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Clinical Trial Results:
A phase II, randomized, controlled, observer-blind study to assess the safety, reactogenicity and immunogenicity of two formulations of GlaxoSmithKline (GSK) Biologicals’ Streptococcus pneumoniae protein containing vaccine given as a 3-dose primary vaccination course co-administered with DTPa-HBV-IPV/Hib* vaccine during the first 6 months of life and as a booster dose at 12-15 months of age. *DTPa-HBV-IPV/Hib = Infanrix hexa™

Summary
EudraCT number	2010-019730-27
Trial protocol	CZ PL SE DE
Global end of trial date	01 Oct 2012

Results information
Results version number	v3(current)
This version publication date	02 Jun 2019
First version publication date	04 Apr 2015
Other versions	v1 , v2
Version creation reason	New data added to full data set additional OPA-19A results for primary and booster phase

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

113994

ISRCTN number

US NCT number

NCT01204658

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l'Institut 89, Rixensart, Belgium,

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089904466, GSKClinicalSupportHD@gsk.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

16 Nov 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Oct 2012

Was the trial ended prematurely?

Main objective of the trial

1.Non-inferiority of the candidate pneumococcal vaccine (dPly-Low Dose [LD] and PhtD-LD)[10PP-LD] versus Synflorix™ vaccine when administered with Infanrix hexa™ (DTPa-HBV-IPV/Hib) as a 3-dose primary vaccination, in terms of post-primary immunization fever > 40.0°C (rectal temperature) with causal relationship to vaccination. 2.(sequential): Non-inferiority of the candidate pneumococcal vaccine (dPly-High Dose [HD] and PhtD-HD)[10PP-HD] versus Synflorix™ vaccine when administered with Infanrix hexa™ as a 3-dose primary vaccination, in terms of post-primary immunization fever > 40.0°C (rectal temperature) with causal relationship to vaccination. Criteria = Non-inferiority supported if one can rule out an increase, in terms of percentage of subjects with fever >40.0°C with causal relationship to vaccination (10PP-LD or 10PP-HD group as compared to Synflorix™ group) above 5% + half the incidence in the control group (= null hypothesis) as shown by a one-sided P-value < 5%.

Protection of trial subjects

GSK has monitored the study to verify that, amongst others, the: • Data are authentic, accurate, and complete. • Safety and rights of subjects are being protected. • Study is conducted in accordance with the currently approved protocol and any amendments, any other study agreements, GCP and all applicable regulatory requirements. All subjects were supervised after vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Only eligible subjects that had no contraindications to any components of the vaccines were vaccinated. Subjects were followed-up for 31 days after each/last vaccination.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Sep 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 110

Country: Number of subjects enrolled

Sweden: 22

Country: Number of subjects enrolled

Czech Republic: 434

Country: Number of subjects enrolled

Germany: 10

Worldwide total number of subjects

576

EEA total number of subjects

576

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)

576

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

A total of 576 subjects were initially enrolled in the study. Of these, one subject was older than protocol defined age range for the first vaccination, and therefore did not receive any vaccination.

Screening details

The study duration is approximately 10 to 14 months depending on age at recruitment and age at booster vaccination. 2 Phases in the study: Primary Phase when subjects received a 3-dose of pneumococcal vaccine co-administered with Infanrix hexa™ (Months 0, 1, 2), and Booster Phase when subjects received one dose of the same vaccines (Month 10).

Number of subjects started

576

Number of subjects completed

575

Reason: Number of subjects

Study vaccine dose not administrated: 1

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Assessor

Blinding implementation details

Data collected in an observer-blind manner, meaning that during the course of the study, the subject and those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity, and immunogenicity) will all be unaware of which vaccine was administered. To do so, vaccine preparation and administration will be done by authorised medical personnel who will not participate in any of the study clinical evaluation assays. The laboratory will be blinded to the treatment.

Are arms mutually exclusive

Yes

10PP-LD/Infanrix hexa Group

Arm description

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of the GSK 2189242A (or 10PP) vaccine combined with low doses (LD) of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD) co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10.

Arm type

Experimental

Investigational medicinal product name

Pneumococcal vaccine GSK 2189242A (Low Dose formulation 1)

Investigational medicinal product code

GSK 2189242A LD

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

4 doses: 3 primary doses at Study Months 0, 1 and 2. Subjects also received a booster dose , administered at Study Month 10. The 3 primary doses of the 10PP vaccine were administered intramuscularly (IM) in the thigh, on the right side. Booster doses were administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side for the 10PP vaccine.

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

DTPa-HBV-IPV/Hib

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

4 doses: 3 primary doses at Study Months 0, 1 and 2. Subjects also received a booster dose , administered at Study Month 10. The 3 primary doses of the Infanrix hexa™ vaccines were administered intramuscularly (IM) in the thigh, on the left side. Booster dose was administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the right side.

10PP-HD/Infanrix hexa Group

Arm description

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of the GSK 2189242A (or 10PP) vaccine combined with high doses (HD) of pneumococcal pneumolysin toxoid proteins (dPly) and pneumococcal histidine protein D (PhtD), co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10.

Arm type

Experimental

Investigational medicinal product name

Pneumococcal vaccine (High Dose formulation 2)

Investigational medicinal product code

GSK 2189242A HD

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

4 doses: 3-dose primary vaccination at Study Months 0, 1 and 2 and a booster dose administered at Study Month 10.The 3 primary doses of the 10PP vaccine were administered intramuscularly (IM) in the thigh, on the right side. Booster dose was administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side.

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

DTPa-HBV-IPV/Hib

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Synflorix/Infanrix hexa Group

Arm description

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of Synflorix™ vaccine, co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10.

Arm type

Active comparator

Investigational medicinal product name

Synflorix™

Investigational medicinal product code

10Pn-PD-DiT

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

4 doses: 3-dose primary vaccination at Study Months 0, 1 and 2 and a booster dose administered at Study Month 10. The 3 primary doses of Synflorix™ vaccine were administered intramuscularly (IM) in the thigh, on the right side. Booster dose was administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side.

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

DTPa-HBV-IPV/Hib

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Prevnar 13/Infanrix hexa Group

Arm description

This group consisted in infants aged 6-14 weeks at primary vaccination who received a 3-dose primary vaccination of Prevnar 13™ vaccine, co-administered with the Infanrix hexa™ vaccine at Study Months 0, 1 and 2. Subjects also received a booster dose of each of these vaccines, administered at Study Month 10.

Arm type

Active comparator

Investigational medicinal product name

Prevenar 13™

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

4 doses: 3-dose primary vaccination of Prevnar 13™ vaccine at Study Months 0, 1 and 2 and a booster dose , administered at Study Month 10. The 3 primary doses of Prevnar 13™ were administered intramuscularly (IM) in the thigh, on the right side. Booster dose was administered IM into the deltoid or thigh if the deltoid muscle size was not adequate, on the left side.

Investigational medicinal product name

Infanrix hexa™

Investigational medicinal product code

DTPa-HBV-IPV/Hib

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 1 ^[1]	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Started	146	142	145	142
Completed	144	140	140	140
Not completed	2	2	5	2
Consent withdrawn by subject	-	1	1	2
Adverse event, non-fatal	-	1	2	-
Migrated/moved from study area	2	-	2	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: A total of 576 subjects were initially enrolled in the study. Of these, one subject was older than protocol defined age range for the first vaccination, and therefore did not receive any vaccination.

Baseline characteristics

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Reporting group title

10PP-LD/Infanrix hexa Group

Reporting group description

Reporting group title

10PP-HD/Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix/Infanrix hexa Group

Reporting group description

Reporting group title

Prevnar 13/Infanrix hexa Group

Reporting group description

Reporting group values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group	Total
Number of subjects	146	142	145	142	575
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	10.3 ( 2.49 )	10.1 ( 2.7 )	10.1 ( 2.61 )	10.2 ( 2.64 )	-
Gender categorical
Units: Subjects
Female	65	67	70	66	268
Male	81	75	75	76	307

End points

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Reporting group title

10PP-LD/Infanrix hexa Group

Reporting group description

Reporting group title

10PP-HD/Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix/Infanrix hexa Group

Reporting group description

Reporting group title

Prevnar 13/Infanrix hexa Group

Reporting group description

Primary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms related to vaccination – Primary Phase of the study.

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End point title

Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms related to vaccination – Primary Phase of the study. ^[1]

End point description

Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than or equal to [>=] 38 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 (G3) Drowsiness = Drowsiness that prevented normal activity. G3 Irritability = Crying that could not be comforted/prevented normal activity. G3 Loss of appetite = Subject did not eat at all. G3 Fever = Rectal temperature higher than (>) 40.0°C. Primary results correspond to results for occurrences of G3 fever symptoms assessed by the investigators as related to vaccination (Related G3 fever).

