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Clinical Trial Results:
A phase IIIb randomized, double-blind, controlled study to assess the safety, reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine compared to Prevenar, when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines as a 3-dose primary immunization course during the first 6 months of age

Summary
EudraCT number	2006-000557-21
Trial protocol	Outside EU/EEA
Global end of trial date	17 Oct 2007

Results information
Results version number	v2(current)
This version publication date	15 Dec 2022
First version publication date	26 Jul 2015
Other versions	v1
Version creation reason	Correction of full data set Correction of full data set and alignment between registries.

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

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Trial information

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Sponsor protocol code

107007

ISRCTN number

US NCT number

NCT00344318

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

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

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

22 Nov 2007

Is this the analysis of the primary completion data?

Yes

Primary completion date

27 Apr 2007

Global end of trial reached?

Yes

Global end of trial date

17 Oct 2007

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that the GSK Biologicals’ 10-valent pneumococcal conjugate (10Pn-PD-DiT) vaccine administered as a 3-dose primary vaccination course (either at 6-10-14 weeks or at 2-4-6 months of age), was non-inferior to Prevenar (7Pn) vaccine in terms of the incidence of post-immunization rectal fever greater than (>) 39.0°C, when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines.

Protection of trial subjects

All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.

Background therapy

Evidence for comparator

Actual start date of recruitment

07 Aug 2006

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Philippines: 400

Country: Number of subjects enrolled

Poland: 406

Worldwide total number of subjects

806

EEA total number of subjects

406

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)

806

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

Screening details

During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

Period 1 title

Overall (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

The study was conducted in a double-blind fashion. Due to the different appearance of the 10Pn-PD-DiT and Prevenar vaccines, an observer blind procedure (i.e. a different person than the one who performed safety assessments administered the vaccines) was followed in order to keep the study double-blind.

Are arms mutually exclusive

Yes

Synflorix 1 Group

Arm description

Subjects aged 6-12 weeks from the Philippines receiving Synflorix vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin vaccines at 6, 10, 14 weeks of age.

Arm type

Experimental

Investigational medicinal product name

Pneumococcal conjugate vaccine GSK1024850A

Investigational medicinal product code

Other name

10Pn-PD-DiT vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the right thigh at 6, 10, 14 weeks of age.

Investigational medicinal product name

Tritanrix-HepB

Investigational medicinal product code

Other name

DTPw-HBV

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the left thigh at 6, 10, 14 weeks of age, recombined with Hiberix.

Investigational medicinal product name

Hiberix

Investigational medicinal product code

Other name

Hib vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Reconstituted with Tritanrix-HepB before injection, 3 doses administered in the left thigh at 6, 10, 14 weeks of age.

Investigational medicinal product name

Polio Sabin

Investigational medicinal product code

Other name

OPV vaccine

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

3 oral doses at 6, 10, 14 weeks of age.

Synflorix 2 Group

Arm description

Subjects aged 6-12 weeks from Poland receiving Synflorix vaccine co-administered with Tritanrix-HepB/Hiberix and Poliorix vaccines at 2, 4, 6 months of age.

Arm type

Experimental

Investigational medicinal product name

Pneumococcal conjugate vaccine GSK1024850A

Investigational medicinal product code

Other name

10Pn-PD-DiT vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the right thigh at 2, 4, 6 months of age.

Investigational medicinal product name

Tritanrix-HepB

Investigational medicinal product code

Other name

DTPw-HBV

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the left thigh at 2, 4, 6 months of age, recombined with Hiberix.

Investigational medicinal product name

Hiberix

Investigational medicinal product code

Other name

Hib vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Reconstituted with Tritanrix-HepB before injection, 3 doses administered in the left thigh at 2, 4, 6 months of age.

Investigational medicinal product name

Poliorix

Investigational medicinal product code

Other name

IPV vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the lower left thigh at 2, 4, 6 months of age.

Prevenar 1 Group

Arm description

Subjects aged 6-12 weeks from the Philippines receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin at 6, 10, 14 weeks of age.

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

7Pn vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the right thigh at 6, 10, 14 weeks of age.

Investigational medicinal product name

Tritanrix-HepB

Investigational medicinal product code

Other name

DTPw-HBV vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the left thigh at 6, 10, 14 weeks of age, recombined with Hiberix.

Investigational medicinal product name

Hiberix

Investigational medicinal product code

Other name

Hib vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Reconstituted with Tritanrix-HepB before injection, 3 doses administered in the left thigh at 6, 10, 14 weeks of age.

Investigational medicinal product name

Polio Sabin

Investigational medicinal product code

Other name

OPV vaccine

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

3 doses at 6, 10, 14 weeks of age.

Prevenar 2 Group

Arm description

Subjects aged 6-12 weeks from Poland receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Poliorix at 2, 4, 6 months of age.

Arm type

Experimental

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

7Pn vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the right thigh at 2, 4, 6 months of age.

Investigational medicinal product name

Tritanrix-HepB

Investigational medicinal product code

Other name

DTPw-HBV vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the left thigh at 2, 4, 6 months of age, recombined with Hiberix.

Investigational medicinal product name

Hiberix

Investigational medicinal product code

Other name

Hib vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Reconstituted with Tritanrix-HepB before injection, 3 doses administered in the left thigh at 2, 4, 6 months of age.

Investigational medicinal product name

Poliorix

Investigational medicinal product code

Other name

IPV vaccines

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses administered in the lower left thigh at 2, 4, 6 months of age.

Number of subjects in period 1	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Started	300	303	100	103
Completed	296	298	99	100
Not completed	4	5	1	3
Consent withdrawn by subject	2	2	-	2
Adverse event, non-fatal	-	3	-	1
Lost to follow-up	2	-	1	-

Baseline characteristics

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Reporting group title

Synflorix 1 Group

Reporting group description

Subjects aged 6-12 weeks from the Philippines receiving Synflorix vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin vaccines at 6, 10, 14 weeks of age.

Reporting group title

Synflorix 2 Group

Reporting group description

Subjects aged 6-12 weeks from Poland receiving Synflorix vaccine co-administered with Tritanrix-HepB/Hiberix and Poliorix vaccines at 2, 4, 6 months of age.

Reporting group title

Prevenar 1 Group

Reporting group description

Subjects aged 6-12 weeks from the Philippines receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin at 6, 10, 14 weeks of age.

Reporting group title

Prevenar 2 Group

Reporting group description

Subjects aged 6-12 weeks from Poland receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Poliorix at 2, 4, 6 months of age.

