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Clinical Trial Results:
A phase IIIb randomised, open, controlled study to assess the safety, reactogenicity and immunogenicity of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine when co-administered with DTPa-combined, MenC and Hib-MenC vaccines in children as a 3-dose primary immunization course during the first 6 months of age.

Summary
EudraCT number	2006-000558-30
Trial protocol	DE ES
Global end of trial date	24 Oct 2007

Results information
Results version number	v1(current)
This version publication date	07 Mar 2016
First version publication date	12 Jun 2015
Other versions

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

107005

ISRCTN number

US NCT number

NCT00334334

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

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

Public contact

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

Scientific contact

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

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

27 Nov 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

23 Apr 2007

Global end of trial reached?

Yes

Global end of trial date

24 Oct 2007

Was the trial ended prematurely?

Main objective of the trial

The main objective of the study is to demonstrate that GSK Biologicals’ 10-valent pneumococcal conjugate vaccine, when administered as a 3-dose primary vaccination course, is non-inferior to Prevenar, both co-administered with DTPa-HBV-IPV and Hib-MenC vaccines, in terms of post-immunization febrile reactions with rectal fever > 39.0°C. Criteria for safety: Non-inferiority will be demonstrated if the upper limit of the 95% CI of the difference (10Pn-PD-DiT + Hib-MenC Group minus Prevenar Group), in terms of percentage of subjects with rectal fever >39.0°C, is lower than 10%.

Protection of trial subjects

Vaccines were administered by qualified and trained personnel and only to eligible subjects that had no contraindications to any components of the vaccines. In addition, specific adverse events (AEs) constituted absolute contraindications to further vaccination; if occurring, the subject did not receive additional doses of vaccine, continued other study procedures at the discretion of the investigator and was followed until resolution of the AE. AEs motivating ending of vaccination were any anaphylactic reaction post vaccination, acute disease at time of vaccination (= presence of moderate or severe illness with/without fever; vaccines were given in case of minor illnesses like diarrhea or mild upper respiratory infection with/without low-grade fever [i.e. Oral/Axillary/Tympanic temperature (T) < 37.5°C/Rectal T < 38.0°C] with visit postponed until improvement) and febrile illness (= oral, axillary or tympanic T ≥ 37.5°C, rectal T ≥ 38.0°C – T >= these cut-offs warranted deferral of vaccination pending recovery). Also, for the DTPa-HBV-IPV/Hib or DTPa-HBV-IPV vaccine, experience of encephalopathy (= acute, severe central nervous system disorder within 7 days post vaccination lasting more than a few hours, with failure to recover within 24 hours) constituted absolute contraindications to vaccination. For these vaccines, specific precautions were taken in case of rectal T ≥ 40.5°C or oral, axillary or tympanic T ≥ 40.0°C within 48 hours of vaccination, collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of vaccination, persistent, inconsolable crying within 48 hours of vaccination and lasting ≥ 3 hours and seizures with/without fever occurring within 3 days of vaccination. For Prevenar, moderate to severe illness, with/without fever was a reason to defer immunization. For NeisVac-C and Meningitec, vaccines were given with caution to individuals with thrombocytopenia or any coagulation disorder.

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Jun 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

Spain: 519

Country: Number of subjects enrolled

Germany: 413

Country: Number of subjects enrolled

Poland: 640

Worldwide total number of subjects

1572

EEA total number of subjects

1572

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)

1572

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

The study included an Active Phase, till about 7 months of age, and an Extended Safety Follow-Up (ESFU) Phase, till about 12 months of age.

Screening details

1572 subjects were enrolled in the study and vaccinated out of which 24 subjects from a center located in Germany (6 in each group) were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit; Safety results for these subjects are reported in this summary.

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

GSK 1024850A + Meningitec™ Group

Arm description

Subjects were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). In addition, subjects also received Wyeth’s Men-C conjugate vaccine (Meningitec™, also referred to as Men vaccine) at 2 and 4 months of age. For subjects in Poland and to comply with national recommendations, subjects were also offered a third dose of Meningitec™ at approximately 7 months of age, after the blood sampling performed at that time point. All vaccines were administered intramuscularly (IM), 10Pn in the right thigh, Infanrix™ hexa in the upper left thigh and Meningitec™ in the lower left thigh.

Arm type

Experimental

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn, 10Pn-PD-DiT, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Three doses of the vaccine were administered intramuscularly, in the lower left thigh at 2, 4 and 6 months of age.

Investigational medicinal product name

Infanrix™ Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses were administered intramuscularly in the lower left thigh at 2 and 4 months of age. Subjects in Poland, to comply with national recommendations, were also offered a third dose at approximately 7 months of age, after blood sampling.

Investigational medicinal product name

Meningitec™

Investigational medicinal product code

Other name

Wyeth’s conjugated meningococcal C vaccine, Meningitec™

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

One dose of the vaccine was administered, in the lower left thigh or deltoid.

GSK 1024850A + NeisVac-C™ Group

Arm description

Subjects were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). In addition, subjects also received Baxter’s Men-C conjugate vaccine (NeisVac-C™, also referred to as Neis vaccine) at 2 and 4 months of age. For subjects in Poland and to comply with national recommendations, subjects were also offered a third dose of NeisVac-C™, at approximately 7 months of age, after the blood sampling performed at that time point. All vaccines were administered intramuscularly (IM), 10Pn in the right thigh, Infanrix™ hexa in the upper left thigh and NeisVac-C™, in the lower left thigh.

Arm type

Experimental

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn, 10Pn-PD-DiT, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Three doses of the vaccine were administered intramuscularly, in the lower left thigh at 2, 4 and 6 months of age.

Investigational medicinal product name

Infanrix™ Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

NeisVac-C

Investigational medicinal product code

Other name

Baxter's meningococcal C conjugate vaccine, NeisVac-C™

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

One dose of the vaccine was administered, in the lower left thigh or deltoid.