End point type

Primary

End point timeframe

Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course

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

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	146	142	144	142
Units: Subject
Any Drowsiness, post D1 (N=146;142;144;142)	82	76	72	77
G3 Drowsiness, post D1 (N=146;142;144;142)	4	0	2	2
Related Drowsiness, post D1 (N=146;142;144;142)	63	58	52	58
Any Irritability, post D1 (N=146;142;144;142)	93	82	89	82
G3 Irritability, post D1 (N=146;142;144;142)	6	9	9	5
Related Irritability, post D1 (N=146;142;144;142)	70	62	66	57
Any Loss Appet., post D1 (N=146;142;144;142)	38	32	39	32
G3 Loss Appet., post D1 (N=146;142;144;142)	0	1	0	0
Related Loss Appet., post D1 (N=146;142;144;142)	28	26	29	21
Any Fever, post D1 (N=146;142;144;142)	45	32	53	28
G3 Fever, post D1 (N=146;142;144;142)	0	0	0	0
Related Fever, post D1 (N=146;142;144;142)	33	25	44	27
Related G3 Fever, post D1 (N=146;142;144;142)	0	0	0	0
Any Drowsiness, post D2 (N=146;142;144;142)	71	63	70	66
G3 Drowsiness, post D2 (N=146;142;144;142)	4	2	1	1
Related Drowsiness, post D2 (N=146;142;144;142)	53	49	56	55
Any Irritability, post D2 (N=146;142;144;142)	88	81	86	87
G3 Irritability, post D2 (N=146;142;144;142)	8	3	5	6
Related Irritability, post D2 (N=146;142;144;142)	69	66	66	67
Any Loss Appet., post D2 (N=146;142;144;142)	32	30	28	30
G3 Loss Appet., post D2 (N=146;142;144;142)	1	2	0	0
Related Loss Appet., post D2 (N=146;142;144;142)	23	21	18	25
Any Fever, post D2 (N=146;142;144;142)	40	50	38	38
G3 Fever, post D2 (N=146;142;144;142)	0	0	0	0
Related Fever, post D2 (N=146;142;144;142)	32	39	33	31
Related G3 Fever, post D2 (N=146;142;144;142)	0	0	0	0
Any Drowsiness, post D3 (N=146;141;143;142)	57	48	56	48
Grade 3 Drowsiness, post D3 (N=146;141;143;142)	2	0	1	1
Related Drowsiness, post D3 (N=146;141;143;142)	51	38	44	36
Any Irritability, post D3 (N=146;141;143;142)	62	73	62	72
G3 Irritability, post D3 (N=146;141;143;142)	7	1	3	2
Related Irritability, post D3 (N=146;141;143;142)	52	55	48	53
Any Loss Appet., post D3 (N=146,141,143,142)	28	25	24	21
G3 Loss Appet., post D3 (N=146,141,143,142)	0	0	2	2
Related Loss Appet., post D3 (N=146,141,143,142)	22	20	18	13
Any Fever, post D3 (N=146;141;143;142)	28	23	27	30
G3 Fever, post D3 (N=146;141;143;142)	0	0	0	0
Related Fever, post D3 (N=146;141;143;142)	23	19	20	22
Related G3 Fever, post D3 (N=146;141;143;142)	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of subjects reporting fever > 40.0°C with causal relationship to vaccination after each primary vaccination dose and across doses in 10PP-LD/Infanrix hexa group and in Synflorix/Infanrix hexa group.

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End point title

Percentage of subjects reporting fever > 40.0°C with causal relationship to vaccination after each primary vaccination dose and across doses in 10PP-LD/Infanrix hexa group and in Synflorix/Infanrix hexa group. ^[2]

End point description

Grade 3 fever was defined as fever by rectal measurement >40.0°C. Related was defined a causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-LD/Infanrix hexa (or 10PP-LD) and Synflorix/Infanrix hexa (or 10PN) groups only.

End point type

Primary

End point timeframe

During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the difference between 2 groups: the 10PP-LD/Infanrix hexa group and the Synflorix/Infanrix hexa group.

End point values	10PP-LD/Infanrix hexa Group	Synflorix/Infanrix hexa Group
Number of subjects analysed	146	144
Units: percentage
number (not applicable)
Fever > 40.0°C & Related Dose 1 (N=146, 144)	0	0
Fever> 40.0°C & Related Dose 2 (N=146, 144)	0	0
Fever> 40.0°C & Related Dose 3 (N=146, 143)	0	0
Fever> 40.0°C & Related across doses (N=146,144)	0	0

Non-inferiority: 10PP-LD versus Synflorix - dose 1

Statistical analysis description

Non-inferiority of 10PP-LD vaccine vs Synflorix™ vaccine post dose 1 was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to dose 1 vaccination in the 10PP-LD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-LD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%.

Comparison groups

Synflorix/Infanrix hexa Group v 10PP-LD/Infanrix hexa Group

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[3]

Method

Kem Phillip's statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

2.57

Notes
[3] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % subjects with fever > 40.0°C and causal relationship to vaccination > the boundary expressed as 5% + 0.5*rate in the 10PN group.

Non-inferiority: 10PP-LD versus Synflorix - dose 2

Statistical analysis description

Non-inferiority of 10PP-LD vaccine vs Synflorix™ vaccine post dose 2 was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to dose 2 vaccination in the 10PP-LD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-LD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%

Comparison groups

Synflorix/Infanrix hexa Group v 10PP-LD/Infanrix hexa Group

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[4]

Method

Kem Phillip's statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

2.57

Notes
[4] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % subjects with fever > 40.0°C and causal relationship to vaccination > the boundary expressed as 5% + 0.5*rate in the 10PN group.

Non-inferiority: 10PP-LD versus Synflorix - dose 3

Statistical analysis description

Non-inferiority of 10PP-LD vaccine vs Synflorix™ vaccine post dose 3 was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to dose 3 vaccination in the 10PP-LD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-LD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%

Comparison groups

Synflorix/Infanrix hexa Group v 10PP-LD/Infanrix hexa Group

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[5]

Method

Kem Phillip's statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.62

upper limit

2.57

Notes
[5] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % subjects with fever > 40.0°C and causal relationship to vaccination > the boundary expressed as 5% + 0.5*rate in the 10PN group.

Non-inferiority:10PP-LD vs Synflorix -across doses

Statistical analysis description

Non-inferiority of 10PP-LD vaccine vs Synflorix™ vaccine across doses was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to vaccination, across doses, in the 10PP-LD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-LD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%

Comparison groups

Synflorix/Infanrix hexa Group v 10PP-LD/Infanrix hexa Group

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[6]

Method

Kem Phillip's statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

2.57

Notes
[6] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % subjects with fever > 40.0°C and causal relationship to vaccination > the boundary expressed as 5% + 0.5*rate in the 10PN group.

Primary: Percentage of subjects reporting fever > 40° C with causal relationship to vaccination after each primary vaccination dose and across doses in the 10PP-HD/Infanrix hexa group and in the Synflorix/Infanrix hexa group.

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End point title

Percentage of subjects reporting fever > 40° C with causal relationship to vaccination after each primary vaccination dose and across doses in the 10PP-HD/Infanrix hexa group and in the Synflorix/Infanrix hexa group. ^[7]

End point description

Grade 3 fever was defined as fever by rectal measurement >40.0°C. Related was defined a causal relationship to vaccination. This endpoint was assessed after each primary vaccination dose and across doses and in subjects in the 10PP-HD/Infanrix hexa (or 10PP-HD) and Synflorix/Infanrix hexa (or 10PN) groups only.

End point type

Primary

End point timeframe

During the 7-day (Days 0-6) post-vaccination period following each primary vaccination dose and across doses

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is related to the difference between 2 groups: the 10PP-HD/Infanrix hexa group and the Synflorix/Infanrix hexa group.

End point values	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group
Number of subjects analysed	142	144
Units: percentage
number (not applicable)
Fever > 40.0°C & Related Dose 1 (N= 142,144)	0	0
Fever> 40.0°C & Related Dose 2 (N=142,144)	0	0
Fever> 40.0°C & Related Dose 3 (N=141,143)	0	0
Fever> 40.0°C & Related across doses (N=142,144)	0	0

Non-inferiority: 10PP-HD versus Synflorix- dose 1

Statistical analysis description

Non-inferiority of 10PP-HD vaccine vs Synflorix™ vaccine post dose 1 was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to dose 1 vaccination in the 10PP-HD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-HD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%.