Reporting group values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group	Total
Number of subjects	300	303	100	103	806
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	300	303	100	103	806
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0
From 65-84 years	0	0	0	0	0
85 years and over	0	0	0	0	0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	7.5 ( 1.64 )	7.4 ( 1.5 )	7.4 ( 1.53 )	7.5 ( 1.55 )	-
Gender categorical
Units: Subjects
Female	146	141	48	46	381
Male	154	162	52	57	425

End points

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Reporting group title

Synflorix 1 Group

Reporting group description

Subjects aged 6-12 weeks from the Philippines receiving Synflorix vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin vaccines at 6, 10, 14 weeks of age.

Reporting group title

Synflorix 2 Group

Reporting group description

Subjects aged 6-12 weeks from Poland receiving Synflorix vaccine co-administered with Tritanrix-HepB/Hiberix and Poliorix vaccines at 2, 4, 6 months of age.

Reporting group title

Prevenar 1 Group

Reporting group description

Subjects aged 6-12 weeks from the Philippines receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin at 6, 10, 14 weeks of age.

Reporting group title

Prevenar 2 Group

Reporting group description

Subjects aged 6-12 weeks from Poland receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Poliorix at 2, 4, 6 months of age.

Subject analysis set title

Synflorix Pooled Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

Synflorix 1 Group and Synflorix 2 Group pooled together.

Subject analysis set title

Prevenar Pooled Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

Prevenar 1 Group and Prevenar 2 Group pooled together.

Primary: Number of subjects reporting rectal temperature above (>) 39.0 degrees Celsius (°C)

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End point title

Number of subjects reporting rectal temperature above (>) 39.0 degrees Celsius (°C)

End point description

Fever was measured as rectal temperature. Assessment of occurrences of fever > 39.0 °C was performed post doses 1, 2 and 3 and across doses of Synflorix or Prevenar vaccine.

End point type

Primary

End point timeframe

Within 4 days (Days 0-3) after each dose and across doses

End point values	Synflorix Pooled Group	Prevenar Pooled Group
Number of subjects analysed	599	199
Units: Subjects
Fever > 39.0°C, post Dose 1 [N=598;199]	31	6
Fever > 39.0°C, post Dose 2 [N=594;199]	30	13
Fever > 39.0°C, post Dose 3 [N=594;199]	42	8
Fever > 39.0°C, across doses [N=599;199]	88	23

Rectal fever- Synflorix vs Prevenar- after Dose 1

Statistical analysis description

Analysis aimed to demonstrate that Synflorix administered as 3-dose primary vaccination course (either at 6-10-14 weeks or at 2-4-6 months of age), is non-inferior to Prevenar in terms of incidence of post-immunization rectal fever >39.0°C, when co-administered with Tritanrix-HepB/Hiberix and Polio Sabin or Poliorix vaccines. Standardized asymptotic 95% confidence interval (CI) for the difference in terms of percentages of subjects reporting rectal fever >39.0°C after Dose 1 was computed.

Comparison groups

Synflorix Pooled Group v Prevenar Pooled Group

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Difference in percentage

Point estimate

2.17

Confidence interval

level

95%

sides

2-sided

lower limit

-1.51

upper limit

4.88

Notes
[1] - Non-inferiority was demonstrated if the upper limit of the 95% CI of the difference (Synflorix minus Prevenar) in terms of percentage of subjects with rectal fever > 39.0°C is lower than 10%.

Rectal fever- Synflorix vs Prevenar - after Dose 2

Statistical analysis description

Analysis aimed to demonstrate that Synflorix administered as 3-dose primary vaccination course (either at 6-10-14 weeks or at 2-4-6 months of age), is non-inferior to Prevenar in terms of incidence of post-immunization rectal fever >39.0°C, when co-administered with Tritanrix-HepB/Hiberix and Polio Sabin or Poliorix vaccines. Standardized asymptotic 95% CI for the difference (Synflorix minus Prevenar) in terms of percentages of subjects reporting rectal fever >39.0°C after Dose 2 was computed.

Comparison groups

Synflorix Pooled Group v Prevenar Pooled Group

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Difference in percentage

Point estimate

-1.48

Confidence interval

level

95%

sides

2-sided

lower limit

-6.05

upper limit

1.92

Notes
[2] - Non-inferiority was demonstrated if the upper limit of the 95% CI of the difference (Synflorix minus Prevenar) in terms of percentage of subjects with rectal fever > 39.0°C is lower than 10%.

Rectal fever- Synflorix vs Prevenar - after Dose 3

Statistical analysis description

Analysis aimed to demonstrate that Synflorix administered as 3-dose primary vaccination course (either at 6-10-14 weeks or at 2-4-6 months of age), is non-inferior to Prevenar in terms of incidence of post-immunization rectal fever >39.0°C, when co-administered with Tritanrix-HepB/Hiberix and Polio Sabin or Poliorix vaccines. Standardized asymptotic 95% CI for the difference (Synflorix minus Prevenar) in terms of percentages of subjects reporting rectal fever >39.0°C after Dose 3 was computed.

Comparison groups

Synflorix Pooled Group v Prevenar Pooled Group

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Difference in percentage

Point estimate

3.05

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

6.19

Notes
[3] - Non-inferiority was demonstrated if the upper limit of the 95% CI of the difference (Synflorix minus Prevenar) in terms of percentage of subjects with rectal fever > 39.0°C is lower than 10%.

Rectal fever- Synflorix vs Prevenar - across doses

Statistical analysis description

Analysis aimed to demonstrate that Synflorix administered as 3-dose primary vaccination course (either at 6-10-14 weeks or at 2-4-6 months of age), is non-inferior to Prevenar in terms of incidence of post-immunization rectal fever >39.0°C, when co-administered with Tritanrix-HepB/Hiberix and Polio Sabin or Poliorix vaccines. Standardized asymptotic 95% CI for the difference (Synflorix minus Prevenar) in terms of percentages of subjects reporting rectal fever >39.0°C across doses was computed.

Comparison groups

Synflorix Pooled Group v Prevenar Pooled Group

Number of subjects included in analysis

798

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Difference in percentage

Point estimate

3.13

Confidence interval

level

95%

sides

2-sided

lower limit

-2.65

upper limit

8.01

Notes
[4] - Non-inferiority was demonstrated if the upper limit of the 95% CI of the difference (Synflorix minus Prevenar) in terms of percentage of subjects with rectal fever > 39.0°C is lower than 10%.