GSK 1024850A + Menitorix™ Group

Arm description

The Group is also referred to as the 10Pn-PD-DiT + Hib-MenC Group and included subjects who were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ pent (also referred to as DTPa-HBV-IPV) and with Menitorix™ (HibMenC). All vaccines were administered intramuscularly (IM), 10Pn in the right thigh, Infanrix™ penta in the upper left thigh and Menitorix™ in the lower left thigh.

Arm type

Experimental

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn, 10Pn-PD-DiT, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine, GSK1024850A

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Three doses of the vaccine were administered intramuscularly, in the lower left thigh at 2, 4 and 6 months of age.

Investigational medicinal product name

Infanrix penta

Investigational medicinal product code

Other name

DTPa-HBV-IPV, Infanrix™ penta

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Menitorix

Investigational medicinal product code

Other name

GSK Biologicals’ combined Haemophilus influenzae type b - meningococcal serogroup vaccine, Hib-MenC, Menitorix™

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Three doses of the vaccine were administered, in the lower left thigh at 2,4 and 6 months of age.

Prevenar™ + Menitorix™ Group

Arm description

The Group is also referred to as the Prevenar Group and included Subjects were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of Wyeth’s 7-valent pneumococcal conjugate vaccine (Prevenar™ or 7Pn) co-administered with Infanrix™ penta and Menitorix™, GSK Biologicals’ combined Hib-MenC vaccine (also referred to as HibMenC). All vaccines were administered intramuscularly (IM), Prevenar™ in the right thigh, Infanrix™ penta in the upper left thigh and Menitorix™, in the lower left thigh.

Arm type

Active comparator

Investigational medicinal product name

Prevenar

Investigational medicinal product code

Other name

Wyeth Lederle's 7-valent pneumococcal conjugate vaccine, 7Pn, Prevenar™

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Three doses of the vaccine were administered intramuscularly, in the lower left thigh at 2, 4 and 6 months of age.

Investigational medicinal product name

Infanrix penta

Investigational medicinal product code

Other name

DTPa-HBV-IPV, Infanrix™ penta

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Menitorix

Investigational medicinal product code

Other name

GSK Biologicals’ combined Haemophilus influenzae type b - meningococcal serogroup vaccine, Hib-MenC, Menitorix™

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Three doses of the vaccine were administered, in the lower left thigh at 2,4 and 6 months of age.

Number of subjects in period 1	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Started	391	393	392	396
Completed	376	374	373	376
Not completed	15	19	19	20
Adverse event, serious fatal	-	1	1	-
Consent withdrawn by subject	1	1	-	1
Adverse event, non-fatal	1	-	-	-
Other: protocol compliance issues	6	6	6	6
Migrated/moved from study area	-	-	-	1
Lost to follow-up	3	6	2	3
Protocol deviation	4	5	10	9

Baseline characteristics

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Reporting group title

GSK 1024850A + Meningitec™ Group

Reporting group description

Reporting group title

GSK 1024850A + NeisVac-C™ Group

Reporting group description

Subjects were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). In addition, subjects also received Baxter’s Men-C conjugate vaccine (NeisVac-C™, also referred to as Neis vaccine) at 2 and 4 months of age. For subjects in Poland and to comply with national recommendations, subjects were also offered a third dose of NeisVac-C™, at approximately 7 months of age, after the blood sampling performed at that time point. All vaccines were administered intramuscularly (IM), 10Pn in the right thigh, Infanrix™ hexa in the upper left thigh and NeisVac-C™, in the lower left thigh.

Reporting group title

GSK 1024850A + Menitorix™ Group

Reporting group description

Reporting group title

Prevenar™ + Menitorix™ Group

Reporting group description

Reporting group values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group	Total
Number of subjects	391	393	392	396	1572
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age continuous
Units: weeks
arithmetic mean (standard deviation)	8.3 ( 2.36 )	8.4 ( 2.31 )	8.4 ( 2.36 )	8.4 ( 2.38 )	-
Gender categorical
Units: Subjects
Female	192	187	216	187	782
Male	199	206	176	209	790

End points

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Reporting group title

GSK 1024850A + Meningitec™ Group

Reporting group description

Reporting group title

GSK 1024850A + NeisVac-C™ Group

Reporting group description

Subjects were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). In addition, subjects also received Baxter’s Men-C conjugate vaccine (NeisVac-C™, also referred to as Neis vaccine) at 2 and 4 months of age. For subjects in Poland and to comply with national recommendations, subjects were also offered a third dose of NeisVac-C™, at approximately 7 months of age, after the blood sampling performed at that time point. All vaccines were administered intramuscularly (IM), 10Pn in the right thigh, Infanrix™ hexa in the upper left thigh and NeisVac-C™, in the lower left thigh.

Reporting group title

GSK 1024850A + Menitorix™ Group

Reporting group description

Reporting group title

Prevenar™ + Menitorix™ Group

Reporting group description

Primary: Number of subjects reporting fever above (>) 39.0 degree Celsius (°C)

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End point title

Number of subjects reporting fever above (>) 39.0 degree Celsius (°C) ^[1]

End point description

Fever was measured as rectal temperature. Assessment of occurrences of fever > 39.0 °C was performed post doses1, 2 and 3 of 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines). This endpoint concerns subjects with at least one vaccination dose documented at the exclusion of the 24 subjects from a center located in Germany (6 in each group) were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit.