Comparison groups

10PP-HD/Infanrix hexa Group v Synflorix/Infanrix hexa Group

Number of subjects included in analysis

286

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[8]

Method

Kem Philips' statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

2.64

Notes
[8] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % of subjects with fever > 40.0°C and causal relationship to vaccination above the boundary expressed as 5% + 0.5*rate in the 10PN group.

Non-inferiority: 10PP-HD versus Synflorix- dose 2

Statistical analysis description

Non-inferiority of 10PP-HD vaccine vs Synflorix™ vaccine post dose 2 was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to dose 2 vaccination in the 10PP-HD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-HD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%.

Comparison groups

10PP-HD/Infanrix hexa Group v Synflorix/Infanrix hexa Group

Number of subjects included in analysis

286

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[9]

Method

Kem Philips' statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

2.64

Notes
[9] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % of subjects with fever > 40.0°C and causal relationship to vaccination above the boundary expressed as 5% + 0.5*rate in the 10PN group.

Non-inferiority: 10PP-HD versus Synflorix - dose 3

Statistical analysis description

Non-inferiority of 10PP-HD vaccine vs Synflorix™ vaccine post dose 3 was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to dose 3 vaccination in the 10PP-HD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-HD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%.

Comparison groups

10PP-HD/Infanrix hexa Group v Synflorix/Infanrix hexa Group

Number of subjects included in analysis

286

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[10]

Method

Kem Philips' statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.63

upper limit

2.66

Notes
[10] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % of subjects with fever > 40.0°C and causal relationship to vaccination above the boundary expressed as 5% + 0.5*rate in the 10PN group.

Non-inferiority: 10PP-HD vs Synflorix-across doses

Statistical analysis description

Non-inferiority of 10PP-HD vaccine vs Synflorix™ vaccine across doses was assessed by computing the difference in percentages of subjects reporting Grade 3 fever causally related to vaccination, across doses, in the 10PP-HD Group minus 10PN Group. Non-inferiority was supported if one could rule out an increase in terms of percentage of subjects (10PP-HD Group minus 10PN Group) above 5% + half the incidence in the 10PN Group (= null hypothesis) as shown by a 1-sided P-value < 5%.

Comparison groups

10PP-HD/Infanrix hexa Group v Synflorix/Infanrix hexa Group

Number of subjects included in analysis

286

Analysis specification

Pre-specified

Analysis type

non-inferiority

P-value

= 0.003 ^[11]

Method

Kem Philips' statistical test

Parameter type

Difference in percentage

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.61

upper limit

2.64

Notes
[11] - 1-sided P-value computed using Kem Philips'approach for ruling out an increase in % of subjects with fever > 40.0°C and causal relationship to vaccination above the boundary expressed as 5% + 0.5*rate in the 10PN group.

Secondary: Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Primary Phase of the study.

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End point title

Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Primary Phase of the study.

End point description

Antibody concentrations against dPly and PhtD (anti-dPly and anti-PhtD, respectively) were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). Cut-offs for seropositivity were concentrations higher than or equal to (≥)12 EL.U/mL for anti-dPly antibodies and ≥ 17 EL.U/mL for anti-PhtD antibodies. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	130	134	136	131
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-dPly – At Month 3	9408.42 (8182.15 to 10818.47)	12137.96 (10641.83 to 13844.44)	459.97 (398.31 to 531.18)	472.88 (404.48 to 552.86)
Anti-PhtD – At Month 3	1456.57 (1250.65 to 1696.39)	1996.61 (1734.17 to 2298.75)	523.61 (453.71 to 604.28)	552.01 (469.55 to 648.95)

No statistical analyses for this end point

Secondary: Antibody concentrations against protein D (anti-PD) – Primary Phase of the study.

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End point title

Antibody concentrations against protein D (anti-PD) – Primary Phase of the study.

End point description

Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in ELISA Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was a concentration of anti-PD antibodies ≥ 100 EL.U/mL. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	132	134	137	132
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD – At Month 3	1135.7 (927.8 to 1390.1)	1323.3 (1099.7 to 1592.4)	1539 (1258.4 to 1882.1)	147 (112.3 to 192.3)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes – Primary Phase of the study.

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End point title

Antibody concentrations against pneumococcal serotypes – Primary Phase of the study.

End point description

Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	132	135	137	132
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-1 At Month 3 (N=131,131,134,132)	1.57 (1.36 to 1.8)	1.58 (1.36 to 1.83)	1.49 (1.28 to 1.74)	2.2 (1.86 to 2.6)
ANTI-4 At Month 3 (N=131,133,133,132)	2.04 (1.74 to 2.39)	2.11 (1.83 to 2.43)	1.82 (1.55 to 2.14)	2.43 (2.05 to 2.88)
ANTI-5 At Month 3 (N=132,134,134,132)	2.46 (2.13 to 2.85)	2.55 (2.22 to 2.92)	2.31 (2 to 2.67)	2.77 (2.27 to 3.38)
ANTI-6B At Month 3 (N=130,129,133,132)	0.36 (0.29 to 0.46)	0.37 (0.31 to 0.45)	0.4 (0.32 to 0.51)	0.46 (0.37 to 0.57)
ANTI-7F At Month 3 (N=130,131,134,132)	2.12 (1.86 to 2.41)	2.21 (1.97 to 2.48)	2.2 (1.92 to 2.5)	2.94 (2.51 to 3.46)
ANTI-9V At Month 3 (N=132,135,137,132)	1.83 (1.59 to 2.12)	1.95 (1.73 to 2.2)	1.99 (1.72 to 2.3)	2.33 (1.96 to 2.76)
ANTI-14 At Month 3 (N=132,133,135,132)	3.57 (3.08 to 4.14)	3.72 (3.3 to 4.18)	3.91 (3.41 to 4.48)	4.18 (3.41 to 5.13)
ANTI-18C At Month 3 (N=132,132,135,132)	2.27 (1.93 to 2.67)	2.18 (1.84 to 2.59)	2.45 (2.04 to 2.95)	2.56 (2.14 to 3.07)
ANTI-19F At Month 3 (N=132,132,135,132)	4.29 (3.63 to 5.07)	4.13 (3.52 to 4.85)	4.51 (3.79 to 5.36)	3.5 (2.94 to 4.18)
ANTI-23F At Month 3 (N=131,133,135,132)	0.67 (0.54 to 0.82)	0.62 (0.5 to 0.78)	0.67 (0.54 to 0.82)	1.48 (1.17 to 1.88)
ANTI-3 At Month 3 (N=130,129,132,132)	0.05 (0.04 to 0.06)	0.06 (0.05 to 0.07)	0.05 (0.05 to 0.06)	2.47 (2.08 to 2.93)
ANTI-6A At Month 3 (N=129,132,133,132)	0.13 (0.1 to 0.16)	0.11 (0.09 to 0.14)	0.11 (0.09 to 0.14)	2.05 (1.69 to 2.5)
ANTI-19A At Month 3 (N=130,129,134,132)	0.18 (0.14 to 0.23)	0.17 (0.13 to 0.21)	0.16 (0.13 to 0.2)	2.77 (2.34 to 3.28)

No statistical analyses for this end point

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

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End point title

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

End point description

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

End point type

Secondary

End point timeframe

Within the 7-day (Days 0-6) periods post vaccination, after each dose (D) of the 3-dose primary vaccination course

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	146	142	144	142
Units: Subject
Any Pain, post D1 (N=146;142;144;142)	52	46	53	40
Grade 3 Pain, post D1 (N=146;142;144;142)	0	2	3	0
Any Redness, post D1 (N=146;142;144;142)	59	58	52	51
Grade 3 Redness, post D1 (N=146;142;144;142)	0	0	3	2
Any Swelling, post D1 (N=146;142;144;142)	47	46	34	37
Grade 3 Swelling, post D1 (N=146;142;144;142)	3	5	3	6
Any Pain, post D2 (N=146;142;144;142)	52	49	42	43
Grade 3 Pain, post D2 (N=146;142;144;142)	2	0	1	2
Any Redness, post D2 (N=146;142;144;142)	67	67	63	59
Grade 3 Redness, post D2 (N=146;142;144;142)	2	2	3	0
Any Swelling, post D2 (N=146;142;144;142)	49	56	43	38
Grade 3 Swelling, post D2 (N=146;142;144;142)	5	4	2	3
Any Pain, post D3 (N=146;141;143;142)	41	35	37	45
Grade 3 Pain, post D3 (N=146;141;143;142)	2	3	1	1
Any Redness, post D3 (N=146;141;143;142)	65	65	58	65
Grade 3 Redness, post D3 (N=146;141;143;142)	3	2	0	3
Any Swelling, post D3 (N=146;141;143;142)	52	52	43	43
Grade 3 Swelling, post D3 (N=146;141;143;142)	6	3	3	5

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Within the 7-day (Days 0-6) period after booster vaccination

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	144	140	139	140
Units: Subject
Any Pain, (N=144;140;139;140)	77	73	61	68
Grade 3 Pain (N=144;140;139;140)	7	6	3	4
Any Redness (N=144;140;139;140)	83	81	68	66
Grade 3 Redness (N=144;140;139;140)	11	15	12	7
Any Swelling (N=144;140;139;140)	70	55	49	59
Grade 3 Swelling (N=144;140;139;140)	8	8	7	10

No statistical analyses for this end point

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

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End point title

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

End point description

Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than [≥] 38 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity and relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigator as causally related to vaccination. Grade 3 (G3) Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irritability = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Axillary temperature higher than (>) 40.0°C.