Secondary: Number of subjects with any and any Grade 3 solicited local symptoms

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End point title

Number of subjects with any and any Grade 3 solicited local symptoms

End point description

Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/spontaneously painful. Grade 3 swelling/redness was defined as swelling/redness larger than (>) 30 millimeters (mm). “Any” is defined as incidence of the specified symptom regardless of intensity.

End point type

Secondary

End point timeframe

Within 4 days (Days 0-3) after each dose and across doses

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	299	300	99	100
Units: Subjects
Any Pain, Post Dose 1 [N=299;299;99;100]	240	206	76	65
Grade 3 Pain, Post Dose 1 [N=299;299;99;100]	52	59	19	17
Any Redness, Post Dose 1 [N=299;299;99;100]	126	199	35	65
Grade 3 Redness, Post Dose 1 [N=299;299;99;100]	10	30	6	8
Any Swelling, Post Dose 1 [N=299;299;99;100]	142	153	39	56
Grade 3 Swelling, Post Dose 1 [N=299;299;99;100]	41	43	15	9
Any Pain, Post Dose 2 [N=296;299;99;100]	191	186	55	61
Grade 3 Pain, Post Dose 2 [N=296;299;99;100]	18	31	8	12
Any Redness, Post Dose 2 [N=296;299;99;100]	135	204	44	59
Grade 3 Redness, Post Dose 2 [N=296;299;99;100]	8	9	1	2
Any Swelling, Post Dose 2 [N=296;299;99;100]	98	163	29	51
Grade 3 Swelling, Post Dose 2 [N=296;299;99;100]	27	19	5	5
Any Pain, Post Dose 3 [N=296;298;99;100]	168	173	44	56
Grade 3 Pain, Post Dose 3 [N=296;298;99;100]	14	23	1	8
Any Redness, Post Dose 3 [N=296;298;99;100]	158	209	45	70
Grade 3 Redness, Post Dose 3 [N=296;298;99;100]	3	8	0	4
Any Swelling, Post Dose 3 [N=296;298;99;100]	84	151	25	53
Grade 3 Swelling, Post Dose 3 [N=296;298;99;100]	15	19	4	10
Any Pain, Across Doses [N=299;300;99;100]	258	255	82	89
Grade 3 Pain, Across Doses [N=299;300;99;100]	64	83	22	25
Any Redness, Across Doses [N=299;300;99;100]	221	265	67	90
Grade 3 Redness, Across Doses [N=299;300;99;100]	18	42	6	12
Any Swelling, Across Doses [N=299;300;99;100]	174	226	42	75
Grade 3 Swelling, Across Doses [N=299;300;99;100]	57	65	16	16

No statistical analyses for this end point

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms

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End point title

Number of subjects with any, Grade 3 and related solicited general symptoms

End point description

Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature >= 38.0°C), irritability, and loss of appetite. Grade 3 (G3) drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 (G3) fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 (G3) irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 (G3) loss of appetite was defined as the subject not eating at all. “Any” is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Related (REL) = Symptom assessed by the investigator as causally related to vaccination.

End point type

Secondary

End point timeframe

Within 4-days (Days 0-3) after each dose and across doses

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	299	300	99	100
Units: Subjects
Any Drowsiness, Dose 1 [N=299;299;99;100]	154	223	45	75
G3 Drowsiness, Dose 1 [N=299;299;99;100]	6	10	3	1
REL Drowsiness Dose 1 [N=299;299;99;100]	154	222	45	75
Any Fever, Dose 1 [N=299;299;99;100]	214	190	74	54
G3 Fever, Dose 1 [N=299;299;99;100]	0	0	0	0
REL Fever, Dose 1 [N=299;299;99;100]	214	190	74	54
Any Irritability, Dose 1 [N=299;299;99;100]	236	269	78	83
G3 Irritability, Dose 1 [N=299;299;99;100]	11	60	3	17
REL Irritability, Dose 1 [N=299;299;99;100]	236	266	78	83
Any Loss of appetite, Dose 1 [N=299;299;99;100]	104	166	26	52
G3 Loss of appetite, Dose 1 [N=299;299;99;100]	1	1	1	1
REL Loss of appetite, Dose 1 [N=299;299;99;100]	104	165	26	51
Any Drowsiness, Dose 2 [N=296;298;99;100]	102	172	25	57
G3 Drowsiness, Dose 2 [N=296;298;99;100]	1	9	1	2
REL Drowsiness, Dose 2 [N=296;298;99;100]	102	172	24	56
Any Fever, Dose 2 [N=296;298;99;100]	182	184	63	51
G3 Fever, Dose 2 [N=296;298;99;100]	0	0	0	0
REL Fever, Dose 2 [N=296;298;99;100]	182	184	63	50
Any Irritability, Dose 2 [N=296;298;99;100]	185	238	49	73
G3 Irritability, Dose 2 [N=296;298;99;100]	8	37	3	9
REL Irritability, Dose 2 [N=296;298;99;100]	185	237	48	72
Any Loss of appetite, Dose 2 [N=296;298;99;100]	66	117	20	28
G3 Loss of appetite, Dose 2 [N=296;298;99;100]	0	0	0	0
REL Loss of appetite, Dose 2 [N=296;298;99;100]	66	116	19	27
Any Drowsiness, Dose 3 [N=296;298;99;100]	90	152	25	41
G3 Drowsiness, Dose 3 [N=296;298;99;100]	2	5	0	0
REL Drowsiness, Dose 3 [N=296;298;99;100]	90	151	25	40
Any Fever, Dose 3 [N=296;298;99;100]	147	163	50	49
G3 Fever, Dose 3 [N=296;298;99;100]	0	0	0	1
REL Fever, Dose 3 [N=296;298;99;100]	147	162	50	49
Any Irritability, Dose 3 [N=296;298;99;100]	169	225	43	64
G3 Irritability, Dose 3 [N=296;298;99;100]	7	22	1	2
REL Irritability, Dose 3 [N=296;298;99;100]	169	223	43	64
Any Loss of appetite, Dose 3 [N=296;298;99;100]	61	113	19	19
G3 Loss of appetite, Dose 3 [N=296;298;99;100]	1	1	0	0
REL Loss of appetite, Dose 3 [N=296;298;99;100]	61	113	19	19
Any Drowsiness, Across Doses [N=299;300;99;100]	184	256	56	85
G3 Drowsiness, Across Doses [N=299;300;99;100]	9	17	3	3
REL Drowsiness, Across Doses [N=299;300;99;100]	184	256	56	85
Any Fever, Across Doses [N=299;300;99;100]	255	261	88	77
G3 Fever, Across Doses [N=299;300;99;100]	0	0	0	1
REL Fever, Across Doses [N=299;300;99;100]	255	261	88	77
Any Irritability, Across Doses [N=299;300;99;100]	258	289	82	93
G3 Irritability, Across Doses [N=299;300;99;100]	22	89	6	24
REL Irritability, Across Doses [N=299;300;99;100]	258	289	82	93
Any Loss of appetite, Across [N=299;300;99;100]	140	221	39	64
G3 Loss of appetite, Across [N=299;300;99;100]	1	2	1	1
REL Loss of appetite, Across [N=299;300;99;100]	140	220	39	63

No statistical analyses for this end point

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

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End point title

Number of subjects with unsolicited adverse events (AEs)

End point description

An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. “Any” is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination.