End point type

Primary

End point timeframe

Within 4 days (Day 0-3) after each vaccination and across all doses

Notes
[1] - 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: Inferential analysis was only applicable and applied to the GSK 1024850A + Menitorix™ and Prevenar™ + Menitorix™ groups

End point values	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	381	386
Units: Subjects
Post Dose 1 (N=381;386)	9	4
Post Dose 2 (N=379;385)	11	11
Post Dose 3 (N=370;375)	9	11
Across doses (N=381;386)	23	24

Non-inferiority of 10Pn vs 7Pn – Post Dose 1

Comparison groups

GSK 1024850A + Menitorix™ Group v Prevenar™ + Menitorix™ Group

Number of subjects included in analysis

767

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Difference in percentage

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

3.51

Notes
[2] - Analysis assessed the difference in percentage of subjects reporting fever >39.0°C. Non-inferiority was demonstrated if the upper limit of the standardized asymptotic 95% confidence interval of the difference (GSK 1024850A + Menitorix™ Group minus Prevenar™ + Menitorix™ Group), in terms of percentage of subjects with rectal fever >39.0°C, was lower than 10%.

Non-inferiority of 10Pn vs 7Pn – Post Dose 2

Comparison groups

GSK 1024850A + Menitorix™ Group v Prevenar™ + Menitorix™ Group

Number of subjects included in analysis

767

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Difference in percentage

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-2.45

upper limit

2.6

Notes
[3] - Analysis assessed the difference in percentage of subjects reporting fever >39.0°C. Non-inferiority was demonstrated if the upper limit of the standardized asymptotic 95% confidence interval of the difference (GSK 1024850A + Menitorix™ Group minus Prevenar™ + Menitorix™ Group), in terms of percentage of subjects with rectal fever >39.0°C, was lower than 10%.

Non-inferiority of 10Pn vs 7Pn – Post Dose 3

Comparison groups

GSK 1024850A + Menitorix™ Group v Prevenar™ + Menitorix™ Group

Number of subjects included in analysis

767

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Difference in percentage

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.04

upper limit

1.98

Notes
[4] - Analysis assessed the difference in percentage of subjects reporting fever >39.0°C. Non-inferiority was demonstrated if the upper limit of the standardized asymptotic 95% confidence interval of the difference (GSK 1024850A + Menitorix™ Group minus Prevenar™ + Menitorix™ Group), in terms of percentage of subjects with rectal fever >39.0°C, was lower than 10%.

Non-inferiority of 10Pn vs 7Pn – Across doses

Comparison groups

GSK 1024850A + Menitorix™ Group v Prevenar™ + Menitorix™ Group

Number of subjects included in analysis

767

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Difference in percentage

Point estimate

-0.18

Confidence interval

level

95%

sides

2-sided

lower limit

-3.68

upper limit

3.32

Notes
[5] - Analysis assessed the difference in percentage of subjects reporting fever >39.0°C. Non-inferiority was demonstrated if the upper limit of the standardized asymptotic 95% confidence interval of the difference (GSK 1024850A + Menitorix™ Group minus Prevenar™ + Menitorix™ Group), in terms of percentage of subjects with rectal fever >39.0°C, was 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 (G3) pain was defined as crying when limb was moved/spontaneously painful. G3 swelling/redness was defined as swelling/redness larger than (>) 30 millimeters (mm). “Any” is defined as incidence of the specified symptom regardless of intensity. This endpoint concerns subjects with at least one vaccination dose documented and with results available. The 24 subjects from a center located in Germany (6 in each group) who were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit were not taken into account in this analysis.

End point type

Secondary

End point timeframe

Within 4 days (Day 0-3) after each vaccination and across all doses

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	381	380	381	386
Units: Subjects
Any Pain, Post Dose 1 (N=380;380;381;386)	157	157	146	120
G3 Pain, Post Dose 1 (N=380;380;381;386)	20	15	18	11
Any Redness, Post Dose 1 (N=380;380;381;386)	172	172	171	155
G3 Redness, Post Dose 1 (N=380;380;381;386)	9	4	4	3
Any Swelling, Post Dose 1 (N=380;380;381;386)	143	120	133	108
G3 Swelling, Post Dose 1 (N=380;380;381;386)	16	7	5	4
Any Pain, Post Dose 2 (N=377;376;379;385)	131	119	128	121
G3 Pain, Post Dose 2 (N=377;376;379;385)	11	13	11	9
Any Redness, Post Dose 2 (N=377;376;379;385)	180	164	178	164
G3 Redness, Post Dose 2 (N=377;376;379;385)	8	7	5	5
Any Swelling, Post Dose 2 (N=377;376;379;385)	143	122	132	113
G3 Swelling, Post Dose 2 (N=377;376;379;385)	11	9	5	6
Any Pain, Post Dose 3 (N=373;373;370;375)	100	110	123	100
G3 Pain, Post Dose 3 (N=373;373;370;375)	4	2	5	3
Any Redness, Post Dose 3 (N=373;373;370;375)	177	164	169	172
G3 Redness, Post Dose 3 (N=373;373;370;375)	11	6	3	8
Any Swelling, Post Dose 3 (N=373;373;370;375)	137	124	143	137
G3 Swelling, Post Dose 3 (N=373;373;370;375)	8	6	4	9
Any Pain, Across Doses (N=381;380;381;386)	213	208	212	185
G3 Pain, Across Doses (N=381;380;381;386)	28	26	28	20
Any Redness, Across Doses (N=381;380;381;386)	255	236	242	239
G3 Redness, Across Doses (N=381;380;381;386)	21	16	9	12
Any Swelling, Across Doses (N=381;380;381;386)	216	189	207	190
G3 Swelling, Across Doses (N=381;380;381;386)	28	20	12	17

No statistical analyses for this end point

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

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End point title

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

End point description

Solicited general symptoms assessed include drowsiness (Drows), fever, irritability (Irr), and loss of appetite (Loss App). Grade 3 (G3) Drows was defined as drowsiness which prevented normal everyday activities. G3 fever was defined as fever (rectal temperature) above (>) 39.0 degree Celsius (°C). G3 Irr was defined as crying that could not be comforted/preventing normal everyday activities. G3 Loss App 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. This endpoint concerns subjects with at least one vaccination dose documented and with results available. The 24 subjects from a center located in Germany (6 in each group) who were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit were not taken into account in this analysis.

