-9V antibodies, Y4 (N= 263, 19, 75)	255	19	75
Anti-14 antibodies, Y4 (N= 263, 19, 75)	2633	19	75
Anti-18C antibodies, Y4 (N= 263, 19, 74)	256	19	73
Anti-19F antibodies, Y4 (N= 263, 19, 75)	260	19	75
Anti-23F antibodies, Y4 (N= 262, 19, 75)	254	19	74

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

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End point title

Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

End point description

Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL).The seropositivity cut-off for the assay was ≥ 0.05 µg/mL.

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	389	31	102
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 antibodies, Y1 (N= 387, 29, 102)	0.29 (0.27 to 0.32)	0.04 (0.03 to 0.06)	0.26 (0.21 to 0.31)
Anti-4 antibodies, Y1 (N= 387, 31, 102)	0.5 (0.45 to 0.55)	0.59 (0.46 to 0.75)	1.01 (0.84 to 1.21)
Anti-5 antibodies, Y1 (N= 387, 30, 101)	0.59 (0.54 to 0.65)	0.07 (0.05 to 0.11)	0.42 (0.35 to 0.52)
Anti-6B antibodies, Y1 (N= 389, 31, 102)	0.52 (0.45 to 0.6)	0.98 (0.63 to 1.53)	0.54 (0.42 to 0.69)
Anti-7F antibodies, Y1 (N= 387, 31, 102)	0.71 (0.66 to 0.77)	0.08 (0.05 to 0.13)	0.83 (0.7 to 0.99)
Anti-9V antibodies, Y1 (N= 388, 31, 102)	0.79 (0.71 to 0.89)	0.93 (0.7 to 1.22)	0.58 (0.49 to 0.68)
Anti-14 antibodies, Y1 (N= 388, 31, 102)	1.27 (1.12 to 1.44)	1.79 (1.29 to 2.48)	1.47 (1.17 to 1.85)
Anti-18C antibodies, Y1 (N= 384, 31, 102)	0.88 (0.81 to 0.96)	0.91 (0.71 to 1.16)	0.82 (0.69 to 0.98)
Anti-19F antibodies, Y1 (N= 387, 31, 102)	1.43 (1.27 to 1.6)	0.83 (0.47 to 1.45)	1.51 (1.19 to 1.92)
Anti-23F antibodies, Y1 (N= 388, 30, 102)	0.61 (0.54 to 0.69)	1.18 (0.84 to 1.68)	0.7 (0.56 to 0.88)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

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End point title

Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

End point description

Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 µg/mL.

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	368	30	96
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 antibodies, Y2 (N= 367, 29, 96)	0.19 (0.17 to 0.21)	0.07 (0.05 to 0.10)	0.17 (0.14 to 0.20)
Anti-4 antibodies, Y2 (N= 368, 30, 96)	0.27 (0.24 to 0.3)	0.3 (0.24 to 0.38)	0.52 (0.43 to 0.64)
Anti-5 antibodies, Y2 (N= 368, 29, 95)	0.41 (0.37 to 0.45)	0.09 (0.06 to 0.13)	0.33 (0.27 to 0.41)
Anti-6B antibodies, Y2 (N= 368, 30, 96)	0.70 (0.58 to 0.83)	0.99 (0.57 to 1.71)	0.9 (0.63 to 1.29)
Anti-7F antibodies, Y2 (N= 368, 30, 96)	0.53 (0.48 to 0.58)	0.1 (0.06 to 0.16)	0.59 (0.49 to 0.71)
Anti-9V antibodies, Y2 (N= 368, 30, 96)	0.64 (0.54 to 0.75)	0.61 (0.37 to 1)	0.5 (0.37 to 0.68)
Anti-14 antibodies, Y2 (N= 368, 30, 96)	1.73 (1.48 to 2.02)	1.94 (1.12 to 3.36)	1.7 (1.25 to 2.31)
Anti-18C antibodies, Y2 (N= 368, 30, 96)	0.54 (0.48 to 0.62)	0.59 (0.39 to 0.88)	0.48 (0.38 to 0.59)
Anti-19F antibodies, Y2 (N= 368, 30, 95)	2.16 (1.77 to 2.65)	0.99 (0.51 to 1.91)	2.41 (1.67 to 3.46)
Anti-23F antibodies, Y2 (N= 368, 30, 96)	0.68 (0.56 to 0.82)	1.24 (0.83 to 1.85)	0.64 (0.48 to 0.86)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Antibody concentrations against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

Pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PDDIT- 007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	264	19	75
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-1 antibodies, Y4 (N= 263, 19, 75)	0.2 (0.17 to 0.24)	0.17 (0.07 to 0.43)	0.23 (0.17 to 0.32)
Anti-4 antibodies, Y4 (N= 263, 19, 74)	0.19 (0.16 to 0.22)	0.23 (0.12 to 0.41)	0.31 (0.25 to 0.38)
Anti-5 antibodies, Y4 (N= 263, 19, 74)	0.36 (0.31 to 0.4)	0.19 (0.1 to 0.35)	0.35 (0.28 to 0.43)
Anti-6B antibodies, Y4 (N= 263, 19, 75)	1.3 (1.1 to 1.55)	1.19 (0.68 to 2.07)	0.97 (0.74 to 1.27)
Anti-7F antibodies, Y4 (N= 263, 19, 75)	0.44 (0.38 to 0.52)	0.16 (0.08 to 0.36)	0.49 (0.37 to 0.65)
Anti-9V antibodies, Y4 (N= 263, 19, 75)	1.17 (0.92 to 1.47)	1.19 (0.43 to 3.27)	0.67 (0.46 to 0.99)
Anti-14 antibodies, Y4 (N= 263, 19, 75)	3.66 (3.01 to 4.45)	2.57 (1.22 to 5.42)	2.94 (2.11 to 4.12)
Anti-18C antibodies, Y4 (N= 263, 19, 74)	0.7 (0.58 to 0.84)	0.87 (0.4 to 1.88)	0.63 (0.45 to 0.89)
Anti-19F antibodies, Y4 (N= 263, 19, 75)	4.17 (3.4 to 5.1)	4.74 (2.24 to 10)	4.05 (3.03 to 5.41)
Anti-23F antibodies, Y4 (N= 262, 19, 75)	1.57 (1.26 to 1.96)	1.64 (1.15 to 2.34)	1.12 (0.79 to 1.58)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Antibody concentrations against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

Anti-pneumococcal serotypes assessed were serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F . Antibody concentrations against pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.