End point type

Secondary

End point timeframe

Within the 7-day (Days 0-6) period post vaccination after booster vaccination

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	144	140	139	140
Units: Subject
Any Drowsiness (N=144;140;139;140)	77	64	66	73
G3 Drowsiness (N=144;140;139;140)	1	5	1	1
Related Drowsiness (N=144;140;139;140)	68	61	59	69
Any Irritability (N=144;140;139;140)	95	84	82	90
G3 Irritability (N=144;140;139;140)	12	8	4	8
Related Irritability (N=144;140;139;140)	86	82	76	83
Any Loss Appet. (N=144;140;139;140)	49	38	36	57
G3 Loss Appet. (N=144;140;139;140)	3	4	2	2
Related Loss Appet. (N=144;140;139;140)	42	38	33	49
Any Fever (N=144;140;139;140)	50	55	51	53
G3 Fever (N=144;140;139;140)	1	0	1	3
Related Fever (N=144;140;139;140)	44	52	45	47

No statistical analyses for this end point

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

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End point title

Number of subjects with unsolicited adverse events (AEs) – Primary Phase of the study.

End point description

An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination.

End point type

Secondary

End point timeframe

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

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	146	142	145	142
Units: Subject
Any AE	55	68	64	61

No statistical analyses for this end point

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

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End point title

Number of subjects with unsolicited adverse events (AEs) – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

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

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	144	140	140	140
Units: Subject
Any AE	40	26	27	34

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Booster Phase of the study.

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End point title

Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	130	129	129	129
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-dPly – Month 10 (N=130,128,129,129)	6674.42 (5628.57 to 7914.6)	5592.85 (4750.83 to 6584.1)	495.02 (393.19 to 623.22)	737.71 (587.67 to 926.06)
Anti-dPly – Month 11 (N=129,129,129,125)	24720.4 (21863.04 to 27951.19)	29838.18 (26892.53 to 33106.48)	582.85 (463.4 to 733.09)	791.42 (628.23 to 997)
Anti-PhtD – Month 10 (N=130,128,129,129)	910.8 (718.85 to 1154)	829.12 (671.12 to 1024.32)	209.27 (153.16 to 285.95)	381.66 (274.64 to 530.39)
Anti-PhtD – Month 11 (N=129,129,129,125)	3528.25 (2952.68 to 4216.01)	3777.39 (3181.74 to 4484.55)	266.58 (190.06 to 373.91)	469.16 (335.29 to 656.46)

No statistical analyses for this end point

Secondary: Antibody concentrations against protein D (anti-PD) – Booster Phase of the study.

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End point title

Antibody concentrations against protein D (anti-PD) – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	131	130	131	129
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD – Month 10 (N=131,130,131,129)	434.3 (365.5 to 516)	472.8 (403.1 to 554.5)	698.2 (593.7 to 821)	81 (69.8 to 93.9)
Anti-PD – Month 11 (N=128,130,131,127)	1655.4 (1398.2 to 1960)	1631 (1404.5 to 1894.2)	2394.2 (2045.7 to 2802.1)	85.7 (73.6 to 99.8)

No statistical analyses for this end point

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

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End point title

Antibody concentrations against pneumococcal serotypes – Booster Phase of the study.

End point description

Antibodies assessed for this outcome measure were those against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (ANTI-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.05 µg/mL. This outcome concerns results for the Booster Phase of the study.

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	130	131	131	129
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-1 Month 10 (N=126,124,130,129)	0.3 (0.25 to 0.35)	0.3 (0.26 to 0.36)	0.26 (0.22 to 0.31)	0.49 (0.43 to 0.55)
ANTI-1 Month 11 (N=130,131,131,127)	2.62 (2.27 to 3.04)	2.61 (2.27 to 3)	2.41 (2.06 to 2.82)	3.78 (3.34 to 4.28)
ANTI-4 Month 10 (N=125,121,126,128)	0.5 (0.43 to 0.58)	0.51 (0.43 to 0.61)	0.58 (0.49 to 0.7)	0.4 (0.35 to 0.46)
ANTI-4 Month 11 (N=130,129,131,127)	4.1 (3.54 to 4.74)	3.9 (3.35 to 4.53)	3.98 (3.51 to 4.52)	4.36 (3.77 to 5.05)
ANTI-5 Month 10 (N=128,123,128,129)	0.59 (0.5 to 0.69)	0.58 (0.49 to 0.68)	0.55 (0.47 to 0.65)	0.85 (0.74 to 0.99)
ANTI-5 Month 11 (N=129,129,131,127)	3.48 (2.98 to 4.05)	3.44 (2.98 to 3.96)	3.33 (2.87 to 3.87)	7.52 (6.52 to 8.68)
ANTI-6B Month 10 (N=126,125,126,129)	0.45 (0.38 to 0.53)	0.47 (0.39 to 0.56)	0.46 (0.38 to 0.55)	0.25 (0.21 to 0.31)
ANTI-6B Month 11 (N=129,129,131,127)	2.04 (1.77 to 2.36)	1.96 (1.67 to 2.3)	2.28 (1.94 to 2.68)	3.11 (2.65 to 3.64)
ANTI-7F Month 10 (N=127,126,127,129)	0.94 (0.82 to 1.09)	1 (0.88 to 1.15)	0.98 (0.85 to 1.13)	1.34 (1.18 to 1.53)
ANTI-7F Month 11 (N=129,129,131,127)	4.72 (4.13 to 5.4)	4.7 (4.19 to 5.27)	4.87 (4.32 to 5.5)	7.68 (6.84 to 8.61)
ANTI-9V Month 10 (N=127,126,128,128)	0.77 (0.65 to 0.9)	0.97 (0.84 to 1.12)	0.99 (0.85 to 1.16)	0.58 (0.5 to 0.68)
ANTI-9V Month 11 (N=129,129,131,127)	4.48 (3.9 to 5.14)	4.91 (4.32 to 5.58)	5.2 (4.52 to 5.97)	6.57 (5.67 to 7.6)
ANTI-14 Month 10 (N=129,126,128,129)	1.36 (1.12 to 1.65)	1.43 (1.18 to 1.73)	1.57 (1.28 to 1.93)	2.06 (1.72 to 2.47)
ANTI-14 Month 11 (N=129,129,131,127)	6.06 (5.18 to 7.09)	7.18 (6.14 to 8.39)	6.63 (5.59 to 7.86)	11.43 (9.81 to 13.3)
ANTI-18C Month 10 (N=126,124,126,129)	0.75 (0.64 to 0.87)	0.76 (0.65 to 0.89)	0.92 (0.77 to 1.1)	0.75 (0.65 to 0.85)
ANTI-18C Month 11 (N=129,129,131,127)	6.68 (5.76 to 7.75)	6.38 (5.48 to 7.42)	7.65 (6.76 to 8.67)	6.4 (5.5 to 7.45)
ANTI-19F Month 10 (N=127,126,127,128)	1.25 (1.05 to 1.47)	1.13 (0.96 to 1.33)	1.3 (1.06 to 1.58)	0.66 (0.53 to 0.82)
ANTI-19F Month 11 (N=130,129,131,127)	6.73 (5.77 to 7.83)	7.22 (6.25 to 8.33)	7.84 (6.78 to 9.06)	7.43 (6.35 to 8.69)
ANTI-23F Month 10 (N=126,123,125,128)	0.46 (0.38 to 0.56)	0.47 (0.38 to 0.58)	0.57 (0.48 to 0.68)	0.37 (0.3 to 0.44)
ANTI-23F Month 11 (N=129,129,131,127)	3.2 (2.68 to 3.83)	3.2 (2.7 to 3.78)	3.72 (3.21 to 4.31)	7.1 (6.05 to 8.35)
ANTI-3 Month 10 (N=125,126,129,128)	0.05 (0.04 to 0.06)	0.05 (0.04 to 0.06)	0.05 (0.04 to 0.06)	0.32 (0.27 to 0.38)
ANTI-3 Month 11 (N=128,128,131,127)	0.06 (0.05 to 0.08)	0.05 (0.04 to 0.07)	0.06 (0.05 to 0.07)	1.83 (1.58 to 2.12)
ANTI-6A Month 10 (N=129,127,128,129)	0.19 (0.15 to 0.24)	0.18 (0.15 to 0.22)	0.2 (0.16 to 0.24)	0.7 (0.59 to 0.83)
ANTI-6A Month 11 (N=130,130,131,127)	0.89 (0.72 to 1.11)	0.74 (0.59 to 0.93)	0.99 (0.78 to 1.26)	7.77 (6.6 to 9.14)
ANTI-19A Month 10 (N=126,124,128,129)	0.18 (0.15 to 0.22)	0.15 (0.12 to 0.18)	0.18 (0.14 to 0.22)	0.57 (0.44 to 0.73)
ANTI-19A Month 11 (N=128,128,131,127)	1.12 (0.89 to 1.41)	1.03 (0.8 to 1.31)	1.23 (0.99 to 1.52)	7.77 (6.43 to 9.39)