End point type

Secondary

End point timeframe

Within 4 days (Day 0-3) after each vaccination dose (D) and across all doses (AD)

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	381	380	381	386
Units: Subjects
Any Drows, Post D1 (N=381;380;381;386)	211	218	199	156
G3 Drows, Post D1 (N=381;380;381;386)	8	9	7	5
Any Fever, Post D1 (N=381;380;381;386)	166	192	141	95
G3 Fever, Post D1 (N=381;380;381;386)	12	15	9	4
Any Irr , Post D1 (N=381;380;381;386)	230	241	223	194
G3 Irr, Post D1 (N=381;380;381;386)	27	16	18	15
Any Loss App, Post D1 (N=381;380;381;386)	126	128	134	98
G3 Loss App, Post D1 (N=381;380;381;386)	6	3	1	1
Any Drows, Post D2 (N=377;376;379;385)	168	174	176	161
G3 Drows, Post D2 (N=377;376;379;385)	4	6	2	5
Any Fever, Post D2 (N=377;376;379;385)	169	156	138	142
G3 Fever, Post D2 (N=377;376;379;385)	15	17	11	11
Any Irr , Post D2 (N=377;376;379;385)	215	197	217	193
G3 Irr, Post D2 (N=377;376;379;385)	18	16	20	12
Any Loss App, Post D2 (N=377;376;379;385)	118	112	111	120
G3 Loss App, Post D2 (N=377;376;379;385)	1	2	0	2
Any Drows, Post D3 (N=373;373;370;375)	115	126	117	107
G3 Drows, Post D3 (N=373;373;370;375)	2	2	1	3
Any Fever, Post D3 (N=373;373;370;375)	90	87	90	89
G3 Fever, Post D3 (N=373;373;370;375)	14	12	9	11
Any Irr , Post D3 (N=373;373;370;375)	162	150	158	138
G3 Irr, Post D3 (N=373;373;370;375)	9	13	3	7
Any Loss App, Post D3 (N=373;373;370;375)	95	83	89	96
G3 Loss App, Post D3 (N=373;373;370;375)	1	3	1	2
Any Drows, AD (N=381;380;381;386)	268	276	265	252
G3 Drows, AD (N=381;380;381;386)	13	15	10	13
Any Fever, AD (N=381;380;381;386)	247	258	223	218
G3 Fever, AD (N=381;380;381;386)	36	40	23	24
Any Irr , AD (N=381;380;381;386)	301	294	293	281
G3 Irr, AD (N=381;380;381;386)	49	40	38	31
Any Loss App, AD (N=381;380;381;386)	203	200	209	196
G3 Loss App, AD (N=381;380;381;386)	8	7	2	4

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. This endpoint concerns subjects with at least one vaccination dose documented. The 24 subjects from a center located in Germany (6 in each group) who were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit were not taken into account in this analysis.

End point type

Secondary

End point timeframe

Within 31 days (Day 0-30) after each vaccination, across doses

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	385	387	386	390
Units: Subjects
Any unsolicited AE(s)	144	142	144	153

No statistical analyses for this end point

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

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End point title

Number of subjects with serious adverse events (SAEs) in vaccinated subjects

End point description

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. “Any” is defined an incidence of a SAE regardless of intensity/severity. This endpoint concerns subjects with at least one vaccination dose documented at the exclusion of the 24 subjects from a center located in Germany (6 in each group) were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit.

End point type

Secondary

End point timeframe

Throughout the Active Phase of the study, from first vaccination at 6-16 weeks of age till approximately 7 months of age.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	385	387	386	390
Units: Subjects
Any SAE(s)	8	14	10	13

No statistical analyses for this end point

Secondary: Number of subjects with serious adverse events (SAEs) in enrolled subjects who were eliminated from the study efficacy analyses

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End point title

Number of subjects with serious adverse events (SAEs) in enrolled subjects who were eliminated from the study efficacy analyses

End point description

End point type

Secondary

End point timeframe

Throughout the Active Phase of the study, from first vaccination at 6-16 weeks of age till approximately 7 months of age.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	6	6	6	6
Units: Subjects
Any SAE(s)	0	1	0	0

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

An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or may evolve into one of the outcomes listed above. “Any” is defined an incidence of a SAE regardless of intensity/severity. This endpoint concerns all subjects enrolled in the study, that is, eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) and the 24 subjects from a center located in Germany (6 in each group) who were later eliminated from analyses due to protocol compliance following findings of a for cause audit.

End point type

Secondary

End point timeframe

Throughout the entire study, from 1st vaccination at 6-16 weeks of age till the end of the ESFU Phase, when subjects reached approximately 12 months of age.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	391	393	392	396
Units: Subjects
Any SAE(s)	24	30	30	28

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 above or equal to (>=-) 0.20 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 above or equal to (>=-) 0.20 microgram per liter (µg/mL)

End point description

The number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) above or equal to >= 0.20 µg/mL was tabulated. The seroprotection and seropositivity cut-off values for the assay were >= 0.20 µg/mL and >= 0.05 µg/mL, respectively. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

At Month 5 (M5), aka one month after the administration of the third dose of the primary vaccination course with 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	169	175	173	170
Units: Subjects
Anti 1, at M5 (N=169;174;173;170)	163	170	161	1
Anti 4, at M5 (N=169;174;173;170)	169	173	170	170
Anti-5, at M5 (N=169;174;173;168)	169	174	171	4
Anti 6B, at M5 (N=169;175;173;169)	159	155	151	157
Anti 7F, at M5 (N=169;175;173;169)	169	174	171	5
Anti 9V, at M5 (N=169;175;173;169)	167	171	170	167
Anti 14, at M5 (N=169;175;173;169)	169	175	173	168
Anti 18C, at M5 (N=169;175;173;169)	167	173	172	167
Anti 19F, at M5 (N=169;175;173;170)	166	174	171	170
Anti 23F, at M5 (N=169;175;173;169)	162	168	160	159