End point type

Secondary

End point timeframe

For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	210	14	55	98
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-1 antibodies, PRE (N=0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.1 (0.08 to 0.13)
Anti-1 antibodies, D7 (N= 208, 14, 54, 98)	5.36 (4.54 to 6.33)	3.04 (1.22 to 7.56)	5 (3.72 to 6.71)	1.35 (1.08 to 1.69)
Anti-1 antibodies, M3 (N=0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	2.39 (2.06 to 2.78)
Anti-4 antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.04 (0.03 to 0.05)
Anti-4 antibodies, D7 (N=208, 14, 54, 98)	12.11 (10.08 to 14.54)	10.45 (6.49 to 16.81)	7.13 (5.18 to 9.82)	4.74 (3.77 to 5.95)
Anti-4 antibodies, M3 (N=0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	7.32 (6.7 to 8)
Anti-5 antibodies, PRE (N=0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.1 (0.08 to 0.12)
Anti-5 antibodies, D7 (N=208, 14, 54, 98)	6.23 (5.19 to 7.49)	3.24 (1.44 to 7.29)	8.15 (5.71 to 11.63)	1.2 (0.97 to 1.49)
Anti-5 antibodies, M3 (N=0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	3.1 (2.7 to 3.55)
Anti-6B antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.21 (0.15 to 0.29)
Anti-6B antibodies, D7 (N= 208, 14, 54, 97)	3.68 (3.16 to 4.28)	2.85 (1.89 to 4.3)	2.15 (1.62 to 2.85)	0.53 (0.4 to 0.71)
Anti-6B antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	1.25 (1.01 to 1.54)
Anti-7F antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.12 (0.09 to 0.16)
Anti-7F antibodies, D7 (N=208, 14, 54, 98)	7.16 (6.11 to 8.39)	3.26 (1.67 to 6.35)	7.57 (5.84 to 9.81)	1.67 (1.33 to 2.09)
Anti-7F antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	4.55 (3.93 to 5.26)
Anti-9V antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.19 (0.12 to 0.28)
Anti-9V antibodies, D7 (N=208, 14, 54, 98)	9.94 (8.59 to 11.51)	9 (5.49 to 14.77)	5.32 (4.08 to 6.94)	0.9 (0.66 to 1.23)
Anti-9V antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	2.2 (1.85 to 2.62)
Anti-14 antibodies, PRE (N= 0, 0, 0, 96)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.58 (0.38 to 0.87)
Anti-14 antibodies, D7 (N= 208, 14, 54, 98)	19.38 (16.74 to 22.43)	13.26 (6.91 to 25.43)	18.61 (14.23 to 24.34)	1.72 (1.2 to 2.46)
Anti-14 antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	7.81 (6.34 to 9.63)
Anti-18C antibodies, PRE (N= 0, 0, 0, 96)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.1 (0.07 to 0.15)
Anti-18C antibodies, D7 (N=208, 14, 54, 98)	15.51 (13.06 to 18.43)	19.71 (11.87 to 32.74)	13.34 (9.34 to 19.05)	2.26 (1.66 to 3.09)
Anti-18C antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	13.21 (11.44 to 15.25)
Anti-19F antibodies, PRE (N= 0, 0, 0, 96)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.6 (0.4 to 0.89)
Anti-19F antibodies, D7 (N=208, 14, 54, 98)	11.63 (10 to 13.51)	16.44 (10.68 to 25.29)	8.09 (6.29 to 10.42)	5.12 (3.97 to 6.62)
Anti-19F antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	15.47 (13.08 to 18.29)
Anti-23F antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.1 (0.07 to 0.14)
Anti-23F antibodies, D7 (N= 208, 14, 54, 98)	6.5 (5.61 to 7.53)	9.34 (5.62 to 15.54)	4.7 (3.43 to 6.45)	0.42 (0.3 to 0.59)
Anti-23F antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	1.63 (1.32 to 2.01)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

End point description

Pneumococcal serotypes assessed were OPA-1, OPA-4, OPA-5, OPA-6B, OPA-7F, OPA-9V, OPA-14, OPA-18C, OPA-19F and OPA-23F. The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	359	27	94
Units: Titer
geometric mean (confidence interval 95%)
Anti-1 OPA Titers, Y1 (N=354, 27, 92)	16.2 (13.8 to 19)	4.8 (3.6 to 6.4)	7.3 (5.9 to 9)
Anti-4 OPA Titers, Y1 (N= 340, 26, 86)	59.8 (45.7 to 78.3)	192.9 (82.4 to 452)	88.9 (54.6 to 144.6)
Anti-5 OPA Titers, Y1 (N=335, 27, 89)	24.2 (20.8 to 28.2)	5.1 (3.6 to 7.4)	11.2 (8.7 to 14.3)
Anti-6B OPA Titers, Y1 (N=354, 25, 88)	35.5 (26.5 to 47.5)	476.9 (175.3 to 1298)	44.7 (24 to 83.3)
Anti-7F OPA Titers, Y1 (N= 346, 25, 89)	1855.7 (1644.4 to 2094.1)	350.4 (121.8 to 1008)	1617.2 (1152.9 to 2268.3)
Anti-9V OPA Titers, Y1 (N=352, 26, 94)	791.5 (701.8 to 892.8)	1240.7 (829.4 to 1855.9)	370.5 (281.8 to 487.2)
Anti-14 OPA Titers, Y1 (N= 343, 25, 91)	551.9 (486.5 to 626.2)	607.3 (385.3 to 957.1)	456.6 (361.1 to 577.3)
Anti-18C OPA Titers, Y1 (N= 319, 24, 84)	23.5 (18.6 to 29.8)	15.5 (6.1 to 39.2)	10.4 (7.1 to 15.4)
Anti-19F OPA Titers, Y1 (N= 359, 27, 94)	53.4 (44.7 to 63.9)	35.4 (15.9 to 78.6)	58 (41.6 to 80.7)
Anti-23F OPA Titers, Y1 (N= 336, 27, 93)	784.9 (625.4 to 985)	3013.1 (1349.5 to 6727.2)	552.3 (362.1 to 842.5)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