End point type

Secondary

End point timeframe

Within 31 days (Days 0-30) after each vaccination

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	300	303	100	103
Units: Subjects
Any unsolicited AE(s)	168	166	46	61

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

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

End point type

Secondary

End point timeframe

During the Active Phase: From Month 0 to Month 3 for Synflorix 1 Group and Prevenar 1 Group and from Month 0 to Month 5 for the Synflorix 2 Group and Prevenar 2 Group

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	300	303	100	103
Units: Subjects
Any SAEs	6	34	1	9

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

End point type

Secondary

End point timeframe

During the Extended Safety Follow-Up Phase: At Month 8 for Synflorix 1 Group and Prevenar 1 Group and at Month 10 for the Synflorix 2 Group and Prevenar 2 Group

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	300	303	100	103
Units: Subjects
Any SAEs	16	52	4	19

No statistical analyses for this end point

Secondary: Concentrations of antibodies against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

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End point title

Concentrations of antibodies against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

End point description

Seropositivity status, defined as Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥ 0.05 microgram per milliliter (µg/mL).

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	285	285	95	96
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 POST [N=285;285;94;96]	3.23 (2.94 to 3.54)	1.04 (0.94 to 1.15)	0.03 (0.03 to 0.04)	0.03 (0.03 to 0.03)
Anti-4 POST [N=285;285;95;96]	4.96 (4.46 to 5.51)	1.64 (1.49 to 1.8)	5.68 (4.94 to 6.53)	2.14 (1.88 to 2.44)
Anti-5 POST [N=285;285;95;96]	4.87 (4.5 to 5.26)	1.62 (1.48 to 1.78)	0.03 (0.03 to 0.04)	0.03 (0.03 to 0.03)
Anti-6B POST [N=285;285;95;96]	1.19 (1.02 to 1.38)	0.73 (0.64 to 0.84)	1.06 (0.8 to 1.4)	1.23 (0.96 to 1.58)
Anti-7F POST [N=285;285;95;96]	4.84 (4.45 to 5.27)	2.25 (2.07 to 2.45)	0.05 (0.04 to 0.06)	0.04 (0.03 to 0.04)
Anti-9V POST [N=285;285;95;96]	4.04 (3.66 to 4.46)	1.51 (1.37 to 1.66)	5.07 (4.32 to 5.96)	2.7 (2.32 to 3.14)
Anti-14 POST [N=285;285;95;96]	6.45 (5.65 to 7.38)	3.31 (2.98 to 3.68)	5.88 (4.71 to 7.34)	5.23 (4.39 to 6.24)
Anti-18C POST [N=285;285;95;96]	11.56 (10.22 to 13.08)	3.74 (3.28 to 4.28)	3.71 (3.14 to 4.38)	2.64 (2.25 to 3.11)
Anti-19F POST [N=285;285;95;96]	10.46 (9.32 to 11.74)	5.3 (4.77 to 5.89)	4.68 (4.02 to 5.45)	2.38 (2.04 to 2.78)
Anti-23F POST [N=285;285;95;96]	2.23 (1.98 to 2.5)	1.11 (0.98 to 1.26)	2.28 (1.7 to 3.06)	2.2 (1.83 to 2.65)

No statistical analyses for this end point

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.2 microgram per milliliter (µg/mL)

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End point title

Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.2 microgram per milliliter (µg/mL)

End point description

Cut-off values assessed were greater than or equal to 0.2 microgram per milliliter (µg/mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	285	285	95	96
Units: Subjects
Anti-1 POST [N=285;285;94;96]	285	280	3	3
Anti-4 POST [N=285;285;95;96]	283	282	95	96
Anti-5 POST [N=285;285;95;96]	285	282	3	2
Anti-6B POST [N=285;285;95;96]	260	244	82	91
Anti-7F POST [N=285;285;95;96]	284	285	9	5
Anti-9V POST [N=285;285;95;96]	284	285	95	96
Anti-14 POST [N=285;285;95;96]	285	285	95	96
Anti-18C POST [N=285;285;95;96]	284	281	95	95
Anti-19F POST [N=285;285;95;96]	285	282	94	95
Anti-23F POST [N=285;285;95;96]	277	269	90	95

No statistical analyses for this end point

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.05 microgram per liter (µg/mL)

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End point title

Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.05 microgram per liter (µg/mL)

End point description

Cut-off values assessed were greater than or equal to 0.05 microgram per liter (µg/mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	285	285	95	96
Units: Subjects
Anti-1 POST [N=285;285;94;96]	285	285	20	13
Anti-4 POST [N=285;285;95;96]	285	285	95	96
Anti-5 POST [N=285;285;95;96]	285	285	19	13
Anti-6B POST [N=285;285;95;96]	279	274	92	91
Anti-7F POST [N=285;285;95;96]	285	285	37	22
Anti-9V POST [N=285;285;95;96]	285	285	95	96
Anti-14 POST [N=285;285;95;96]	285	285	95	96
Anti-18C POST [N=285;285;95;96]	284	285	95	95
Anti-19F POST [N=285;285;95;96]	285	285	95	95
Anti-23F POST [N=285;285;95;96]	285	279	91	96