No statistical analyses for this end point

Secondary: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations

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End point title

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations

End point description

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean concentrations (GMCs) and tabulated. The seropositivity cut-off for the assay was >= 0.05 microgram per millilitre (µg/mL). Antibody concentrations or titres < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	169	175	173	170
Units: µg/mL
geometric mean (confidence interval 95%)
Anti 1, at M5 (N=169;174;173;170)	1.17 (1.03 to 1.33)	1.09 (0.96 to 1.24)	1 (0.86 to 1.15)	0.03 (0.03 to 0.03)
Anti 4, at M5 (N=169;174;173;170)	1.88 (1.7 to 2.09)	1.96 (1.76 to 2.19)	1.7 (1.52 to 1.92)	2.78 (2.46 to 3.14)
Anti-5, at M5 (N=169;174;173;168)	1.96 (1.78 to 2.17)	1.87 (1.69 to 2.08)	1.69 (1.49 to 1.91)	0.03 (0.03 to 0.04)
Anti 6B, at M5 (N=169;175;173;169)	0.96 (0.82 to 1.12)	0.85 (0.72 to 1.01)	0.71 (0.59 to 0.86)	1.32 (1.12 to 1.57)
Anti 7F, at M5 (N=169;175;173;169)	2.82 (2.54 to 3.14)	2.57 (2.32 to 2.86)	2.25 (1.98 to 2.55)	0.04 (0.03 to 0.04)
Anti 9V, at M5 (N=169;175;173;169)	1.77 (1.58 to 2)	1.72 (1.52 to 1.95)	1.58 (1.4 to 1.77)	3.17 (2.75 to 3.64)
Anti 14, at M5 (N=169;175;173;169)	3.75 (3.25 to 4.31)	3.79 (3.37 to 4.26)	3.36 (2.91 to 3.88)	5.97 (5.05 to 7.07)
Anti 18C, at M5 (N=169;175;173;169)	2.43 (2.07 to 2.84)	3.92 (3.38 to 4.54)	2.34 (2.01 to 2.71)	3.01 (2.65 to 3.42)
Anti 19F, at M5 (N=169;175;173;170)	4.93 (4.28 to 5.68)	4.71 (4.09 to 5.42)	3.81 (3.32 to 4.37)	2.56 (2.29 to 2.86)
Anti 23F, at M5 (N=169;175;173;169)	1.3 (1.13 to 1.49)	1.2 (1.02 to 1.4)	0.96 (0.82 to 1.13)	2.46 (2.04 to 2.98)

No statistical analyses for this end point

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

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End point title

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

End point description

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (OPA Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was >= 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	162	168	161	156
Units: Titers
geometric mean (confidence interval 95%)
OPA Anti-1, at M5 (N=162;168;161;156)	23.9 (17.9 to 32)	18.8 (14.4 to 24.4)	19.7 (14.9 to 26.1)	4.2 (3.9 to 4.5)
OPA Anti-4, at M5 (N=154;159;159;154)	697.4 (617.8 to 787.3)	755.6 (660.9 to 863.7)	669.8 (553.8 to 810)	926.2 (779.5 to 1100.4)
OPA Anti-5, at M5 (N=153;163;159;153)	91.7 (72.7 to 115.7)	71.4 (56.5 to 90.4)	77.4 (61 to 98.2)	4.2 (4 to 4.5)
OPA Anti-6B, at M5 (N=148;150;148;151)	459.1 (334.2 to 630.8)	404.6 (287.7 to 569.1)	354.2 (243.4 to 515.3)	1575.3 (1230.8 to 2016)
OPA Anti-7F, at M5 (N=149;164;158;138)	2513.3 (2106.1 to 2999.3)	2821.3 (2297.9 to 3463.9)	2290.5 (1802.3 to 2910.9)	8.7 (6.3 to 11.9)
OPA Anti-9V, at M5 (N=153;153;155;150)	1005.6 (825.3 to 1225.2)	1108.8 (905.9 to 1357.1)	1122.6 (938.9 to 1342.3)	1305 (1046.3 to 1627.6)
OPA Anti-14, at M5 (N=154;167;160;154)	797.8 (655.3 to 971.2)	879 (709.1 to 1089.5)	779.9 (628.1 to 968.3)	1539.4 (1230.2 to 1926.2)
OPA Anti-18C, at M5 (N=155;163;157;149)	174.9 (144.1 to 212.3)	282.8 (234.7 to 340.8)	142.7 (113.8 to 179.1)	212.8 (174.9 to 258.9)
OPA Anti-19F, at M5 (N=157;165;159;147)	387.5 (305 to 492.2)	298.4 (230.3 to 386.7)	261 (200.9 to 339)	52 (40.8 to 66.4)
OPA Anti-23F, at M5 (N=146;156;146;148)	1066 (811.9 to 1399.6)	1219.6 (930.7 to 1598.2)	880.7 (633.1 to 1225.1)	5469.2 (4410.2 to 6782.6)

No statistical analyses for this end point

Secondary: Antibody concentrations to protein D (Anti-PD)

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End point title

Antibody concentrations to protein D (Anti-PD)

End point description

Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was >= 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	168	174	173	163
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD, at M5	2114 (1847.6 to 2418.8)	1715.5 (1494.9 to 1968.7)	1726.7 (1493.3 to 1996.7)	72.3 (64.5 to 81.1)

No statistical analyses for this end point

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

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End point title

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

End point description

Anti-PT, Anti-FHA and Anti-PRN concentrations measured by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was >= 5 EL.U/mL. Antibody concentrations < 5 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	168	174	173	168
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PT, at M5 (N=168;174;172;166)	38.4 (34.9 to 42.4)	43.1 (39.1 to 47.5)	42.2 (38.3 to 46.6)	43.2 (39.6 to 47.1)
Anti-FHA, at M5 (N=168;174;173;168)	162.6 (147.1 to 179.7)	184.3 (165.8 to 204.9)	189.2 (172.8 to 207.3)	191.2 (174 to 210.2)
Anti-PRN, at M5 (N=168;174:173;168)	95.1 (84.4 to 107.2)	107.5 (94 to 123)	99.9 (87.4 to 114.2)	110.5 (97.5 to 125.1)