End point description

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	354	27	92
Units: Titer
geometric mean (confidence interval 95%)
Anti-1 OPA Titers, Y2 (N= 354, 27, 92)	8.4 (7.3 to 9.7)	4 (4 to 4)	6.3 (4.9 to 8)
Anti-4 OPA Titers, Y2 (N= 335, 27, 84)	29 (22.1 to 38)	33.5 (11.9 to 94.6)	39.3 (23.7 to 65.2)
Anti-5 OPA Titers, Y2 (N= 351, 27, 91)	11.4 (10 to 13)	4.3 (3.9 to 4.7)	7.4 (6 to 9.1)
Anti-6B OPA Titers, Y2 (N= 342, 27, 88)	167.2 (124.1 to 225.2)	526.1 (210.5 to 1314.4)	213.7 (117.8 to 387.6)
Anti-7F OPA Titers, Y2 (N= 350, 27, 91)	1488.7 (1358.3 to 1631.6)	1068.3 (619.5 to 1842.4)	1387.8 (1096.2 to 1756.9)
Anti-9V OPA Titers, Y2 (N= 349, 27, 92)	648.5 (570 to 737.7)	730.4 (457.7 to 1165.7)	391 (279.2 to 547.5)
Anti-14 OPA Titers, Y2 (N= 341, 25, 90)	660.2 (567.2 to 768.4)	651 (348.6 to 1215.5)	391 (279.2 to 547.5)
Anti-18C OPA Titers, Y2 (N= 325, 27, 83)	34.9 (26.6 to 45.7)	34.8 (11.7 to 103.2)	17.7 (10.7 to 29.2)
Anti-19F OPA Titers, Y2 (N= 349, 27, 92)	78.1 (60.9 to 100.2)	49.2 (21.2 to 113.9)	105.4 (65.8 to 168.7)
Anti-23F OPA Titers, Y2 (N= 342, 26, 91)	632 (483 to 827)	1923 (952.2 to 3883.7)	435 (250.5 to 755.5)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

Pneumococcal serotypes assessed were pneumococcal serotypes OPA-1, OPA-4, OPA-5, OPA-6B, OPA-7F, OPA-9V, OPA-14, OPA-18C, OPA-19F and OPA-23F. The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administrated in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	253	16	72
Units: Titer
geometric mean (confidence interval 95%)
Anti-1 OPA Titers, Y4 (N= 250, 16, 72)	8.8 (7.1 to 10.9)	4.6 (3.4 to 6.4)	8.9 (5.9 to 13.2)
Anti-4 OPA Titers, Y4 (N= 232, 16, 63)	37.9 (27.2 to 52.8)	62.2 (13.6 to 284.7)	50.7 (26.5 to 97)
Anti-5 OPA Titers, Y4 (N= 243, 15, 68)	7.7 (6.8 to 8.9)	5.3 (3.5 to 8.1)	5.5 (4.5 to 6.6)
Anti-6B OPA Titers, Y4 (N= 250, 16, 68)	875.7 (658.7 to 1164.3)	978.3 (395.3 to 2421.3)	716.4 (417.4 to 1229.7)
Anti-7F OPA Titers, Y4 (N= 249, 15, 71)	1693.1 (1489.3 to 1924.8)	965.8 (666.8 to 1398.9)	1602.2 (1286.9 to 1994.5)
Anti-9V OPA Titers, Y4 (N= 250, 15, 70)	747.4 (624.9 to 894.1)	563.8 (220.2 to 1444)	558.6 (403 to 774.2)
Anti-14 OPA Titers, Y4 (N= 250, 15, 71)	1139.8 (961.9 to 1350.5)	687.9 (267.8 to 1767.4)	849.4 (645.4 to 1117.8)
Anti-18C OPA Titers, Y4 (N= 226, 16, 63)	46.4 (33.3 to 64.5)	35.3 (8.8 to 142.5)	26.6 (14.3 to 49.3)
Anti-19F OPA Titers, Y4 (N= 247, 16, 69)	151.7 (115.9 to 198.4)	178.8 (64.6 to 495.1)	129.3 (83.1 to 201.4)
Anti-23F OPA Titers, Y4 (N= 239, 15, 65)	1518.4 (1107.9 to 2080.9)	3366.1 (1599.2 to 7085.1)	1146.2 (596.8 to 2201.3)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	204	13	54	96
Units: Titers
geometric mean (confidence interval 95%)
Anti-1 OPA Titers, PRE (N= 0, 0, 0, 94)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	5 (4.2 to 5.9)
Anti-1 OPA Titers, D7 (N= 197, 13, 50, 92)	2920.8 (2353.5 to 3624.7)	1331 (586.7 to 3019.5)	1816.1 (1090 to 3025.8)	605 (462.7 to 791.2)
Anti-1 OPA Titers, M3 (N= 0, 0, 0, 95)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	128.3 (97.3 to 169.1)
Anti-4 OPA Titers, PRE (N= 0, 0, 0, 81)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	11.5 (7.2 to 18.3)
Anti-4 OPA Titers, D7 (N=196, 13, 51, 93)	23633.7 (19118.5 to 29215.3)	10650.3 (3969.2 to 28577.6)	8592.8 (5609.3 to 13163.1)	18262.1 (15571.6 to 21417.4)
Anti-4 OPA Titers, M3 (N= 0, 0, 0, 94)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	4451.3 (3962.4 to 5000.6)
Anti-5 OPA Titers, PRE (N= 0, 0, 0, 91)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	4.9 (4.3 to 5.7)
Anti-5 OPA Titers, D7 (N= 193, 13, 48, 91)	822.3 (662.7 to 1020.3)	375.6 (217.4 to 648.9)	683.6 (428.6 to 1090.2)	295.6 (219.4 to 398.3)
Anti-5 OPA Titers, M3 (N= 0, 0, 0, 92)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	93.2 (73.7 to 117.8)
Anti-6B OPA Titers, PRE (N= 0, 0, 0, 79)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	70.7 (33.5 to 149.2)
Anti-6B OPA Titers, D7 (N= 198, 13, 50, 93)	3513.1 (2858.1 to 4318.1)	3566.6 (2446.1 to 5200.3)	1590.5 (942.8 to 2683.3)	1971.4 (1238 to 3139.2)
Anti-6B OPA Titers, M3 (N= 0, 0, 0, 95)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	2536.9 (2014.1 to 3195.5)
Anti-7F OPA Titers, PRE (N= 0, 0, 0, 74)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	1368.2 (849.6 to 2185.8)
Anti-7F OPA Titers, D7 (N= 199, 13, 50, 93)	25196.4 (21149.5 to 30017.6)	17828.8 (10270.4 to 30949.7)	13098.6 (9715.5 to 17659.8)	19243.4 (15701.4 to 23584.5)
Anti-7F OPA Titers, M3 (N= 0, 0, 0, 93)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	9692 (8299.3 to 11318.4)
Anti-9V OPA Titers, PRE (N= 0, 0, 0, 87)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	398.2 (253.8 to 624.9)
Anti-9V OPA Titers, D7 (N=201, 13, 51, 93)	9419.4 (7586 to 11695.9)	12234.7 (8280.5 to 18077.3)	7730.3 (5361.8 to 11145.2)	8322.7 (6605.7 to 10486.1)
Anti-9V OPA Titers, M3 (N= 0, 0, 0, 94)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	6456.1 (5458.1 to 7636.6)
Anti-14 OPA Titers, PRE (N= 0, 0, 0, 83)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	586.5 (439 to 783.6)
Anti-14 OPA Titers, D7 (N= 197, 13, 51, 94)	8572.3 (7145.4 to 10284.3)	4192.8 (2218.6 to 7923.7)	6883.1 (5057.3 to 9368)	4678.2 (3788 to 5777.5)
Anti-14 OPA Titers, M3 (N= 0, 0, 0, 95)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	4891.1 (4178.8 to 5724.8)
Anti-18C OPA Titers, PRE (N= 0, 0, 0, 89)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	5.3 (4.2 to 6.6)
Anti-18C OPA Titers, D7 (N= 194, 13, 50, 92)	3378.9 (2652.2 to 4304.8)	3478.6 (1788.5 to 6765.8)	1663.2 (970.5 to 2850.2)	2503.1 (1692.6 to 3701.6)
Anti-18C OPA Titers, M3 (N= 0, 0, 0, 92)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	2255.9 (1876.9 to 2711.4)
Anti-19F OPA Titers, PRE (N= 0, 0, 0, 92)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	12 (8.3 to 17.5)
Anti-19F OPA Titers, D7 (N= 196, 13, 50, 93)	1346.4 (1068.6 to 1696.5)	2340.4 (654.8 to 8365.2)	662.3 (430 to 1020.1)	700.2 (456.1 to 1074.9)
Anti-19F OPA Titers, M3 (N= 0, 0, 0, 93)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	1437.7 (1146.9 to 1802.3)
Anti-23F OPA Titers, PRE (N= 0, 0, 0, 83)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	176.4 (83.4 to 373.2)
Anti-23F OPA Titers, D7 (N= 199, 13, 50, 96)	8700.4 (7021.7 to 10780.5)	11341.1 (5374.6 to 23931)	7871.9 (4965.3 to 12480.1)	6813.9 (5249.5 to 8844.6)
Anti-23F OPA Titers, M3 (N= 0, 0, 0, 95)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	5586.1 (4666.1 to 6687.5)