No statistical analyses for this end point

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

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End point title

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

End point description

Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	142	145	46	49
Units: Titers
geometric mean (confidence interval 95%)
OPA Anti-1 [N=142;144;46;49]	93.7 (68.2 to 128.7)	14.8 (11.2 to 19.6)	4.2 (3.8 to 4.5)	4 (4 to 4)
OPA Anti-4 [N=138;145;43;49]	1008.7 (849.1 to 1198.4)	602.9 (494.8 to 734.6)	1229.9 (975.5 to 1550.7)	513 (388.2 to 677.9)
OPA Anti-5 [N=140;144;46;49]	209.3 (176.6 to 248)	67.2 (52.2 to 86.6)	4 (4 to 4)	4 (4 to 4)
OPA Anti-6B [N=142;145;43;49]	963.5 (714.7 to 1299)	361.9 (255 to 513.7)	1762.2 (975.3 to 3184)	805 (436.9 to 1483.4)
OPA Anti-7F [N=137;144;44;49]	5196.4 (4349.2 to 6208.6)	2002.2 (1543.1 to 2597.9)	14.2 (6.9 to 29.4)	6.9 (4.3 to 11.1)
OPA Anti-9V [N=130;144;43;49]	1631.9 (1343.8 to 1981.9)	1171.7 (966.1 to 1421.1)	1713.3 (1294.6 to 2267.5)	1166 (782.6 to 1737.2)
OPA Anti-14 [N=142;145;46;49]	1669.1 (1267.7 to 2197.6)	640 (520.2 to 787.5)	2117.4 (1210.9 to 3702.6)	947.6 (658.6 to 1363.4)
OPA Anti-18C [N=139;144;45;49]	673.3 (569.7 to 795.8)	174.9 (137.1 to 223.1)	283.7 (209.6 to 384.1)	127 (86.4 to 186.5)
OPA Anti-19F [N=139;143;46;49]	1121.7 (931.5 to 1350.6)	337.8 (262.9 to 434.1)	81.6 (53 to 125.5)	35.9 (25.7 to 50.1)
OPA Anti-23F [N=141;143;43;49]	2186.6 (1845.4 to 2590.9)	920.6 (678 to 1249.9)	4126.6 (2609 to 6526.8)	3895.4 (2842.8 to 5337.8)

No statistical analyses for this end point

Secondary: Number of subjects with opsonophagocytic activity (OPA) against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F equal to or above (>=) 8

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End point title

Number of subjects with opsonophagocytic activity (OPA) against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F equal to or above (>=) 8

End point description

Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C , 19F and 23F >= 8.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	142	145	46	49
Units: Subjects
OPA Anti-1 [N=142;144;46;49]	117	62	1	0
OPA Anti-4 [N=138;145;43;49]	137	143	43	49
OPA Anti-5 [N=140;144;46;49]	139	127	0	0
OPA Anti-6B [N=142;145;43;49]	132	122	40	44
OPA Anti-7F [N=137;144;44;49]	137	141	10	5
OPA Anti-9V [N=130;144;43;49]	130	144	43	49
OPA Anti-14 [N=142;145;46;49]	138	142	43	48
OPA Anti-18C [N=139;144;45;49]	138	137	45	48
OPA Anti-19F [N=139;143;46;49]	137	142	42	45
OPA Anti-23F [N=141;143;43;49]	141	132	42	49

No statistical analyses for this end point

Secondary: Concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A

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End point title

Concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A

End point description

Seropositivity status, defined as Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations >= 0.05 microgram per milliliter (µg/mL).

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	285	285	95	96
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A [N=285;285;95;96]	0.3 (0.26 to 0.35)	0.17 (0.15 to 0.2)	0.23 (0.18 to 0.3)	0.26 (0.2 to 0.33)
Anti-19A [N=285;284;95;96]	0.36 (0.31 to 0.41)	0.29 (0.25 to 0.34)	0.18 (0.15 to 0.22)	0.12 (0.1 to 0.15)

No statistical analyses for this end point

Secondary: Number of subjects with concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 0.05 microgram per milliliter (μg/mL)

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End point title

Number of subjects with concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 0.05 microgram per milliliter (μg/mL)

End point description

Cut-off values assessed were greater than or equal to 0.05 microgram per milliliter (μg/mL) in the sera of subjects seronegative before vaccination.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	285	285	95	96
Units: Subjects
Anti-6A [N=285;285;95;96]	261	230	84	84
Anti-19A [N=285;284;95;96]	269	264	90	83

No statistical analyses for this end point

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

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End point title

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

End point description

Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A >= 8.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	137	143	44	49
Units: Titers
geometric mean (confidence interval 95%)
OPA Anti-6A [N=127;137;43;48]	93.1 (64.1 to 135.2)	60.5 (40.7 to 89.9)	137.3 (69.7 to 270.3)	175.1 (87.2 to 351.6)
OPA Anti-19A [N=137;143;44;49]	10.6 (7.9 to 14.2)	10.1 (7.8 to 13.1)	4.2 (3.8 to 4.7)	4 (4 to 4)

No statistical analyses for this end point

Secondary: Number of subjects with opsonophagocytic activity (OPA) against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 8

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End point title

Number of subjects with opsonophagocytic activity (OPA) against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 8

End point description

Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A >= 8.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	137	143	44	49
Units: Subjects
OPA Anti-6A [N=127;137;43;48]	91	83	34	36
OPA Anti-19A [N=137;143;44;49]	35	41	1	0

No statistical analyses for this end point

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

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End point title

Concentrations of antibodies against protein D (Anti-PD)

End point description

Seropositivity status, defined as Anti-PD antibody concentrations >= 100 ELISA units per milliliter ( EL.U/mL).

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	284	285	95	96
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD	3800 (3481.2 to 4148)	2002 (1780 to 2251.6)	105.2 (85.3 to 129.6)	66.6 (58.5 to 75.8)

No statistical analyses for this end point

Secondary: Number of subjects with concentrations of antibodies against protein D (Anti-PD) equal to or above (>=) 100 ELISA units per milliliter (EL.U/mL)

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End point title

Number of subjects with concentrations of antibodies against protein D (Anti-PD) equal to or above (>=) 100 ELISA units per milliliter (EL.U/mL)

End point description

Cut-off values assessed were greater than or equal to 100 ELISA units per milliliter (EL.U/mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Synflorix or Prevenar

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	284	285	95	96
Units: Subjects
Anti-PD	284	285	39	18

No statistical analyses for this end point

Secondary: Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 0.15 microgram per milliliter (µg/ mL)

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End point title

Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 0.15 microgram per milliliter (µg/ mL)

End point description

Cut-off values assessed were greater than or equal to 0.15 microgram per milliliter (µg/ mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	140	49	47
Units: Subjects
Anti-PRP	140	140	49	47

No statistical analyses for this end point

Secondary: Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 1.0 microgram per milliliter (µg/mL)

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End point title

Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 1.0 microgram per milliliter (µg/mL)

End point description

Cut-off values assessed were greater than or equal to 1.0 microgram per milliliter (µg/mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	140	49	47
Units: Subjects
Anti-PRP	139	137	48	45