No statistical analyses for this end point

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

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End point title

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

End point description

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The Seropositivity cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8, except for the OPA-19A for which the titer was ≥ to the serotype-specific Lower Limit of Quantification (=143). This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	63	57	66	63
Units: Titers
geometric mean (confidence interval 95%)
OPA-1 At Month 3 (N=63,57,65,62)	38.6 (24.6 to 60.5)	27.8 (17.5 to 44.2)	29.4 (19.4 to 44.5)	68.9 (47.5 to 99.9)
OPA-4 At Month 3 (N=60,57,66,63)	703.7 (533.5 to 928.2)	844.4 (660.8 to 1079)	819.2 (652.7 to 1028.1)	748.1 (509.9 to 1097.5)
OPA-5 At Month 3 (N=63,56,65,63)	47.3 (33.6 to 66.6)	60.6 (44.1 to 83.3)	50.3 (37.2 to 68.1)	72.9 (52.2 to 101.8)
OPA-6B At Month 3 (N=61,57,63,63)	399.6 (249.4 to 640.4)	454.7 (299.8 to 689.7)	409.7 (251 to 668.7)	884.9 (569.3 to 1375.5)
OPA-7F At Month 3 (N=61,55,64,62)	3212.6 (2434.8 to 4238.8)	3697.6 (2748.6 to 4974.1)	4234.2 (3203 to 5597.4)	7394.5 (4411.1 to 12395.7)
OPA-9V At Month 3 (N=60,56,64,62)	1942.4 (1381.9 to 2730.1)	1520.7 (1109.4 to 2084.5)	1983.6 (1507.2 to 2610.7)	2242.8 (1474.7 to 3411.1)
OPA-14 At Month 3 (N=59,56,62,61)	1405.3 (1060.3 to 1862.4)	1334.9 (1013.9 to 1757.4)	1575.3 (1143.5 to 2170.1)	2410.6 (1516.6 to 3831.5)
OPA-18C At Month 3 (N=58,52,59,58)	108.1 (72.6 to 161.2)	102.7 (70.3 to 150)	169.4 (121.9 to 235.4)	257.6 (179.4 to 369.9)
OPA-19F At Month 3 (N=61,56,64,63)	211.6 (139.6 to 320.7)	344.1 (240.6 to 492)	381.6 (256.8 to 566.9)	142.5 (98.9 to 205.4)
OPA-23F At Month 3 (N=60,54,63,63)	1275.6 (771.1 to 2110.3)	2170.3 (1559.9 to 3019.6)	1757.9 (1191.4 to 2593.7)	4437.1 (2874.9 to 6848.2)
OPA-3 At Month 3 (N=55,51,58,61)	5 (3.9 to 6.4)	4.5 (3.9 to 5.2)	4.6 (4 to 5.3)	88.4 (67.3 to 116)
OPA-6A At Month 3 (N=63,56,64,62)	43.2 (23.8 to 78.5)	59.6 (35.4 to 100.3)	44.7 (26.2 to 76.2)	1726 (1113.9 to 2674.4)
OPA-19A At Month 3 (N=33,34,36,49)	576.0 (340.6 to 974.3)	914.6 (586.8 to 1425.6)	905.2 (628.2 to 1304.5)	2915.3 (2270.3 to 3743.6)

No statistical analyses for this end point

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

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End point title

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

End point description

Titers for opsonophagocytic activity assessed for this outcome measure were those for opsonophagocytic activity against the vaccine/cross-reactive pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F (OPA-1, -3, -4, -5, -6A, -6B, -7F, -9V, -14, -18C, -19A, -19F and -23F). The seropositivity cut-off of the assay was a titer for opsonophagocytic activity higher than or equal to (≥) 8, except for the OPA-19A for which the titer was ≥ to the serotype-specific Lower Limit of Quantification (=143). This outcome concerns results for the Booster Phase of the study.

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	68	58	68	62
Units: Titers
geometric mean (confidence interval 95%)
OPA-1 Month 10 (N=44,40,45,43)	12.4 (7.6 to 20.1)	13.2 (8.3 to 21.1)	18.7 (11.2 to 31.4)	10.3 (6.8 to 15.5)
OPA-1 Month 11 (N=68,56,66,59)	373.5 (253.3 to 550.8)	369.2 (252.8 to 539.4)	300 (213.2 to 422.1)	369.3 (281.4 to 484.6)
OPA-4 Month 10 (N=41,36,42,34)	36.2 (19.1 to 68.4)	48.3 (25.6 to 91)	122.3 (75 to 199.6)	18.5 (9.7 to 35.4)
OPA-4 Month 11 (N=68,57,68,62)	1370.7 (1034.2 to 1816.6)	1634.8 (1284.8 to 2080.3)	2043.3 (1609.1 to 2594.6)	2882.6 (2252.4 to 3689.1)
OPA-5 Month 10 (N=44,36,45,42)	9.3 (6.9 to 12.5)	10.5 (6.9 to 16.1)	9.5 (6.9 to 12.9)	8.7 (6.3 to 12)
OPA-5 Month 11 (N=68,56,66,61)	154.5 (111.8 to 213.4)	166.8 (118.4 to 234.8)	139.3 (102.3 to 189.8)	327.4 (254.2 to 421.8)
OPA-6B Month 10 (N=36,36,40,36)	103.2 (56.5 to 188.4)	174.5 (102.1 to 298.2)	136.9 (76.1 to 246.4)	113.8 (59.3 to 218.6)
OPA-6B Month 11 (N=66,58,68,62)	802.1 (531.7 to 1210)	700.3 (481.3 to 1018.8)	1013.8 (744.6 to 1380.3)	2731.1 (1972.7 to 3781.1)
OPA-7F Month 10 (N=42,38,46,40)	795.5 (560.1 to 1129.9)	886.4 (599.1 to 1311.5)	1322.5 (961.5 to 1819.1)	1895.8 (1420.6 to 2530)
OPA-7F Month 11 (N=68,55,64,61)	5819.9 (4473.1 to 7572.2)	5733.8 (4165 to 7893.5)	8336.9 (6357.9 to 10931.8)	18012.3 (13872.4 to 23387.7)
OPA-9V Month 10 (N=39,37,40,38)	281.5 (175.4 to 451.7)	340.8 (224 to 518.5)	433.7 (318.3 to 591)	510.4 (344.6 to 755.8)
OPA-9V Month 11 (N=68,56,67,61)	2001.6 (1506.6 to 2659.3)	2436.5 (1734.5 to 3422.6)	3711.7 (2881.2 to 4781.4)	6839.2 (5464.7 to 8559.3)
OPA-14 Month 10 (N=35,34,40,32)	275.8 (175.2 to 434.3)	208.1 (111.9 to 386.9)	355.6 (216.3 to 584.8)	483 (286.9 to 813.1)
OPA-14 Month 11 (N=68,55,68,61)	2216.9 (1678 to 2928.9)	2297.4 (1640 to 3218.4)	2488.9 (1942.5 to 3189)	3545 (2465.2 to 5097.8)
OPA-18C Month 10 (N=36,35,35,28)	5.1 (4 to 6.6)	6.3 (4.6 to 8.7)	6.7 (4.9 to 9)	4.8 (3.9 to 6.1)
OPA-18C Month 11 (N=68,55,62,60)	374.6 (271.2 to 517.4)	303.6 (197.7 to 466.3)	511 (356.7 to 732.2)	464.4 (327.7 to 658.1)
OPA-19F Month 10 (N=42,40,46,41)	18 (11.2 to 29)	31 (19.2 to 49.9)	30.7 (19.2 to 49.2)	7.4 (4.8 to 11.5)
OPA-19F Month 11 (N=67,56,66,61)	650.2 (444.1 to 951.9)	778.9 (500.4 to 1212.3)	1053.9 (812.6 to 1366.8)	767.1 (582.1 to 1010.9)
OPA-23F Month 10 (N=41,35,42,37)	189.6 (83.5 to 430.5)	281.4 (123.2 to 642.8)	242.5 (106.5 to 552.2)	367.4 (150.3 to 897.8)
OPA-23F Month 11 (N=68,56,66,60)	3621 (2534.5 to 5173.2)	2563.6 (1831.6 to 3588.2)	4465.4 (3368.6 to 5919.3)	32508 (23754.9 to 44486.3)
OPA-3 Month 10 (N=31,23,30,24)	6.7 (4.7 to 9.5)	8.3 (4.9 to 14)	6.3 (4.6 to 8.8)	12 (7.6 to 19.1)
OPA-3 Month 11 (N=64,48,65,60)	7.8 (5.7 to 10.6)	7.8 (5.4 to 11.2)	9.2 (6.8 to 12.5)	333.9 (260.3 to 428.3)
OPA-6A Month 10 (N=41,35,42,35)	26.5 (13.2 to 52.9)	23.3 (10.3 to 53.1)	18.7 (9.8 to 35.7)	129.7 (61.2 to 274.7)
OPA-6A Month 11 (N=64,57,67,61)	163.1 (94 to 283.1)	190 (106.6 to 338.4)	276.2 (174.8 to 436.6)	4855.3 (3606.3 to 6536.8)
OPA-19A Month 10 (N=38,30,34,46)	211.8 (139.2 to 322.4)	262.0 (157.8 to 435.1)	315.6 (193.5 to 514.6)	776.3 (542.2 to 1111.7)
OPA-19A Month 11 (N=47,42,53,47)	2006.3 (1539.1 to 2615.3)	2609.5 (1919.1 to 3548.2)	2699.1 (2262.2 to 3220.5)	7137.0 (5909.4 to 8619.6)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Primary Phase of the study.