No statistical analyses for this end point

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

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End point title

Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

End point description

The seropositivity cut-off for the assay was ≥ 0.05 μg/mL. Antibody concentrations against 6A and 19A pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micrograms per milliliter (µg/mL).

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	390	31	102
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-6A antibodies, Y1 (N= 390, 31, 102)	0.28 (0.24 to 0.32)	0.44 (0.28 to 0.7)	0.27 (0.21 to 0.36)
Anti-19A antibodies, Y1 (N= 390, 31, 102)	0.28 (0.25 to 0.32)	0.21 (0.13 to 0.33)	0.23 (0.17 to 0.3)

No statistical analyses for this end point

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) – Follow-Up Period: Persistence analysis in Year 2 (111346 sub-study)

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End point title

Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) – Follow-Up Period: Persistence analysis in Year 2 (111346 sub-study)

End point description

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PDDIT- 007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	368	30	96
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-6A antibodies, Y2 (N= 368, 30, 96)	0.33 (0.28 to 0.4)	0.57 (0.3 to 1.11)	0.4 (0.27 to 0.58)
Anti-19A antibodies, Y2 (N= 368, 30, 96)	0.37 (0.31 to 0.44)	0.25 (0.14 to 0.44)	0.35 (0.25 to 0.5)

No statistical analyses for this end point

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

Antibody concentrations against 6A and 19A pneumococcal serotypes were determined as Geometric Mean Antibody Concentrations (GMC) and expressed as micro grams per milliliter (µg/mL). The seropositivity cut-off for the assay was ≥ 0.05 μg/mL.

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administrated in study 10PN-PD-DIT- 007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	264	19	75
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-6A antibodies, Y4 (N= 263, 19, 74)	0.92 (0.77 to 1.1)	0.69 (0.34 to 1.38)	0.75 (0.55 to 1.03)
Anti-19A antibodies, Y4 (N= 263, 19, 75)	1.3 (1.07 to 1.59)	1.08 (0.5 to 2.33)	1.14 (0.77 to 1.68)

No statistical analyses for this end point

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and 19A) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and 19A) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	210	14	55	98
Units: μg/mL
geometric mean (confidence interval 95%)
Anti-6A antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.2 (0.15 to 0.27)
Anti-6A antibodies, D7 (N= 208, 14, 55, 98)	2.2 (1.85 to 2.6)	1.67 (1 to 2.8)	1.33 (0.96 to 1.83)	0.44 (0.33 to 0.58)
Anti-6A antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.92 (0.73 to 1.16)
Anti-19A antibodies, PRE (N= 0, 0, 0, 97)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0.44 (0.32 to 0.6)
Anti-19A antibodies, D7 (N= 208, 14, 54, 98)	2.79 (2.33 to 3.35)	2.44 (1.2 to 4.96)	1.72 (1.14 to 2.61)	1.1 (0.84 to 1.45)
Anti-19A antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	2.39 (1.9 to 3.01)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

End point description

Opsonophagocytic activity were assessed for pneumococcal serotypes 6A and 19A (OPA-6A and OPA-19A). The seropositivity cut-off for the assay was ≥ 8. Opsonophagocytic activity was expressed as Geometric Mean Antibody Titers (GMT).

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	352	26	93
Units: Titers
geometric mean (confidence interval 95%)
Anti-6A OPA Titers, Y1 (N= 323, 25, 75)	59 (45.9 to 76)	610.2 (317.7 to 1171.9)	46.6 (28.3 to 76.8)
Anti-19A OPA Titers, Y1 (N= 155, 26, 93)	6 (5.2 to 6.8)	5.9 (3.7 to 9.5)	5.5 (4.5 to 6.8)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

End point description

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	351	27	91
Units: Titers
geometric mean (confidence interval 95%)
Anti-6A OPA Titers, Y2 (N= 314, 25, 82)	121.8 (95.2 to 156)	356.5 (134.6 to 944.6)	133.7 (81.8 to 218.7)
Anti-19A OPA Titers, Y2 (N= 351, 27, 91)	12.8 (10.4 to 15.7)	10.9 (5.2 to 22.8)	11.1 (7.6 to 16.2)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	251	16	71
Units: Titers
geometric mean (confidence interval 95%)
Anti-6A OPA Titers, Y4 (N= 231, 14, 66)	213.5 (165.4 to 275.7)	227.8 (72.1 to 720)	153.5 (90.5 to 260.2)
Anti-19A OPA Titers, Y4 (N= 246, 15, 68)	31.2 (23.6 to 41.3)	14.3 (5.6 to 36.8)	21.8 (13.3 to 35.7)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	201	13	50	92
Units: Titers
geometric mean (confidence interval 95%)
Anti-6A OPA Titers, PRE (N= 0, 0, 0, 82)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	102.6 (61.5 to 171.2)
Anti-6A OPA Titers, D7 (N= 189, 12, 49, 90)	1217.7 (957.8 to 1548.2)	1490.2 (681.6 to 3257.8)	467.7 (293.8 to 744.5)	826.5 (593.9 to 1150.2)
Anti-6A OPA Titers, M3 (N= 0, 0, 0, 91)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	943.4 (691.3 to 1287.4)
Anti-19A OPA Titers, PRE (N= 0, 0, 0, 92)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	9.9 (7 to 13.8)
Anti-19A OPA Titers, D7 (N= 194, 13, 48, 90)	467 (335 to 651.1)	437.6 (81.3 to 2356.3)	106.1 (54.1 to 208.3)	431.2 (269.4 to 689.9)
Anti-19A OPA Titers, M3 (N= 0, 0, 0, 91)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	376.4 (256.3 to 552.6)