No statistical analyses for this end point

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

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End point title

Anti-polyribosyl-ribitol-phosphate (Anti-PRP) antibody concentrations

End point description

Seroprotection status, defined as Anti-PRP antibody concentrations >= 0.15 µg/mL and >= 1.0 µg/mL.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	140	49	47
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP	26.001 (21.196 to 31.894)	9.376 (7.941 to 11.071)	25.758 (17.669 to 37.548)	8.86 (6.87 to 11.427)

No statistical analyses for this end point

Secondary: Number of subjects with anti-diphtheria (Anti D) and anti-tetanus toxoids (Anti TT) antibody concentrations equal to or above 0.1 International Units per milliliter (IU/mL)

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End point title

Number of subjects with anti-diphtheria (Anti D) and anti-tetanus toxoids (Anti TT) antibody concentrations equal to or above 0.1 International Units per milliliter (IU/mL)

End point description

Cut-off values assessed were greater than or equal to 0.1 International Units per milliliter (IU/mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	140	49	47
Units: Subjects
Anti-diphtheria [N=140;140;49;47]	137	140	49	46
Anti-tetanus [N=139;140;48;47]	139	140	48	47

No statistical analyses for this end point

Secondary: Anti-diphtheria (Anti-D) and anti-tetanus toxoids (Anti-TT) antibody concentrations

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End point title

Anti-diphtheria (Anti-D) and anti-tetanus toxoids (Anti-TT) antibody concentrations

End point description

Seroprotection status, defined as Anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations >= 0.1 IU/mL.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	140	49	47
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-diphtheria [N=140;140;49;47]	1.735 (1.468 to 2.052)	1.549 (1.356 to 1.771)	1.252 (0.97 to 1.616)	1.039 (0.786 to 1.375)
Anti-tetanus [N=139;140;48;47]	5.195 (4.508 to 5.985)	3.505 (3.148 to 3.904)	3.476 (2.637 to 4.583)	2.659 (2.091 to 3.381)

No statistical analyses for this end point

Secondary: Number of subjects with anti-Hepatitis B surface antigen (HBs) antibody concentrations equal to or above 10 milli-International Units per milliliter (mIU/mL)

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End point title

Number of subjects with anti-Hepatitis B surface antigen (HBs) antibody concentrations equal to or above 10 milli-International Units per milliliter (mIU/mL)

End point description

Cut-off values assessed were greater than or equal to 10 milli-International Units per milliliter (mIU/mL) in the sera of subjects.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	133	49	44
Units: Subjects
Anti-HBs	127	132	44	44

No statistical analyses for this end point

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

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End point title

Anti-hepatitis B surface antigen (HBs) antibody concentrations

End point description

Seroprotection status, defined as Anti-HBs antibody concentrations >= 10 mIU/mL.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	140	133	49	44
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs	101.6 (79.7 to 129.5)	756.7 (640.4 to 894.3)	129.8 (83.3 to 202.1)	792.2 (585.2 to 1072.2)

No statistical analyses for this end point

Secondary: Number of subjects with anti-polio type 1, 2 and 3 antibody titers equal to or above (>=) 8

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End point title

Number of subjects with anti-polio type 1, 2 and 3 antibody titers equal to or above (>=) 8

End point description

Titers were expressed as geometric mean titres (GMTs).

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	124	120	44	41
Units: Subjects
Anti-polio 1 [N=123;120;44;40]	120	120	40	40
Anti-polio 2 [N=124;116;43;41]	124	115	43	41
Anti-polio 3 [N=120;108;38;39]	116	107	32	39

No statistical analyses for this end point

Secondary: Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers

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End point title

Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers

End point description

Seroprotection status, defined as Anti-polio type 1, Anti-polio type 2 and Anti-polio type 3 antibody titers >= 8.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	124	120	44	41
Units: Titers
geometric mean (confidence interval 95%)
Anti-polio 1 [N=123;120;44;40]	641.5 (485.7 to 847.3)	331.1 (269.5 to 406.8)	373.7 (207.4 to 673.4)	267.6 (187.5 to 381.8)
Anti-polio 2 [N=124;116;43;41]	523.6 (436.9 to 627.5)	276.8 (223 to 343.5)	546.2 (370.5 to 805.2)	303.5 (207.1 to 444.8)
Anti-polio 3 [N=120;108;38;39]	204.5 (164.3 to 254.5)	540.8 (433.7 to 674.3)	101.9 (59.5 to 174.5)	611.5 (449.4 to 832.2)

No statistical analyses for this end point

Secondary: Number of subjects with anti-Bordetella pertussis (anti-BPT) antibody concentrations equal to or above 15 ELISA unit per milli-liter (EL.U/mL) (seropositivity)

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End point title

Number of subjects with anti-Bordetella pertussis (anti-BPT) antibody concentrations equal to or above 15 ELISA unit per milli-liter (EL.U/mL) (seropositivity)

End point description

Cut-off values assessed were greater than or equal to 15 ELISA unit per milli-liter (EL.U/mL) in the sera of subjects seronegative before vaccination.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	138	133	48	45
Units: Subjects
Anti-BPT	137	126	47	42

No statistical analyses for this end point

Secondary: Anti-Bordetella pertussis (anti-BPT) antibody concentrations

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End point title

Anti-Bordetella pertussis (anti-BPT) antibody concentrations

End point description

Seropositivity status, defined as Anti-BPT antibody concentrations >= 15 EL.U/mL.

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	138	133	48	45
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-BPT	72.465 (65.787 to 79.82)	53.481 (47.215 to 60.579)	77.175 (64.433 to 92.435)	60.003 (46.394 to 77.604)

No statistical analyses for this end point

Secondary: Number of subjects with vaccine response to Bordetella pertussis

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End point title

Number of subjects with vaccine response to Bordetella pertussis

End point description

Vaccine response to B. pertussis; defined as appearance of antibodies in subjects initially seronegative (S-) (i.e., concentrations < 15 EL.U/mL) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (S+) (i.e., with concentrations >= 15 EL.U/mL).

End point type

Secondary

End point timeframe

One month after the administration of the 3rd vaccine dose of Tritanrix-HepB/Hiberix + Polio Sabin or Poliorix

End point values	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Number of subjects analysed	128	119	46	41
Units: Subjects
S- (N=128;119;46;41)	127	112	46	38
S+ (N=9;14;2;4)	9	12	1	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited local and general symptoms: During the 4 days post vaccination Unsolicited AEs: During the 31 days post vaccination; SAEs: From study Day 0 until the 6-month extended safety follow-up.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

13.0

Reporting group title

Synflorix 1 Group

Reporting group description

Subjects aged 6-12 weeks from the Philippines receiving Synflorix vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin vaccines at 6, 10, 14 weeks of age.