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End point title

Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Primary Phase of the study.

End point description

Antibody concentrations were expressed as geometric mean concentrations (GMCs) in International Units per milliliter (IU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.1 IU/mL. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	59	54	57	60
Units: IU/mL
geometric mean (confidence interval 95%)
ANTI-D At Month 3	3.251 (2.729 to 3.873)	3.185 (2.556 to 3.968)	3.353 (2.756 to 4.08)	2.933 (2.464 to 3.492)
ANTI-T At Month 3	2.579 (2.187 to 3.041)	2.193 (1.819 to 2.643)	2.252 (1.93 to 2.627)	1.416 (1.166 to 1.719)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Booster Phase of the study.

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End point title

Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	45	50	46	49
Units: IU/mL
geometric mean (confidence interval 95%)
ANTI-D At Month 10 (N=43,50,42,49)	0.731 (0.575 to 0.929)	0.587 (0.461 to 0.747)	0.651 (0.507 to 0.836)	0.614 (0.497 to 0.758)
ANTI-D At Month 11 (N=45,47,46,48)	9.872 (8.191 to 11.898)	8.688 (7.026 to 10.743)	9.742 (7.991 to 11.878)	8.29 (6.943 to 9.899)
ANTI-T At Month 10 (N=43,50,42,49)	0.815 (0.665 to 0.999)	0.727 (0.57 to 0.927)	0.726 (0.604 to 0.874)	0.371 (0.28 to 0.493)
ANTI-T At Month 11 (N=45,47,46,48)	8.725 (7.259 to 10.488)	8.703 (7.415 to 10.215)	9.929 (8.653 to 11.394)	5.04 (4.074 to 6.234)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Primary Phase of the study.

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End point title

Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Primary Phase of the study.

End point description

Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs) in Elisa Units per milliliter (EL.U/mL). The seropositivity cut-off of the assay was an antibody concentration higher than or equal to (≥) 5 EL.U/mL. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	59	54	57	60
Units: EL.U/mL
geometric mean (confidence interval 95%)
ANTI-PT At Month 3 (N=59,54,57,59)	69 (59.9 to 79.4)	64.3 (54.8 to 75.3)	70 (61.6 to 79.4)	64.6 (53.2 to 78.3)
ANTI-FHA At Month 3 (N=59,54,57,60)	187.9 (159 to 222.1)	178.1 (150.2 to 211.2)	157.1 (132.5 to 186.3)	188.6 (156.4 to 227.5)
ANTI-PRN At Month 3 (N=59,54,57,60)	95.1 (79.2 to 114.4)	79.5 (63.6 to 99.2)	91.4 (75.2 to 111.1)	87.2 (70.6 to 107.5)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Booster Phase of the study.

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End point title

Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	45	50	46	49
Units: EL.U/mL
geometric mean (confidence interval 95%)
ANTI-PT At Month 10 (N=43,50,42,49)	17.5 (13.4 to 22.9)	12.7 (9.9 to 16.3)	12.1 (9.7 to 15.1)	12.2 (9.6 to 15.5)
ANTI-PT At Month 11 (N=45,47,46,48)	93.8 (75.4 to 116.6)	90.6 (73.5 to 111.7)	95.7 (80.1 to 114.3)	85.2 (70.3 to 103.2)
ANTI-FHA At Month 10 (N=43,50,42,49)	63 (50.3 to 78.9)	51.7 (40.1 to 66.6)	48.5 (38.3 to 61.5)	54.2 (42.5 to 69.2)
ANTI-FHA At Month 11 (N=45,47,46,48)	359.4 (291.3 to 443.5)	380.1 (311.9 to 463.2)	308.4 (252 to 377.3)	376.7 (322.6 to 439.8)
ANTI-PRN At Month 10 (N=43,50,42,49)	21.8 (15.8 to 30.1)	16.1 (11.7 to 22.2)	14.3 (10.7 to 19.3)	14.3 (10.6 to 19.3)
ANTI-PRN At Month 11 (N=45,47,46,48)	294.8 (227 to 382.8)	228.5 (174.2 to 299.7)	224.2 (180 to 279.1)	197.3 (154.3 to 252.2)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against hepatitis B (anti-HBs) – Primary Phase of the study.

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End point title

Concentrations of antibodies against hepatitis B (anti-HBs) – Primary Phase of the study.

End point description

Antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-International Units per milliliter (mIU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 10 mIU/mL. This outcome concerns results for the Primary Phase of the study. Note that the percentage of subjects with concentration ≥10 mIU/mL was overestimated due to the use of in-house assay overestimating concentrations between 10-100 mIU/mL. Accordingly, GMCs were also overestimated.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	50	43	47	48
Units: mIU/mL
geometric mean (confidence interval 95%)
ANTI-HBs At Month 3	676.7 (466.2 to 982.3)	619.1 (386.5 to 991.5)	719.8 (537 to 965)	877.4 (597 to 1289.4)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against hepatitis B (anti-HBs) – Booster Phase of the study.

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End point title

Concentrations of antibodies against hepatitis B (anti-HBs) – Booster Phase of the study.

End point description

Antibody concentrations were expressed as geometric mean concentrations (GMCs) in milli-International Units per milliliter (mIU/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 10 mIU/mL. This outcome concerns results for the Booster Phase of the study. * A decrease in the specificity of the anti-HB Enzyme-Linked ImmunoSorbent Assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete reanalysis. The retest has been performed in using Food and Drug Administration (FDA)-approved ChemiLuminescence ImmunoAssay (CLIA) commercial assay Centaur™.

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	60	65	62	64
Units: mIU/mL
geometric mean (confidence interval 95%)
ANTI-HBs At Month 10 (N=50,46,47,54)	299.2 (199 to 449.8)	287.1 (195.1 to 422.4)	166.6 (105.2 to 263.8)	174.5 (113.5 to 268.2)
ANTI-HBs At Month 11 (N=60,65,62,64)	4110.9 (2576.5 to 6558.9)	4234.8 (2961.4 to 6055.7)	3142.4 (2151.1 to 4590.6)	3116.4 (2142.5 to 4533)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Primary Phase of the study.