No statistical analyses for this end point

Secondary: Antibody concentrations to protein D (Anti-PD) - Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)

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End point title

Antibody concentrations to protein D (Anti-PD) - Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)

End point description

Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL.

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	390	30	102
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD antibodies, Y1 (N= 390, 30, 102)	822.1 (731.5 to 923.9)	93.9 (66.6 to 132.3)	193.6 (155.9 to 240.4)

No statistical analyses for this end point

Secondary: Antibody concentrations to protein D (Anti-PD) – Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)

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End point title

Antibody concentrations to protein D (Anti-PD) – Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)

End point description

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT- 007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	368	29	96
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD antibodies, Y2 (N= 368, 29, 96)	573.2 (509.6 to 644.8)	116.7 (80.9 to 168.3)	157.5 (128.7 to 192.8)

No statistical analyses for this end point

Secondary: Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT- 007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	264	19	75
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD antibodies, Y4 (N= 261, 19, 74)	372.4 (329.6 to 420.9)	144.9 (86.3 to 243.2)	161.4 (128.4 to 203)

No statistical analyses for this end point

Secondary: Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	208	14	54	98
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD antibodies, PRE (N= 0, 0, 0, 95)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	106 (91.1 to 123.4)
Anti-PD antibodies, D7 (N= 208, 14, 54, 98)	2106 (1806.7 to 2454.9)	718.2 (442.5 to 1165.7)	680.7 (522.9 to 886.2)	382.9 (320.7 to 457.2)
Anti-PD antibodies, M3 (N= 0, 0, 0, 98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	708.6 (604.6 to 830.4)

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local symptoms

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End point title

Number of subjects reported with solicited local symptoms

End point description

Solicited local symptoms assessed were pain, redness and swelling. Any occurrence of symptom regardless of intensity grade. Any Redness or any Swelling symptom = any symptom greater than (>) 0 millimeter (mm). Grade 3 pain = maximum intensity of local injection defined as subject crying when limb was moved/spontaneously painful. Grade 3 redness/swelling= maximum intensity of local injection >30 mm. Follow-up period was of 4 days (Days 0-3) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study, thus one period of 4 days for primed subjects and 2 periods of 4 days for unprimed subjects.

End point type

Secondary

End point timeframe

Within 4 days (Days 0-3) period(s) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	264	20	64	100
Units: Participants
Pain, Any (N= 264, 20, 64, 100)	157	9	34	54
Redness, Any (N= 264, 20, 64, 100)	90	5	14	21
Swelling, Any (N= 264, 20, 64, 100)	67	4	15	20
Pain, Grade 3 (N= 264, 20, 64, 100)	7	1	5	3
Redness, Grade 3 (> 30 mm) (N= 264, 20, 64, 100)	7	0	0	1
Swelling, Grade 3 (> 30 mm) (N= 264, 20, 64, 100)	5	0	1	2

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited general symptoms

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End point title

Number of subjects reported with solicited general symptoms

End point description

Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (any fever defined as temperature by axillary measurement of 37.5°C and above). Grade 3 drowsiness was defined as drowsiness that prevented normal activity; Grade 3 irritability was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as subject not eating at all. Grade 3 fever was defined as axillary temperature >39.5°C. Related AE was defined as any AE assessed by investigators to be causally related to administration of the study vaccine. Follow-up period was of 4 days (Days 0-3) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study, thus one period of 4 days for primed subjects and 2 periods of 4 days for unprimed subjects.

End point type

Secondary

End point timeframe

Within 4 days (Days 0-3) period(s) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	263	20	64	100
Units: Participants
Drowsiness, Any (N= 263, 20, 64, 100)	49	2	12	12
Drowsiness, Grade 3 (N= 263, 20, 64, 100)	1	0	0	0
Drowsiness, Related (N= 263, 20, 64, 100)	48	2	11	11
Irritability, Any (N= 263, 20, 64, 100)	35	4	6	8
Irritability, Related (N= 263, 20, 64, 100)	35	4	6	8
Irritability, Grade 3 (N= 263, 20, 64, 100)	0	0	0	0
Loss of appetite, Any (N= 263, 20, 64, 100)	30	3	6	13
Loss of appetite, Grade 3 (N= 263, 20, 64, 100)	1	0	1	0
Loss of appetite, Related (N= 263, 20, 64, 100)	30	3	5	11
Fever, Any (N= 263, 20, 64, 100)	13	0	2	5
Fever, >39,5°C (N= 263, 20, 64, 100)	0	0	0	0
Fever, Related (N= 263, 20, 64, 100)	13	0	1	5

No statistical analyses for this end point

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

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End point title

Number of subjects with unsolicited adverse events (AEs)

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. Follow-up period was of 31 days (Days 0-30) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study, thus one period of 31 days for primed subjects and 2 periods of 31 days for unprimed subjects.

End point type

Secondary

End point timeframe

Within 31 days (Day 0-30) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	264	20	65	100
Units: Participants
Any Unsolicited AEs (N= 264, 20, 65, 100)	25	0	3	6

No statistical analyses for this end point

Secondary: Number of subjects with serious adverse events (SAEs) related to study procedures [Follow-up Period: Year 1 (111345 sub-study)]

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End point title

Number of subjects with serious adverse events (SAEs) related to study procedures [Follow-up Period: Year 1 (111345 sub-study)]

End point description

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. “Any” was defined an incidence of a SAE regardless of intensity/severity.

End point type

Secondary

End point timeframe

During Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007) i.e. for each primed subject: from the time the subject was enrolled in the 111345 study until he/she completed the same study (approximatively 12 months)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	391	31	102
Units: Participants
Any Related SAEs, Y1 (N=391, 31, 102)	1	0	0

No statistical analyses for this end point

Secondary: Number of subjects with serious adverse events (SAEs) related to study procedures [(Follow-up Period: Year 2 (111346 sub-study) until Year 4 (111347 sub-study)]

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End point title

Number of subjects with serious adverse events (SAEs) related to study procedures [(Follow-up Period: Year 2 (111346 sub-study) until Year 4 (111347 sub-study)]

End point description

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. “Any” is defined an incidence of a SAE regardless of intensity/severity.