Reporting group title

Synflorix 2 Group

Reporting group description

Subjects aged 6-12 weeks from Poland receiving Synflorix vaccine co-administered with Tritanrix-HepB/Hiberix and Poliorix vaccines at 2, 4, 6 months of age.

Reporting group title

Prevenar 1 Group

Reporting group description

Subjects aged 6-12 weeks from the Philippines receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Polio Sabin at 6, 10, 14 weeks of age.

Reporting group title

Prevenar 2 Group

Reporting group description

Subjects aged 6-12 weeks from Poland receiving the Prevenar vaccine, co-administered with Tritanrix-HepB/Hiberix and Poliorix at 2, 4, 6 months of age.

Serious adverse events	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Total subjects affected by serious adverse events
subjects affected / exposed	16 / 300 (5.33%)	52 / 303 (17.16%)	4 / 100 (4.00%)	19 / 103 (18.45%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
General disorders and administration site conditions
Pyrexia
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 300 (0.33%)	1 / 303 (0.33%)	0 / 100 (0.00%)	1 / 103 (0.97%)
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
Ill-defined disorder
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	0 / 303 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)
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
Immune system disorders
Milk allergy
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 300 (0.67%)	0 / 303 (0.00%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	2 / 303 (0.66%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis chronic
subjects affected / exposed	0 / 300 (0.00%)	3 / 303 (0.99%)	0 / 100 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Hepatic enzyme increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	0 / 303 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Contusion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Head injury
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Atrial septal defect
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Double ureter
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Nervous system disorders
Febrile convulsion
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	2 / 303 (0.66%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Microcytic anaemia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Thrombocytopenic purpura
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	0 / 303 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	2 / 303 (0.66%)	0 / 100 (0.00%)	3 / 103 (2.91%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	4 / 303 (1.32%)	0 / 100 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	3 / 303 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aphthous stomatitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Dyspepsia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Enteritis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Gastritis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis atopic
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	0 / 303 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)
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
Rash
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 300 (0.33%)	0 / 303 (0.00%)	0 / 100 (0.00%)	0 / 103 (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
Renal and urinary disorders
Nephrotic syndrome
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	14 / 303 (4.62%)	0 / 100 (0.00%)	2 / 103 (1.94%)
occurrences causally related to treatment / all	0 / 0	0 / 16	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
alternative assessment type: Non-systematic
subjects affected / exposed	7 / 300 (2.33%)	8 / 303 (2.64%)	1 / 100 (1.00%)	3 / 103 (2.91%)
occurrences causally related to treatment / all	0 / 7	0 / 8	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
alternative assessment type: Non-systematic
subjects affected / exposed	5 / 300 (1.67%)	9 / 303 (2.97%)	2 / 100 (2.00%)	2 / 103 (1.94%)
occurrences causally related to treatment / all	0 / 5	0 / 9	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	3 / 303 (0.99%)	0 / 100 (0.00%)	3 / 103 (2.91%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	4 / 303 (1.32%)	1 / 100 (1.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	3 / 303 (0.99%)	0 / 100 (0.00%)	2 / 103 (1.94%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 300 (0.67%)	0 / 303 (0.00%)	0 / 100 (0.00%)	2 / 103 (1.94%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	3 / 303 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	1 / 103 (0.97%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	2 / 303 (0.66%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	2 / 303 (0.66%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhinitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	2 / 303 (0.66%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 300 (0.33%)	0 / 303 (0.00%)	0 / 100 (0.00%)	0 / 103 (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
Gastrointestinal infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Laryngitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Paronychia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Pneumonia mycoplasmal
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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
Urosepsis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	0 / 303 (0.00%)	0 / 100 (0.00%)	1 / 103 (0.97%)
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
Metabolism and nutrition disorders
Dehydration
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 300 (0.67%)	0 / 303 (0.00%)	2 / 100 (2.00%)	0 / 103 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Iron deficiency
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	1 / 303 (0.33%)	0 / 100 (0.00%)	0 / 103 (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: 2%

Non-serious adverse events	Synflorix 1 Group	Synflorix 2 Group	Prevenar 1 Group	Prevenar 2 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	296 / 300 (98.67%)	300 / 303 (99.01%)	95 / 100 (95.00%)	98 / 103 (95.15%)
Vascular disorders
Haematoma
subjects affected / exposed	11 / 300 (3.67%)	0 / 303 (0.00%)	1 / 100 (1.00%)	0 / 103 (0.00%)
occurrences all number	11	0	1	0
Nervous system disorders
Somnolence
subjects affected / exposed	184 / 300 (61.33%)	256 / 303 (84.49%)	56 / 100 (56.00%)	85 / 103 (82.52%)
occurrences all number	346	547	95	173
General disorders and administration site conditions
Pain
subjects affected / exposed	258 / 300 (86.00%)	86 / 303 (28.38%)	82 / 100 (82.00%)	89 / 103 (86.41%)
occurrences all number	599	193	175	182
Swelling
subjects affected / exposed	174 / 300 (58.00%)	226 / 303 (74.59%)	42 / 100 (42.00%)	75 / 103 (72.82%)
occurrences all number	324	467	93	160
Pyrexia
subjects affected / exposed	255 / 300 (85.00%)	262 / 303 (86.47%)	88 / 100 (88.00%)	77 / 103 (74.76%)
occurrences all number	543	542	187	155
Gastrointestinal disorders
Diarrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 300 (0.00%)	7 / 303 (2.31%)	0 / 100 (0.00%)	8 / 103 (7.77%)
occurrences all number	0	10	0	9
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	221 / 300 (73.67%)	265 / 303 (87.46%)	67 / 100 (67.00%)	91 / 103 (88.35%)
occurrences all number	420	360	124	195
Psychiatric disorders
Irritability
subjects affected / exposed	258 / 300 (86.00%)	289 / 303 (95.38%)	82 / 100 (82.00%)	93 / 103 (90.29%)
occurrences all number	590	732	170	221
Infections and infestations
Upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	84 / 300 (28.00%)	16 / 303 (5.28%)	25 / 100 (25.00%)	12 / 103 (11.65%)
occurrences all number	97	17	31	13
Rhinitis
alternative assessment type: Non-systematic
subjects affected / exposed	38 / 300 (12.67%)	39 / 303 (12.87%)	7 / 100 (7.00%)	9 / 103 (8.74%)
occurrences all number	42	43	10	9
Bronchitis
alternative assessment type: Non-systematic
subjects affected / exposed	9 / 300 (3.00%)	6 / 303 (1.98%)	0 / 100 (0.00%)	6 / 103 (5.83%)
occurrences all number	9	6	0	7
Gastroenteritis
alternative assessment type: Non-systematic
subjects affected / exposed	17 / 300 (5.67%)	3 / 303 (0.99%)	7 / 100 (7.00%)	0 / 103 (0.00%)
occurrences all number	19	3	7	0
Pharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	4 / 300 (1.33%)	17 / 303 (5.61%)	2 / 100 (2.00%)	3 / 103 (2.91%)
occurrences all number	4	18	2	4
Nasopharyngitis
subjects affected / exposed	0 / 300 (0.00%)	3 / 303 (0.99%)	0 / 100 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	4	0	0
Urinary tract infection
subjects affected / exposed	0 / 300 (0.00%)	4 / 303 (1.32%)	1 / 100 (1.00%)	1 / 103 (0.97%)
occurrences all number	0	4	1	1
Viral infection
subjects affected / exposed	11 / 300 (3.67%)	1 / 303 (0.33%)	4 / 100 (4.00%)	0 / 103 (0.00%)
occurrences all number	11	1	4	0
Viral rhinitis
subjects affected / exposed	15 / 300 (5.00%)	0 / 303 (0.00%)	2 / 100 (2.00%)	0 / 103 (0.00%)
occurrences all number	16	0	2	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	140 / 300 (46.67%)	79 / 303 (26.07%)	39 / 100 (39.00%)	64 / 103 (62.14%)
occurrences all number	231	152	65	99