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

Anti-D and Anti-TT antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in International units per milliliter (IU/mL), and tabulated. The seropositivity cut-off for the assay was >= 0.1 IU/mL. Antibody concentrations < 0.1 IU/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	169	175	173	169
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-D, at M5	2.808 (2.521 to 3.127)	2.263 (1.975 to 2.593)	2.436 (2.137 to 2.778)	2.615 (2.316 to 2.952)
Anti-TT, at M5	3.522 (3.185 to 3.896)	5.259 (4.828 to 5.729)	4.508 (4.134 to 4.916)	3.566 (3.265 to 3.895)

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

Anti-PRP antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (µg/mL), and tabulated. The seroprotection cut-off for the assay for the purpose of this endpoint was >= 0.15 µg/mL. Antibody concentrations < 0.15 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

At Month 4 (M4), aka 2 months after the administration of the 2nd dose of the primary vaccination course with 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	171	178	174	172
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP, at M4	1.429 (1.124 to 1.816)	2.704 (2.212 to 3.306)	1.99 (1.575 to 2.514)	1.591 (1.249 to 2.026)

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

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	168	174	172	170
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP, at M5	4.343 (3.556 to 5.304)	6.708 (5.762 to 7.81)	13.746 (11.406 to 16.567)	10.947 (9.165 to 13.077)

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

Anti-HBs antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in milli-International unit per milliliter (IU/mL), and tabulated per country (Germany, Poland, Spain) and in total – across all countries. The seropositivity cut-off for the assay was >= 10 mIU/mL. Antibody concentrations < 10 mIU/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	62	80	89	64
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs, In Germany, at M5 (N=12;17;16;9)	516 (289 to 921.2)	550.2 (246.4 to 1228.6)	533.9 (222.3 to 1282.2)	464.9 (262 to 825.1)
Anti-HBs, In Poland, at M5 (N=24;34;41;25)	1100.7 (819.9 to 1477.7)	1037.1 (868.4 to 1238.7)	925.4 (662.6 to 1292.3)	739.9 (542.3 to 1009.7)
Anti-HBs, In Spain, at M5 (N=26;29;32;30)	863.5 (609.8 to 1222.8)	684 (384.2 to 1218)	913.1 (655.4 to 1272)	908 (664.4 to 1241)
Anti-HBs, In Total, at M5 (N=62;80;89;64)	858.6 (692.9 to 1063.9)	779.5 (594.3 to 1022.4)	834.2 (655.4 to 1061.8)	762.9 (622.9 to 934.4)

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

Anti-Polio 1, 2 and 3 antibody titers were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seroprotection cut-off for the assay was >= 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	39	44	49	41
Units: Titers
geometric mean (confidence interval 95%)
Anti-Polio 1, at M5 (N=39;44;49;41)	284.9 (191.6 to 423.6)	427.2 (301.1 to 606.3)	454.2 (319.6 to 645.4)	371.3 (247 to 558.1)
Anti-Polio 2, at M5 (N=31;42;46;32)	327.1 (196.7 to 543.9)	251.8 (176.2 to 359.9)	263.8 (170.8 to 407.6)	298.2 (184.8 to 481.3)
Anti-Polio 3, at M5 (N=34;36;49;38)	572.8 (361.7 to 907.3)	608.9 (413.6 to 896.5)	590 (402.7 to 864.5)	666.5 (410.6 to 1081.7)

No statistical analyses for this end point

Secondary: Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 micrograms per milliiter (µg/mL)

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End point title

Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 micrograms per milliiter (µg/mL)

End point description

The number of subjects with Anti-PSC above or equal to >= 2.0 µg/mL was tabulated. The seroprotection and seropositivity cut-off values for the assay were >= 2.0 µg/mL and >= 0.30 µg/mL, respectively. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

At Month 4 (M4), aka 2 months after the administration of the 2nd dose of the primary vaccination course with 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	170	178	174	171
Units: Subjects
Anti PSC >=2.0 µg/mL, at M4 (N=170;178;174;171)	163	172	159	154

No statistical analyses for this end point

Secondary: Anti-polysaccharide C (Anti-PSC) antibody concentrations

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End point title

Anti-polysaccharide C (Anti-PSC) antibody concentrations

End point description

Anti-PSC antibody concentrations were calculated, expressed as geometric mean concentrations (GMCs), in microgram per milliliter (µg/mL), and tabulated. The seropositivity cut-off for the assay was >= 0.30 µg/mL. Antibody concentrations < 0.30 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Seroprotection status, defined as: Anti-PRP antibody concentrations ≥ 0.15 and ≥ 1.0 µg/mL. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

At Month 4 (M4), aka 2 months after the administration of the 2nd dose of the primary vaccination course with 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	170	178	174	171
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PSC, at M4 (N=170;178;174;171)	5.96 (5.42 to 6.57)	7.99 (7.28 to 8.77)	6.1 (5.47 to 6.8)	5.64 (5.05 to 6.3)

No statistical analyses for this end point

Secondary: Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 microgram per milliiter (µg/mL)

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End point title

Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 microgram per milliiter (µg/mL)

End point description

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	168	174	173	169
Units: Subjects
Anti-PSC >=2.0 µg/mL, at M5 (N=168;174;173;169)	138	160	166	161

No statistical analyses for this end point

Secondary: Anti-polysaccharide C (Anti-PSC) antibody concentrations

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End point title

Anti-polysaccharide C (Anti-PSC) antibody concentrations

End point description

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	168	174	173	169
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PSC, at M5 (N=168;174;173;169)	4.08 (3.64 to 4.56)	5.64 (5.13 to 6.2)	7.27 (6.59 to 8.01)	6.17 (5.58 to 6.81)