End point type

Secondary

End point timeframe

From Year (Y) 2 to Y4 FU visit (post booster vaccination administered in 10PN-PD-DIT-007) i.e. for each subject(S): when S was enrolled in 111346 study until S completed the same study visit or the 111347 study visit (range of 1 to 3 years for each S))

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	370	31	96
Units: Participants
Any Related SAEs, Y2 to Y4, (N= 370, 31, 96)	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects with serious adverse events (SAEs) [Follow-up Period: Vaccination Period in Year 4 (111347 sub-study)]

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End point title

Number of subjects with serious adverse events (SAEs) [Follow-up Period: Vaccination Period in Year 4 (111347 sub-study)]

End point description

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. “Any” is defined an incidence of a SAE regardless of intensity/severity.

End point type

Secondary

End point timeframe

For primed groups: from Months 48-49 (additional vaccination period); for unprimed group: from Day 0 up to Month 3 (catch-up vaccination period)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	264	20	65	100
Units: Participants
Any Related SAEs, Y4 (N= 264, 20, 65, 100)	0	0	0	0

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The seropositivity cut-off for the assay was 8.

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	359	27	94
Units: Participants
Anti-1 OPA, Y1 (N= 354, 27, 92)	188	2	26
Anti-4 OPA, Y1 ( N= 340, 26, 86)	201	21	65
Anti-5 OPA, Y1 (N= 335, 27, 89	241	2	46
Anti-6B OPA, Y1 (N= 354, 25, 88)	164	23	44
Anti-7F OPA, Y1 (N= 346, 25, 89)	343	20	85
Anti-9V OPA, Y1 (N= 352, 26, 94)	351	26	90
Anti-14 OPA, Y1 (N= 343, 25, 91)	336	25	89
Anti-18C OPA, Y1 (N= 319, 24, 84)	173	10	25
Anti-19F OPA, Y1 (N= 359, 27, 93)	306	19	83
Anti-23F OPA, Y1 (N=336, 27, 93)	301	26	82

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: persistence analysis in Year 2 (111346 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: persistence analysis in Year 2 (111346 sub-study)]

End point description

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	354	27	92
Units: Participants
Anti-1 OPA, Y2 (N= 354, 27, 92)	92	0	15
Anti-4 OPA, Y2 (N= 335, 27, 84)	146	12	48
Anti-5 OPA, Y2 (N= 351, 27, 91)	169	2	31
Anti-6B OPA, Y2 (N= 342, 27, 88)	241	24	67
Anti-7F OPA Titers, Y2 (N= 350, 27, 91)	350	26	90
Anti-9V OPA, Y2 (N= 349, 27, 92)	247	27	87
Anti-14 OPA, Y2 (N= 341, 25, 90)	333	24	85
Anti-18C OPA, Y2 (N= 325, 27, 83)	165	11	29
Anti-19F OPA, Y2 (N= 349, 27, 92)	279	21	78
Anti-23F OPA, Y2 (N= 342, 26, 91)	285	25	72

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	250	16	72
Units: Participants
Anti-1 OPA, Y4 (N= 250, 16, 72)	55	1	17
Anti-4 OPA, Y4 (N= 232, 16, 63)	107	8	33
Anti-5 OPA, Y4 (N= 243, 15, 68)	80	2	11
Anti-6B OPA, Y4 (N= 250, 16, 68)	223	15	62
Anti-7F OPA, Y4 (N= 249, 15, 71)	248	15	71
Anti-9V OPA, Y4 (N= 250, 15, 70)	242	14	68
Anti-14 OPA, Y4 (N= 250, 15, 71)	247	14	70
Anti-18C OPA, Y4 (N= 226, 16, 63)	121	8	27
Anti-19F OPA, Y4 (N= 247, 16, 69)	211	14	62
Anti-23F OPA, Y4 (N= 239, 15, 65)	209	15	55

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsophagocytic activity against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for opsophagocytic activity against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	201	13	51	96
Units: Participants
Anti-1 OPA, PRE (N= 0, 0, 0, 94)	0	0	0	8
Anti-1 OPA, D7 (N= 197, 13, 50, 92)	193	13	48	90
Anti-1 OPA, M3 (N= 0, 0, 0, 95)	0	0	0	87
Anti-4 OPA, PRE (N= 0, 0, 0, 81)	0	0	0	17
Anti-4 OPA, D7 (N= 196, 13, 51, 93)	194	13	50	93
Anti-4 OPA, M3 (N= 0, 0, 0, 94)	0	0	0	94
Anti-5 OPA, PRE (N= 0, 0, 0, 92)	0	0	0	8
Anti-5 OPA, D7 (N= 193, 13, 48, 91)	186	13	47	87
Anti-5 OPA, M3 (N= 0, 0, 0, 92)	0	0	0	89
Anti-6B OPA, PRE (N= 0, 0, 0, 79)	0	0	0	35
Anti-6B OPA, D7 (N= 198, 13, 50, 93)	196	13	48	84
Anti-6B OPA, M3 (N= 0, 0, 0, 95)	0	0	0	94
Anti-7F OPA, PRE (N= 0, 0, 0, 74)	0	0	0	67
Anti-7F OPA, D7 (N= 199, 13, 50, 93)	199	13	50	93
Anti-7F OPA, M3 (N= 0, 0, 0, 93)	0	0	0	93
Anti-9V OPA, PRE (N= 0, 0, 0, 87)	0	0	0	87
Anti-9V OPA, D7 (N= 201, 13, 51, 93)	201	13	51	93
Anti-9V OPA, M3 (N= 0, 0, 0, 94)	0	0	0	94
Anti-14 OPA, PRE (N= 0, 0, 0, 83)	0	0	0	81
Anti-14 OPA, D7 (N= 197, 13, 51, 94)	197	13	51	94
Anti-14 OPA, M3 (N= 0, 0, 0, 95)	0	0	0	95
Anti-18C OPA, PRE (N= 0, 0, 0, 89)	0	0	0	7
Anti-18C OPA, D7 (N= 194, 13, 50, 92)	190	13	48	88
Anti-18C OPA, M3 (N= 0, 0, 0, 92)	0	0	0	92
Anti-19F OPA, PRE (N= 0, 0, 0, 92)	0	0	0	30
Anti-19F OPA, D7 (N= 196, 13, 50, 93)	194	13	50	91
Anti-19F OPA, M3 (N= 0, 0, 0, 93)	0	0	0	93
Anti-23F OPA, PRE (N= 0, 0, 0, 83)	0	0	0	47
Anti-23F OPA, D7 (N= 199, 13, 50, 96)	197	13	49	95
Anti-23F OPA, M3 (N= 0, 0, 0, 95)	0	0	0	95