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Were there any global substantial amendments to the protocol? Yes

06 Jul 2006

Amendment 1 This study is designed to evaluate safety, reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine compared to the licensed vaccine Prevenar when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines. Both the immunization schedule for infants recommended by the WHO Expanded Programme on Immunization (EPI: 6, 10, 14 weeks of age) and a 2-4-6 months of age schedule were evaluated. Incidence of fever is increased in infants following co-administration of the pneumococcal vaccine with standard infant vaccines when compared to infants that received either pneumococcal vaccine or standard vaccines separately. Therefore, this study evaluated and compared the incidence of rectal fever >39.0°C for both pneumococcal conjugate vaccines. Immune response of the vaccines, when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines, were also assessed according to the 2 different schedules.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects reporting rectal temperature above (>) 39.0 degrees Celsius (°C)

Primary: Number of subjects reporting rectal temperature above (>) 39.0 degrees Celsius (°C)

Secondary: Number of subjects with any and any Grade 3 solicited local symptoms

Secondary: Number of subjects with any and any Grade 3 solicited local symptoms

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms

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

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

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

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

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

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

Secondary: Concentrations of antibodies against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

Secondary: Concentrations of antibodies against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.2 microgram per milliliter (µg/mL)

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.2 microgram per milliliter (µg/mL)

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.05 microgram per liter (µg/mL)

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations equal to or above (>=) 0.05 microgram per liter (µg/mL)

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

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

Secondary: Number of subjects with opsonophagocytic activity (OPA) against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F equal to or above (>=) 8

Secondary: Number of subjects with opsonophagocytic activity (OPA) against vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F equal to or above (>=) 8

Secondary: Concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A

Secondary: Concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A

Secondary: Number of subjects with concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 0.05 microgram per milliliter (μg/mL)

Secondary: Number of subjects with concentrations of antibodies against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 0.05 microgram per milliliter (μg/mL)

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

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

Secondary: Number of subjects with opsonophagocytic activity (OPA) against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 8

Secondary: Number of subjects with opsonophagocytic activity (OPA) against cross-reactive pneumococcal serotypes 6A and 19A equal to or above (>=) 8

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

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

Secondary: Number of subjects with concentrations of antibodies against protein D (Anti-PD) equal to or above (>=) 100 ELISA units per milliliter (EL.U/mL)

Secondary: Number of subjects with concentrations of antibodies against protein D (Anti-PD) equal to or above (>=) 100 ELISA units per milliliter (EL.U/mL)

Secondary: Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 0.15 microgram per milliliter (µg/ mL)

Secondary: Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 0.15 microgram per milliliter (µg/ mL)

Secondary: Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 1.0 microgram per milliliter (µg/mL)

Secondary: Number of subjects with anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentration equal to or above 1.0 microgram per milliliter (µg/mL)

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

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

Secondary: Number of subjects with anti-diphtheria (Anti D) and anti-tetanus toxoids (Anti TT) antibody concentrations equal to or above 0.1 International Units per milliliter (IU/mL)

Secondary: Number of subjects with anti-diphtheria (Anti D) and anti-tetanus toxoids (Anti TT) antibody concentrations equal to or above 0.1 International Units per milliliter (IU/mL)

Secondary: Anti-diphtheria (Anti-D) and anti-tetanus toxoids (Anti-TT) antibody concentrations

Secondary: Anti-diphtheria (Anti-D) and anti-tetanus toxoids (Anti-TT) antibody concentrations

Secondary: Number of subjects with anti-Hepatitis B surface antigen (HBs) antibody concentrations equal to or above 10 milli-International Units per milliliter (mIU/mL)

Secondary: Number of subjects with anti-Hepatitis B surface antigen (HBs) antibody concentrations equal to or above 10 milli-International Units per milliliter (mIU/mL)

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

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

Secondary: Number of subjects with anti-polio type 1, 2 and 3 antibody titers equal to or above (>=) 8

Secondary: Number of subjects with anti-polio type 1, 2 and 3 antibody titers equal to or above (>=) 8

Secondary: Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers

Secondary: Anti-polio type 1, 2 and 3 (Anti-Polio 1, 2 and 3) antibody titers

Secondary: Number of subjects with anti-Bordetella pertussis (anti-BPT) antibody concentrations equal to or above 15 ELISA unit per milli-liter (EL.U/mL) (seropositivity)

Secondary: Number of subjects with anti-Bordetella pertussis (anti-BPT) antibody concentrations equal to or above 15 ELISA unit per milli-liter (EL.U/mL) (seropositivity)

Secondary: Anti-Bordetella pertussis (anti-BPT) antibody concentrations

Secondary: Anti-Bordetella pertussis (anti-BPT) antibody concentrations

Secondary: Number of subjects with vaccine response to Bordetella pertussis

Secondary: Number of subjects with vaccine response to Bordetella pertussis

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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