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End point title

Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Primary Phase of the study.

End point description

Antibody concentrations were expressed as geometric mean concentrations (GMCs) in microgram per milliliter (µg/mL). The seroprotection cut-off of the assay was an antibody concentration higher than or equal to (≥) 0.15 µg/mL or 1 µg/mL. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	59	54	57	60
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-PRP At Month 3	1.92 (1.433 to 2.573)	1.975 (1.39 to 2.806)	1.813 (1.33 to 2.472)	0.963 (0.69 to 1.344)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Booster Phase of the study.

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End point title

Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	45	50	46	49
Units: µg/mL
geometric mean (confidence interval 95%)
ANTI-PRP At Month 10 (N=43,50,42,49)	0.39 (0.279 to 0.546)	0.446 (0.306 to 0.651)	0.503 (0.36 to 0.703)	0.272 (0.193 to 0.384)
ANTI-PRP At Month 11 (N=45,47,46,48)	16.961 (11.652 to 24.689)	28.168 (20.58 to 38.554)	24.549 (16.379 to 36.795)	12.853 (8.301 to 19.899)

No statistical analyses for this end point

Secondary: Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Primary Phase of the study.

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End point title

Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Primary Phase of the study.

End point description

Antibody titers were measured by virus microneutralization test, expressed as geometric mean titers (GMTs). The cut-off of the assay for anti-1, anti-2 and anti-3 antibody was a titer higher than or equal to (≥) 8. This outcome concerns results for the Primary Phase of the study.

End point type

Secondary

End point timeframe

At Month 3, e. g. one month post-Dose 3 of pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	45	37	43	42
Units: Titers
geometric mean (confidence interval 95%)
ANTI-Polio 1 At Month 3 (N= 45,37,43,41)	175.7 (124.5 to 247.8)	138.2 (91 to 209.8)	190.3 (115.7 to 312.9)	173.7 (128.9 to 234)
ANTI-Polio 2 At Month 3 (N= 44,28,36,42)	134.3 (86.3 to 209.1)	114.7 (68.6 to 192)	177.6 (102.5 to 307.8)	148.4 (101.1 to 217.9)
ANTI-Polio 3 At Month 3 (N= 45,37,41,41)	445.7 (290.9 to 682.9)	432.2 (273 to 684.3)	552.7 (361.1 to 846.1)	538.6 (413.6 to 701.4)

No statistical analyses for this end point

Secondary: Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Booster Phase of the study.

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End point title

Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Booster Phase of the study.

End point description

End point type

Secondary

End point timeframe

At Months 10 and 11, e.g. prior to and at one month post booster vaccination with pneumococcal vaccine (10PP, Synflorix™ or Prevnar 13™)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	42	46	36	43
Units: Titers
geometric mean (confidence interval 95%)
ANTI-Polio 1 At Month 10 (N=35,37,32,41)	41.7 (25.9 to 67.3)	58.3 (35.6 to 95.6)	55.5 (33.9 to 90.9)	55.4 (38.3 to 80.1)
ANTI-Polio 1 At Month 11 (N=40,41,30,41)	1116 (696.1 to 1789.3)	1222 (737.1 to 2026.1)	1149.6 (764.3 to 1729)	1233.2 (898.9 to 1691.9)
ANTI-Polio 2 At Month 10 (N=39,46,36,43)	50.4 (33.4 to 76)	55.9 (35.6 to 87.8)	61 (40.2 to 92.7)	66.8 (48.6 to 91.9)
ANTI-Polio 2 At Month 11 (N=42,40,34,38)	1998.1 (1415 to 2821.5)	2332.2 (1739 to 3127.6)	2048.3 (1484.6 to 2825.9)	2284.8 (1705.1 to 3061.6)
ANTI-Polio 3 At Month 10 (N=36,40,33,38)	167.7 (113.3 to 248.3)	104.9 (68.7 to 160.2)	125.4 (81.2 to 193.6)	93.1 (66.2 to 130.9)
ANTI-Polio 3 At Month 11 (N=41,37,34,39)	2995.8 (2081.1 to 4312.6)	3626.3 (2623.6 to 5012.2)	2696.8 (1913.7 to 3800.4)	2820 (2127.9 to 3737.4)

No statistical analyses for this end point

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

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End point title

Number of subjects with serious adverse events (SAEs).

End point description

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

End point type

Secondary

End point timeframe

During the entire study period (Months 0-11)

End point values	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Number of subjects analysed	146	142	145	142
Units: Subject
Any SAE	13	9	21	17

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms: during the 7 days post-primary vaccination and post-booster vaccination. Unsolicited AEs during 31 days post-primary vaccination and post booster vaccination. SAEs: during the entire study period (Months 0-11).

Adverse event reporting additional description

Solicited symptoms results are presented only for subjects for whom results were available. Note: the occurences (all) numbers were not calculated during the analysis: data entered are equal to the subject affected numbers.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.1