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: persistence analysis in Year 1 (111345 sub-study)]

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End point title

Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: persistence analysis in Year 1 (111345 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The results for the immune responses were measured by 22F-inhibition ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	390	31	102
Units: Participants
Anti-6A antibodies, Y1 (N= 390, 31, 102)	376	31	97
Anti-19A antibodies, Y1 (N= 390, 31, 102)	366	29	93

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

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End point title

Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by 22F-inhibation ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	368	30	96
Units: Participants
Anti-6A antibodies, Y2 (N= 368, 30, 96)	330	30	86
Anti-19A antibodies, Y2 (N= 368, 30, 96)	319	25	83

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by 22F-inhibition ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	263	19	75
Units: Participants
Anti-6A antibodies, Y4 (N= 263, 31, 75)	256	18	72
Anti-19A antibodies, Y4 (N= 263, 31, 75)	260	18	74

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by 22F-inhibition ELISA. The seropositivity cut-off for the assay was 0.05 μg/mL.

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	208	14	54	98
Units: Participants
Anti-6A antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	76
Anti-6A antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	92
Anti-6A antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	97
Anti-19A antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	88
Anti-19A antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	97
Anti-19A antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were mesured by Opsonophagocytic activity (OPA). The seropositivity cut-off for the assay was 8.

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	352	26	93
Units: Participants
Anti-6A OPA, Y1 (N= 323, 25, 75)	196	24	45
Anti-19A OPA, Y1 (352, 26, 93)	45	3	10

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 2 (111346 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 2 (111346 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by Opsonophagocytic activity (OPA). The seropositivity cut-off for the assay was 8.

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	351	27	91
Units: Participants
Anti-6A OPA, Y2 (N= 314, 25, 82)	235	21	62
Anti-19A OPA, Y2 (N= 351, 27, 91)	115	8	29

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by Opsonophagocytic Activity (OPA). The seropositivity cut-off for the assay was 8.

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	246	15	68
Units: Participants
Anti-6A OPA Titers, Y4 (N= 231, 14, 66)	194	12	51
Anti-19A OPA Titers, Y4 (N= 246, 15, 68)	135	7	34

No statistical analyses for this end point

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Pneumococcal serotypes assessed were 6A and 19A. The immune responses were measured by Opsonophagocytic Activity (OPA). The seropositivity cut-off for the assay was 8.

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	194	13	49	92
Units: Participants
Anti-6A OPA, PRE (N= 0, 0, 0, 82)	0	0	0	57
Anti-6A OPA, D7 (N= 189, 12, 49, 92)	185	12	46	88
Anti-6A OPA, M3 (N= 0, 0, 0, 91)	0	0	0	87
Anti-19A OPA, PRE (N= 0, 0, 0, 92)	0	0	0	25
Anti-19A OPA, D7 (N= 194, 13, 48, 90)	173	11	36	81
Anti-19A OPA, M3 (N= 0, 0, 0, 91)	0	0	0	87

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-protein D (Anti-PD) [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

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End point title

Number of seropositive subjects for anti-protein D (Anti-PD) [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

End point description

A seropositive subject was a subject whose anti-PD antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.

End point type

Secondary

End point timeframe

At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	390	30	102
Units: Participants
Anti-PD antibodies, Y1 (N= 390, 30, 102)	373	11	71

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti protein D (Anti-PD) [Follow-up Period: Persistence analysis in Year 2 (111345 sub-study)]

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End point title

Number of seropositive subjects for anti protein D (Anti-PD) [Follow-up Period: Persistence analysis in Year 2 (111345 sub-study)]

End point description

A seropositive subject was a subject whose anti-PD antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.

End point type

Secondary

End point timeframe

At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	368	29	96
Units: Participants
Anti-PD antibodies, Y2 (N= 368, 29, 96)	340	15	65

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for anti-protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

End point description

A seropositive subject was a subject whose anti-PD antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.

End point type

Secondary

End point timeframe

At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Number of subjects analysed	261	19	74
Units: Participants
Anti-PD antibodies, Y4 (N= 261, 19, 74)	241	12	54

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for anti-protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

End point description

A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. The seropositivity cut-off for the assay was 100 EL.U/ML.

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	208	14	54	98
Units: Participants
Anti-PD antibodies, PRE (N= 0, 0, 0, 95)	0	0	0	54
Anti-PD antibodies, D7 (N= 208, 14, 54, 96)	207	14	45	92
Anti-PD antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98

No statistical analyses for this end point

Secondary: Number of seropositive subjects for anti-vaccine pneumococcal serotypes antibodies [Follow-up Period: Immunogenicity analysis in Year 4 (111347 sub-study)]

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End point title

Number of seropositive subjects for anti-vaccine pneumococcal serotypes antibodies [Follow-up Period: Immunogenicity analysis in Year 4 (111347 sub-study)]

End point description

End point type

Secondary

End point timeframe

End point values	Synflorix + Infanrix + Havrix and/or Varilrix Group	Prevenar + Infanrix + Havrix and/or Varilrix Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix	Unprimed Group
Number of subjects analysed	208	14	54	98
Units: Participants
Anti-1 antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	69
Anti-1 antibodies, D7 (N= 208, 14, 54, 98)	207	14	54	97
Anti-1 antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-4 antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	29
Anti-4 antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	98
Anti-4 antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-5 antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	72
Anti-5 antibodies, D7 (N= 208, 14, 54, 98)	207	14	54	98
Anti-5 antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-6B antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	77
Anti-6B antibodies, D7 (N= 208, 14, 54, 97)	207	14	54	94
Anti-6B antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-7F antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	64
Anti-7F antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	98
Anti-7F antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-9V antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	67
Anti-9V antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	94
Anti-9V antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-14 antibodies, PRE (N= 0, 0, 0, 96)	0	0	0	90
Anti-14 antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	97
Anti-14 antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-18C antibodies, PRE (N= 0, 0, 0, 96)	0	0	0	52
Anti-18C antibodies, D7 (N= 208, 14, 54, 98)	207	14	54	97
Anti-18C antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-19F antibodies, PRE (N= 0, 0, 0, 96)	0	0	0	75
Anti-19F antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	97
Anti-19F antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98
Anti-23F antibodies, PRE (N= 0, 0, 0, 97)	0	0	0	98
Anti-23F antibodies, D7 (N= 208, 14, 54, 98)	208	14	54	90
Anti-23F antibodies, M3 (N= 0, 0, 0, 98)	0	0	0	98