No statistical analyses for this end point

Secondary: Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

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End point title

Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

End point description

The number of subjects with rSBA-MenC) antibody titres above or equal to >= 128 was tabulated. The seroprotection cut-off value for the assay was >= 8. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

At Month 4 (M4), aka 2 months after the administration of the 2nd dose of the primary vaccination course with 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	165	177	168	166
Units: Subjects
rSBA-MenC>=128, at M4 (N=165;177;168;166)	160	172	150	146

No statistical analyses for this end point

Secondary: Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

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End point title

Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

End point description

rSBA-MenC antibody titres were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seroprotection cut-off value for the assay was >= 8. Analysis for this endpoint was performed on eligible subjects with at least one vaccination dose documented (please refer to endpoint “Number of subjects with serious adverse events (SAEs) in vaccinated subjects” for a description of these subjects) for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.

End point type

Secondary

End point timeframe

At Month 4 (M4), aka 2 months after the administration of the 2nd dose of the primary vaccination course with 10Pn-PD-DiT or 7Pn vaccine co-administered with DTPa-combined, MenC or Hib-MenC vaccines.

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	165	177	168	166
Units: Titers
geometric mean (confidence interval 95%)
rSBA-MenC, at M4 (N=165;177;168;166)	1299.8 (1082 to 1561.5)	1474.2 (1263.3 to 1720.4)	501.8 (410.3 to 613.6)	480.4 (399.1 to 578.2)

No statistical analyses for this end point

Secondary: Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

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End point title

Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

End point description

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	126	138	137	120
Units: Subjects
rSBA-MenC>=128, at M5 (N=126;138;137;120)	118	134	133	114

No statistical analyses for this end point

Secondary: Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

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End point title

Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

End point description

End point type

Secondary

End point timeframe

End point values	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Number of subjects analysed	126	138	137	120
Units: Titers
geometric mean (confidence interval 95%)
rSBA-MenC, at M5 (N=126;138;137;120)	665.2 (528.8 to 836.8)	1152.6 (958.4 to 1386.3)	1590.9 (1298.5 to 1949.1)	1207.7 (964.4 to 1512.3)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms and unsolicited AEs: within 4 and 31 days post vaccination, across doses, respectively. SAEs: Between Dose 1 at 6-16 weeks of age till the end of the ESFU Phase, when subjects reached approximately 12 months of age.

Adverse event reporting additional description

Occurrences of reported AEs (all/related) were not available and are encoded as equal to the number of subjects affected. Note that safety events reported below include the SAEs reported for the 24 subjects from a center located in Germany (6 in each group) who were excluded from efficacy analyses due to protocol compliance issues.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

11.0

Reporting group title

GSK 1024850A + Meningitec™ Group

Reporting group description

Reporting group title

GSK 1024850A + NeisVac-C™ Group

Reporting group description

Subjects were vaccinated with a 3-dose course administered at 2, 4 and 6 months of age of GSK Biologicals’ pneumococcal conjugate vaccine GSK1024850A (also referred to as 10Pn-PD-DiT or 10Pn vaccine) co-administered with Infanrix™ hexa (also referred to as DTPa-HBV-IPV/Hib). In addition, subjects also received Baxter’s Men-C conjugate vaccine (NeisVac-C™, also referred to as Neis vaccine) at 2 and 4 months of age. For subjects in Poland and to comply with national recommendations, subjects were also offered a third dose of NeisVac-C™, at approximately 7 months of age, after the blood sampling performed at that time point. All vaccines were administered intramuscularly (IM), 10Pn in the right thigh, Infanrix™ hexa in the upper left thigh and NeisVac-C™, in the lower left thigh.

Reporting group title

GSK 1024850A + Menitorix™ Group

Reporting group description

Reporting group title

Prevenar™ + Menitorix™ Group

Reporting group description

Serious adverse events	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Total subjects affected by serious adverse events
subjects affected / exposed	24 / 391 (6.14%)	30 / 393 (7.63%)	30 / 392 (7.65%)	28 / 396 (7.07%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	1 / 392 (0.26%)	2 / 396 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Reproductive system and breast disorders
Genital labial adhesions
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
subjects affected / exposed	3 / 391 (0.77%)	3 / 393 (0.76%)	1 / 392 (0.26%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Apnoea
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	1 / 396 (0.25%)
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
Allergic bronchitis
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Wheezing
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
Injury, poisoning and procedural complications
Fracture
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	1 / 396 (0.25%)
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
Contusion
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Iron deficiency anaemia
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Diarrhoea
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	3 / 396 (0.76%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroesophageal reflux disease
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Dyspepsia
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Enteritis
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Gastritis
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Hepatobiliary disorders
Hepatosplenomegaly
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Urticaria
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Rash
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Renal and urinary disorders
Cystitis noninfective
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
Musculoskeletal and connective tissue disorders
Rickets
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	3 / 391 (0.77%)	2 / 393 (0.51%)	2 / 392 (0.51%)	1 / 396 (0.25%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	3 / 391 (0.77%)	6 / 393 (1.53%)	1 / 392 (0.26%)	3 / 396 (0.76%)
occurrences causally related to treatment / all	0 / 3	0 / 6	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 391 (0.00%)	4 / 393 (1.02%)	2 / 392 (0.51%)	1 / 396 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	2 / 391 (0.51%)	2 / 393 (0.51%)	3 / 392 (0.77%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 391 (0.51%)	3 / 393 (0.76%)	8 / 392 (2.04%)	5 / 396 (1.26%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 8	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	4 / 391 (1.02%)	1 / 393 (0.25%)	4 / 392 (1.02%)	3 / 396 (0.76%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 391 (0.00%)	2 / 393 (0.51%)	1 / 392 (0.26%)	1 / 396 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess of eyelid
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis salmonella
subjects affected / exposed	1 / 391 (0.26%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
Pharyngitis
subjects affected / exposed	0 / 391 (0.00%)	3 / 393 (0.76%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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
Pneumococcal sepsis
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
Pyelonephritis acute
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	1 / 392 (0.26%)	0 / 396 (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 syncytial virus bronchiolitis
subjects affected / exposed	1 / 391 (0.26%)	1 / 393 (0.25%)	1 / 392 (0.26%)	1 / 396 (0.25%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 391 (0.00%)	2 / 393 (0.51%)	1 / 392 (0.26%)	3 / 396 (0.76%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	0 / 391 (0.00%)	3 / 393 (0.76%)	1 / 392 (0.26%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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
Infectious mononucleosis
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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
Influenza
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
Kawasaki’s disease
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Laryngitis
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Measles
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	0 / 392 (0.00%)	0 / 396 (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
Meningitis viral
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Otitis media
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	0 / 392 (0.00%)	1 / 396 (0.25%)
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
Pseudocroup
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	0 / 396 (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
Respiratory tract infection
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Upper respiratory tract infection
subjects affected / exposed	0 / 391 (0.00%)	1 / 393 (0.25%)	1 / 392 (0.26%)	0 / 396 (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
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 391 (0.00%)	0 / 393 (0.00%)	1 / 392 (0.26%)	2 / 396 (0.51%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Amino acid metabolism disorder
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Hyponatraemia
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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
Vitamin b complex deficiency
subjects affected / exposed	1 / 391 (0.26%)	0 / 393 (0.00%)	0 / 392 (0.00%)	0 / 396 (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