Reporting group title

10PP-LD/Infanrix hexa Group

Reporting group description

Reporting group title

10PP-HD/Infanrix hexa Group

Reporting group description

Reporting group title

Synflorix/Infanrix hexa Group

Reporting group description

Reporting group title

Prevnar 13/Infanrix hexa Group

Reporting group description

Serious adverse events	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 146 (8.90%)	9 / 142 (6.34%)	21 / 145 (14.48%)	17 / 142 (11.97%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Concussion
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	3 / 145 (2.07%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	1 / 146 (0.68%)	1 / 142 (0.70%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Accidental exposure to product by child
subjects affected / exposed	1 / 146 (0.68%)	0 / 142 (0.00%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Phimosis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	2 / 142 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Burning sensation
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotonia
subjects affected / exposed	1 / 146 (0.68%)	0 / 142 (0.00%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotonic-hyporesponsive episode
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Localised oedema
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Aphthous ulcer
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal fissure
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Apnoea
subjects affected / exposed	1 / 146 (0.68%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Skin discolouration
subjects affected / exposed	1 / 146 (0.68%)	0 / 142 (0.00%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urticaria
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Psychomotor retardation
subjects affected / exposed	1 / 146 (0.68%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Breath holding
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 146 (0.68%)	1 / 142 (0.70%)	2 / 145 (1.38%)	3 / 142 (2.11%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
subjects affected / exposed	3 / 146 (2.05%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 146 (1.37%)	1 / 142 (0.70%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 146 (0.68%)	1 / 142 (0.70%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	1 / 146 (0.68%)	1 / 142 (0.70%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngitis
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	0 / 145 (0.00%)	2 / 142 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	1 / 146 (0.68%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 146 (0.68%)	1 / 142 (0.70%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Conjunctivitis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Exanthema subitum
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis Escherichia coli
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhinitis
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	0 / 145 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	0 / 146 (0.00%)	0 / 142 (0.00%)	1 / 145 (0.69%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	0 / 146 (0.00%)	1 / 142 (0.70%)	0 / 145 (0.00%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	10PP-LD/Infanrix hexa Group	10PP-HD/Infanrix hexa Group	Synflorix/Infanrix hexa Group	Prevnar 13/Infanrix hexa Group
Total subjects affected by non serious adverse events
subjects affected / exposed	141 / 146 (96.58%)	137 / 142 (96.48%)	139 / 145 (95.86%)	134 / 142 (94.37%)
General disorders and administration site conditions
Pain (primary vaccination)
Additional description: Symptom reported during the 7-day post-primary vaccination periods, across doses
subjects affected / exposed ^[1]	75 / 146 (51.37%)	73 / 142 (51.41%)	72 / 144 (50.00%)	64 / 142 (45.07%)
occurrences all number	75	73	72	64
Redness (primary vaccination)
Additional description: Symptom reported during the 7-day post-primary vaccination periods, across doses
subjects affected / exposed ^[2]	96 / 146 (65.75%)	97 / 142 (68.31%)	88 / 144 (61.11%)	83 / 142 (58.45%)
occurrences all number	96	97	88	83
Swelling (primary vaccination)
Additional description: Symptom reported during the 7-day post-primary vaccination periods, across doses
subjects affected / exposed ^[3]	82 / 146 (56.16%)	74 / 142 (52.11%)	60 / 144 (41.67%)	59 / 142 (41.55%)
occurrences all number	82	74	60	59
Drowsiness (primary vaccination)
Additional description: Symptom reported during the 7-day post-primary vaccination periods, across doses
subjects affected / exposed ^[4]	107 / 146 (73.29%)	96 / 142 (67.61%)	98 / 144 (68.06%)	102 / 142 (71.83%)
occurrences all number	107	96	98	102
Irritability (primary vaccination)
Additional description: Symptom reported during the 7-day post-primary vaccination periods, across doses
alternative assessment type: Non-systematic
subjects affected / exposed ^[5]	118 / 146 (80.82%)	113 / 142 (79.58%)	110 / 144 (76.39%)	113 / 142 (79.58%)
occurrences all number	118	113	110	113
Loss of appetite (primary vaccination)
Additional description: Symptom reported during the 7-day post-primary vaccination periods, across doses
subjects affected / exposed ^[6]	65 / 146 (44.52%)	59 / 142 (41.55%)	59 / 144 (40.97%)	57 / 142 (40.14%)
occurrences all number	65	59	59	57
Fever (primary vaccination)
Additional description: (rectal temperature >= 38°C) Symptom reported during the 7-day post-primary vaccination periods, across doses
subjects affected / exposed ^[7]	76 / 146 (52.05%)	71 / 142 (50.00%)	74 / 144 (51.39%)	65 / 142 (45.77%)
occurrences all number	76	71	74	65
Pain (booster vaccination)
Additional description: Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[8]	77 / 144 (53.47%)	73 / 140 (52.14%)	61 / 139 (43.88%)	68 / 140 (48.57%)
occurrences all number	77	73	61	68
Redness (booster vaccination)
Additional description: Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[9]	83 / 144 (57.64%)	81 / 140 (57.86%)	68 / 139 (48.92%)	66 / 140 (47.14%)
occurrences all number	83	81	68	66
Swelling (booster vaccination)
Additional description: Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[10]	70 / 144 (48.61%)	55 / 140 (39.29%)	49 / 139 (35.25%)	59 / 140 (42.14%)
occurrences all number	70	55	49	59
Drowsiness (booster vaccination)
Additional description: Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[11]	77 / 144 (53.47%)	64 / 140 (45.71%)	66 / 139 (47.48%)	73 / 140 (52.14%)
occurrences all number	77	64	66	73
Irritability (booster vaccination)
Additional description: Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[12]	95 / 144 (65.97%)	84 / 140 (60.00%)	82 / 139 (58.99%)	90 / 140 (64.29%)
occurrences all number	95	84	82	90
Loss of appetite (booster vaccination)
Additional description: Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[13]	49 / 144 (34.03%)	38 / 140 (27.14%)	36 / 139 (25.90%)	57 / 140 (40.71%)
occurrences all number	49	38	36	57
Fever (booster vaccination)
Additional description: (rectal temperature >= 38°C) Symptom reported during the 7-day post-booster vaccination period
subjects affected / exposed ^[14]	50 / 144 (34.72%)	55 / 140 (39.29%)	51 / 139 (36.69%)	53 / 140 (37.86%)
occurrences all number	50	55	51	53
Eye disorders
Conjunctivitis (primary vaccination)
Additional description: Unsolicited AE reported during the 31-day post-primary vaccination periods, across doses
alternative assessment type: Non-systematic
subjects affected / exposed	5 / 146 (3.42%)	9 / 142 (6.34%)	5 / 145 (3.45%)	3 / 142 (2.11%)
occurrences all number	5	9	5	3
Infections and infestations
Bronchitis (primary vaccination)
Additional description: Unsolicited AE reported during the 31-day post-primary vaccination periods, across doses
alternative assessment type: Non-systematic
subjects affected / exposed	6 / 146 (4.11%)	12 / 142 (8.45%)	11 / 145 (7.59%)	13 / 142 (9.15%)
occurrences all number	6	12	11	13
Nasopharyngitis (primary vaccination)
Additional description: Unsolicited AE reported during the 31-day post-primary vaccination periods, across doses
alternative assessment type: Non-systematic
subjects affected / exposed	10 / 146 (6.85%)	7 / 142 (4.93%)	12 / 145 (8.28%)	8 / 142 (5.63%)
occurrences all number	10	7	12	8
Nasopharyngitis (booster vaccination)
Additional description: Unsolicited AE reported during the 31-day post-booster vaccination period
alternative assessment type: Non-systematic
subjects affected / exposed ^[15]	9 / 144 (6.25%)	4 / 140 (2.86%)	3 / 140 (2.14%)	6 / 140 (4.29%)
occurrences all number	9	4	3	6
Rhinitis (primary vaccination)
Additional description: Unsolicited AE reported during the 31-day post-primary vaccination periods, across doses
alternative assessment type: Non-systematic
subjects affected / exposed	11 / 146 (7.53%)	11 / 142 (7.75%)	12 / 145 (8.28%)	14 / 142 (9.86%)
occurrences all number	11	11	12	14
Viral infection (primary vaccination)
Additional description: Unsolicited AE reported during the 31-day post-primary vaccination periods, across doses
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 146 (0.00%)	9 / 142 (6.34%)	5 / 145 (3.45%)	3 / 142 (2.11%)
occurrences all number	0	9	5	3

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

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Were there any global substantial amendments to the protocol? No

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.

The results of analysis of the anti-Ply haemolysis activity inhibition are not presented as assay was not validated.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms related to vaccination – Primary Phase of the study.

Primary: Number of subjects with any and Grade 3 solicited general symptoms and with solicited general symptoms related to vaccination – Primary Phase of the study.

Primary: Percentage of subjects reporting fever > 40.0°C with causal relationship to vaccination after each primary vaccination dose and across doses in 10PP-LD/Infanrix hexa group and in Synflorix/Infanrix hexa group.

Primary: Percentage of subjects reporting fever > 40.0°C with causal relationship to vaccination after each primary vaccination dose and across doses in 10PP-LD/Infanrix hexa group and in Synflorix/Infanrix hexa group.

Primary: Percentage of subjects reporting fever > 40° C with causal relationship to vaccination after each primary vaccination dose and across doses in the 10PP-HD/Infanrix hexa group and in the Synflorix/Infanrix hexa group.

Primary: Percentage of subjects reporting fever > 40° C with causal relationship to vaccination after each primary vaccination dose and across doses in the 10PP-HD/Infanrix hexa group and in the Synflorix/Infanrix hexa group.

Secondary: Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Primary Phase of the study.

Secondary: Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Primary Phase of the study.

Secondary: Antibody concentrations against protein D (anti-PD) – Primary Phase of the study.

Secondary: Antibody concentrations against protein D (anti-PD) – Primary Phase of the study.

Secondary: Antibody concentrations against pneumococcal serotypes – Primary Phase of the study.

Secondary: Antibody concentrations against pneumococcal serotypes – Primary Phase of the study.

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

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

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

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

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

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

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

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

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

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

Secondary: Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Booster Phase of the study.

Secondary: Antibody concentrations against pneumococcal pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD) proteins – Booster Phase of the study.

Secondary: Antibody concentrations against protein D (anti-PD) – Booster Phase of the study.

Secondary: Antibody concentrations against protein D (anti-PD) – Booster Phase of the study.

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

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

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

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

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

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

Secondary: Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Primary Phase of the study.

Secondary: Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Primary Phase of the study.

Secondary: Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Booster Phase of the study.

Secondary: Concentrations of antibodies against diphteria (anti-D) and tetanus (anti-T) – Booster Phase of the study.

Secondary: Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Primary Phase of the study.

Secondary: Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Primary Phase of the study.

Secondary: Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Booster Phase of the study.

Secondary: Concentrations of antibodies against pertussis toxoid (anti-PT), filamentous haemagglutinin (anti-FHA), pertactin (anti-PRN) – Booster Phase of the study.

Secondary: Concentrations of antibodies against hepatitis B (anti-HBs) – Primary Phase of the study.

Secondary: Concentrations of antibodies against hepatitis B (anti-HBs) – Primary Phase of the study.

Secondary: Concentrations of antibodies against hepatitis B (anti-HBs) – Booster Phase of the study.

Secondary: Concentrations of antibodies against hepatitis B (anti-HBs) – Booster Phase of the study.

Secondary: Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Primary Phase of the study.

Secondary: Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Primary Phase of the study.

Secondary: Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Booster Phase of the study.

Secondary: Concentrations of antibodies against polyribosyl ribitol phosphate (anti-PRP) – Booster Phase of the study.

Secondary: Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Primary Phase of the study.

Secondary: Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Primary Phase of the study.

Secondary: Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Booster Phase of the study.

Secondary: Titers of antibodies against poliovirus types 1, 2 and 3 (anti-1, anti-2 and anti-3) – Booster Phase of the study.

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

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

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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