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited, Unsolicited AEs: within 4 days and 31 days post-vacc. for subjects from Y4 FU period. SAEs related to study procedure: at Y1, from Y2 to Y4 for primed subjects. Any SAEs: during Y4 vac. period (primed subj.: M 48-49; unprimed subj.: M 0-3).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

Prevenar + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Synflorix + Infanrix + Havrix and/or Varilrix Group

Reporting group description

Reporting group title

Unprimed Group

Reporting group description

Reporting group title

Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix

Reporting group description

Serious adverse events	Prevenar + Infanrix + Havrix and/or Varilrix Group	Synflorix + Infanrix + Havrix and/or Varilrix Group	Unprimed Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 31 (0.00%)	1 / 391 (0.26%)	0 / 100 (0.00%)	0 / 102 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Infections and infestations
Broncopneumonia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 31 (0.00%)	1 / 391 (0.26%)	0 / 100 (0.00%)	0 / 102 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Prevenar + Infanrix + Havrix and/or Varilrix Group	Synflorix + Infanrix + Havrix and/or Varilrix Group	Unprimed Group	Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
Total subjects affected by non serious adverse events
subjects affected / exposed	12 / 31 (38.71%)	188 / 391 (48.08%)	65 / 100 (65.00%)	39 / 102 (38.24%)
General disorders and administration site conditions
Pain
subjects affected / exposed ^[1]	9 / 20 (45.00%)	157 / 264 (59.47%)	54 / 100 (54.00%)	34 / 64 (53.13%)
occurrences all number	9	157	54	34
Redness
subjects affected / exposed ^[2]	5 / 20 (25.00%)	90 / 264 (34.09%)	21 / 100 (21.00%)	14 / 64 (21.88%)
occurrences all number	5	90	21	14
Swelling
subjects affected / exposed ^[3]	4 / 20 (20.00%)	67 / 264 (25.38%)	20 / 100 (20.00%)	15 / 64 (23.44%)
occurrences all number	4	67	20	15
Drowsiness
subjects affected / exposed ^[4]	2 / 20 (10.00%)	49 / 263 (18.63%)	12 / 100 (12.00%)	12 / 64 (18.75%)
occurrences all number	2	49	12	12
Irritability
subjects affected / exposed ^[5]	4 / 20 (20.00%)	35 / 263 (13.31%)	8 / 100 (8.00%)	6 / 64 (9.38%)
occurrences all number	4	35	8	6
Loss of appetite
subjects affected / exposed ^[6]	3 / 20 (15.00%)	30 / 263 (11.41%)	13 / 100 (13.00%)	6 / 64 (9.38%)
occurrences all number	3	30	13	6
Fever (Axillary temperature ≥ 37.5°C)
subjects affected / exposed ^[7]	0 / 20 (0.00%)	13 / 263 (4.94%)	5 / 100 (5.00%)	2 / 64 (3.13%)
occurrences all number	0	13	5	2

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for solicited symptoms post vaccination was done solely on subjects participating to the Immunological Memory phase of the 111347 study, on subjects with results available for the specified symptom.

More information

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Were there any global substantial amendments to the protocol? Yes

22 Jun 2010

Amendment 1 Some aspects of study design, endpoints and study conclusion regarding the immunological memory and assessment of immune response following a second-dose of the vaccine have been added for the clarity of the study.

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

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Clinical trials

Clinical Trial Results: Assessment of long-term antibody persistence and immunological memory in children previously vaccinated with four pneumococcal conjugate vaccine doses and assessment of pneumococcal catch-up vaccination with GSK1024850A at 5 years of age.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations greater than or equal to (≥) the cut-off [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations greater than or equal to (≥) the cut-off [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Primary: Number of subjects with anti-vaccine pneumococcal serotypes antibody concentrations ≥ the cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 1 (111345 sub-study)]

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) – Follow-Up Period: Persistence analysis in Year 2 (111346 sub-study)

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) – Follow-Up Period: Persistence analysis in Year 2 (111346 sub-study)

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and 19A) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations against cross-reactive pneumococcal serotypes 6A and 19A (Anti-6A and 19A) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against crossreactive pneumococcal serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations to protein D (Anti-PD) - Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)

Secondary: Antibody concentrations to protein D (Anti-PD) - Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)

Secondary: Antibody concentrations to protein D (Anti-PD) – Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)

Secondary: Antibody concentrations to protein D (Anti-PD) – Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)

Secondary: Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Antibody concentrations to protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited local symptoms

Secondary: Number of subjects reported with solicited general symptoms

Secondary: Number of subjects reported with solicited general symptoms

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

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

Secondary: Number of subjects with serious adverse events (SAEs) related to study procedures [Follow-up Period: Year 1 (111345 sub-study)]

Secondary: Number of subjects with serious adverse events (SAEs) related to study procedures [Follow-up Period: Year 1 (111345 sub-study)]

Secondary: Number of subjects with serious adverse events (SAEs) related to study procedures [(Follow-up Period: Year 2 (111346 sub-study) until Year 4 (111347 sub-study)]

Secondary: Number of subjects with serious adverse events (SAEs) related to study procedures [(Follow-up Period: Year 2 (111346 sub-study) until Year 4 (111347 sub-study)]

Secondary: Number of subjects with serious adverse events (SAEs) [Follow-up Period: Vaccination Period in Year 4 (111347 sub-study)]

Secondary: Number of subjects with serious adverse events (SAEs) [Follow-up Period: Vaccination Period in Year 4 (111347 sub-study)]

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence analysis in Year 1 (111345 sub-study)]

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: persistence analysis in Year 2 (111346 sub-study)]

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: persistence analysis in Year 2 (111346 sub-study)]

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Number of seropositive subjects for opsonophagocytic activity against pneumococcal serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 sub-study)]

Secondary: Number of seropositive subjects for opsophagocytic activity against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Number of seropositive subjects for opsophagocytic activity against pneumococcal serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 sub-study)]

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: persistence analysis in Year 1 (111345 sub-study)]

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: persistence analysis in Year 1 (111345 sub-study)]

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

Secondary: Number of seropositive subjects for anti-pneumococcal cross-reactive serotypes 6A and 19A [Follow-up Period: Persistence analysis in Year 2 (111346 sub-study)]

Clinical Trial Results:
Assessment of long-term antibody persistence and immunological memory in children previously vaccinated with four pneumococcal conjugate vaccine doses and assessment of pneumococcal catch-up vaccination with GSK1024850A at 5 years of age.