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

Non-serious adverse events	GSK 1024850A + Meningitec™ Group	GSK 1024850A + NeisVac-C™ Group	GSK 1024850A + Menitorix™ Group	Prevenar™ + Menitorix™ Group
Total subjects affected by non serious adverse events
subjects affected / exposed	301 / 391 (76.98%)	294 / 393 (74.81%)	293 / 392 (74.74%)	281 / 396 (70.96%)
General disorders and administration site conditions
Pain
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	213 / 381 (55.91%)	208 / 380 (54.74%)	212 / 381 (55.64%)	185 / 386 (47.93%)
occurrences all number	213	208	212	185
Redness
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	255 / 381 (66.93%)	236 / 380 (62.11%)	242 / 381 (63.52%)	239 / 386 (61.92%)
occurrences all number	255	236	242	239
Swelling
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	216 / 381 (56.69%)	189 / 380 (49.74%)	207 / 381 (54.33%)	190 / 386 (49.22%)
occurrences all number	216	189	207	190
Drowsiness
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	268 / 381 (70.34%)	276 / 380 (72.63%)	265 / 381 (69.55%)	252 / 386 (65.28%)
occurrences all number	268	276	265	252
Fever >= 38.0°C
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	247 / 381 (64.83%)	258 / 380 (67.89%)	223 / 381 (58.53%)	218 / 386 (56.48%)
occurrences all number	247	258	223	218
Irritability
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	301 / 381 (79.00%)	294 / 380 (77.37%)	293 / 381 (76.90%)	281 / 386 (72.80%)
occurrences all number	301	294	293	281
Loss of appetite
alternative dictionary used: MedDRA 10.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	203 / 381 (53.28%)	200 / 380 (52.63%)	209 / 381 (54.86%)	196 / 386 (50.78%)
occurrences all number	203	200	209	196
Infections and infestations
Upper respiratory tract infection
alternative dictionary used: MedDRA 10.0
subjects affected / exposed ^[8]	30 / 385 (7.79%)	30 / 387 (7.75%)	28 / 386 (7.25%)	32 / 390 (8.21%)
occurrences all number	30	30	28	32

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Analysis for this Event was only performed on subjects for whom the specified symptom was reported.
[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: This event only concerns subjects with at least one vaccination dose documented at the exclusion of the 24 subjects from a center located in Germany (6 in each group) were later eliminated and excluded from efficacy analyses due to protocol compliance following findings of a for cause audit.

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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.

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 fever above (>) 39.0 degree Celsius (°C)

Primary: Number of subjects reporting fever above (>) 39.0 degree 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 and any Grade 3 solicited general symptoms

Secondary: Number of subjects with any and any Grade 3 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) in vaccinated subjects

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

Secondary: Number of subjects with serious adverse events (SAEs) in enrolled subjects who were eliminated from the study efficacy analyses

Secondary: Number of subjects with serious adverse events (SAEs) in enrolled subjects who were eliminated from the study efficacy analyses

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

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

Secondary: Number of subjects with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations above or equal to (>=-) 0.20 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 above or equal to (>=-) 0.20 microgram per liter (µg/mL)

Secondary: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations

Secondary: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations

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

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

Secondary: Antibody concentrations to protein D (Anti-PD)

Secondary: Antibody concentrations to protein D (Anti-PD)

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

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

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

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

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

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

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

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

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-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 micrograms per milliiter (µg/mL)

Secondary: Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 micrograms per milliiter (µg/mL)

Secondary: Anti-polysaccharide C (Anti-PSC) antibody concentrations

Secondary: Anti-polysaccharide C (Anti-PSC) antibody concentrations

Secondary: Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 microgram per milliiter (µg/mL)

Secondary: Number of subjects with anti-polysaccharide C (Anti-PSC) antibody concentrations >= 2.0 microgram per milliiter (µg/mL)

Secondary: Anti-polysaccharide C (Anti-PSC) antibody concentrations

Secondary: Anti-polysaccharide C (Anti-PSC) antibody concentrations

Secondary: Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

Secondary: Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

Secondary: Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

Secondary: Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

Secondary: Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

Secondary: Number of subjects with serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers >= 128

Secondary: Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

Secondary: Serum bactericidal assay (performed using baby rabbit complement) for Neisseria meningitidis serogroups C (rSBA-MenC) antibody titers

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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