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Clinical Trial Results:
A phase IIIb open, controlled study to evaluate the immunogenicity, safety and reactogenicity of GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine when given as a catch-up immunization in children older than 7 months of age or given as a 3-dose primary immunization in children before 6 months of age.

Summary
EudraCT number	2006-001482-42
Trial protocol	FI
Global end of trial date	15 Nov 2007

Results information
Results version number	v3(current)
This version publication date	09 Aug 2022
First version publication date	14 Jun 2015
Other versions	v1 , v2
Version creation reason	Correction of full data set Correction of full data set and alignment between registries.

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

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Trial information

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Sponsor protocol code

107058

ISRCTN number

US NCT number

NCT00345358

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

29 Apr 2008

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Nov 2007

Was the trial ended prematurely?

Main objective of the trial

To evaluate the immunogenicity of GSK Biologicals’ 10-valent pneumococcal conjugate vaccine, when given as a catch-up immunization in children older than 7 months of age (three age-groups with different schedules).

Protection of trial subjects

All vaccines were observed closely for at least 30 minutes following the administration of vaccines, with appropriate medical treatment readily available in case of a rare anaphylactic reaction. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were followed up for up to 31 days for adverse events after the last vaccination/product administration and during the entire study period for serious adverse events.

Background therapy

Evidence for comparator

Actual start date of recruitment

18 Sep 2006

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Finland: 600

Worldwide total number of subjects

600

EEA total number of subjects

600

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)

450

Children (2-11 years)

150

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 a primary (PRI) phase (all groups) and a booster (BST) phase [only 10Pn less than (<)6M and 10Pn 7-11M groups].

Screening details

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

Period 1 title

Primary Vaccination Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

10Pn <6M Group

Arm description

This group consisted of subjects up to 6 months of age at first vaccination who received 3 doses of 10Pn-PD-DiT (or 10Pn) vaccine co-administered with Infanrix IPV/Hib (DTPa-IPV/Hib) at 3, 4 and 5 months of age and a booster dose of the same vaccines at 12-15 months of age. Vaccines were administrated intramuscularly in the right (10Pn-PD-DiT) or the left (DTPa-IPV/Hib) thigh or deltoid region [deltoid region only for children greater than (>)12 months of age if muscle size was adequate].

Arm type

Experimental

Investigational medicinal product name

10-valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 primary doses administered at 3, 4 and 5 months of age followed by a booster dose at 12-15 months of age, all injected intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Investigational medicinal product name

DTPa-IPV/Hib

Investigational medicinal product code

Other name

Infanrix IPV/Hib, Infanrix-Polio+Hib

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 primary doses administered at 3, 4 and 5 months of age followed by a booster dose at 12-15 months of age, all injected intramuscularly in the left right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

10Pn 7-11M Group

Arm description

This group consisted of subjects 7 to 11 months of age at first vaccination who received 2 doses of 10Pn-PD-DiT (10Pn), one first dose at enrolment followed by a second dose one month later, and a booster dose at 12-15 months of age. The 10PN-PD-DiT vaccine was administrated intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Arm type

Experimental

Investigational medicinal product name

10-valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses, one first dose at enrolment followed by a second dose one month later, followed by a booster dose at 12-15 months of age, injected intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

10Pn 12-23M Group

Arm description

This group consisted of subjects 12 to 23 months inclusive at first vaccination who received 2 doses of 10Pn-PD-DiT (10Pn), one first dose at enrolment followed by a second dose 2 months later. The 10PN-PD-DiT vaccine was administrated intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Arm type

Experimental

Investigational medicinal product name

10-valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of 10Pn-PD-DiT (10Pn), one first dose at enrolment followed by a second dose 2 months later, injected intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

10Pn >=24M Group

Arm description

This group consisted of subjects aged between 24 months (inclusive) to 5 years (inclusive) at vaccination who received one dose of 10Pn-PD-DiT (10Pn). The 10PN-PD-DiT vaccine was administrated intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Arm type

Experimental

Investigational medicinal product name

10-valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

One dose administered when subject’s age was between 24 months (inclusive) to 5 years of age (inclusive) at vaccination, injected intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Number of subjects in period 1	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Started	150	150	150	150
Completed	145	146	142	148
Not completed	5	4	8	2
Consent withdrawn by subject	1	2	4	-
Adverse event, non-fatal	3	1	1	-
Other reason (unspecified)	-	1	1	-
Lost to follow-up	1	-	2	2

Period 2 title

Booster Vaccination Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

10Pn <6M Group

Arm description

This group consisted of subjects up to 6 months of age at first vaccination who received 3 doses of 10Pn-PD-DiT (or 10Pn) vaccine co-administered with Infanrix IPV/Hib (DTPa-IPV/Hib) at 3, 4 and 5 months of age and a booster dose of the same vaccines at 12-15 months of age. Vaccines were administrated intramuscularly in the right (10Pn-PD-DiT) or the left (DTPa-IPV/Hib) thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Arm type

Experimental

Investigational medicinal product name

10-valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

DTPa-IPV/Hib

Investigational medicinal product code

Other name

Infanrix IPV/Hib, Infanrix-Polio+Hib

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

10Pn 7-11M Group

Arm description

Arm type

Experimental

Investigational medicinal product name

10-valent streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

Other name

10Pn-PD-DiT, 10Pn

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses, one first dose at enrolment followed by a second dose one month later, followed by a booster dose at 12-15 months of age., injected intramuscularly in the right thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Number of subjects in period 2 ^[1]	10Pn <6M Group	10Pn 7-11M Group
Started	145	145
Completed	141	145
Not completed	4	0
Consent withdrawn by subject	1	-
Lost to follow-up	3	-

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: One subject from the 10Pn 7-11M Group was not included in the Booster Phase of the study for not having received the booster vaccination dose.

Baseline characteristics

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Reporting group title

10Pn <6M Group

Reporting group description

Reporting group title

10Pn 7-11M Group

Reporting group description

Reporting group title

10Pn 12-23M Group

Reporting group description

Reporting group title

10Pn >=24M Group

Reporting group description

Reporting group values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group	Total
Number of subjects	150	150	150	150	600
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: months
arithmetic mean (standard deviation)	10.8 ( 1.09 )	8.3 ( 1.2 )	17.9 ( 3.19 )	36.6 ( 11.87 )	-
Gender categorical
Units: Subjects
Female	66	68	76	72	282
Male	84	82	74	78	318

End points

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Reporting group title

10Pn <6M Group

Reporting group description

Reporting group title

10Pn 7-11M Group

Reporting group description

Reporting group title

10Pn 12-23M Group

Reporting group description

Reporting group title

10Pn >=24M Group

Reporting group description

Reporting group title

10Pn <6M Group

Reporting group description

This group consisted of subjects up to 6 months of age at first vaccination who received 3 doses of 10Pn-PD-DiT (or 10Pn) vaccine co-administered with Infanrix IPV/Hib (DTPa-IPV/Hib) at 3, 4 and 5 months of age and a booster dose of the same vaccines at 12-15 months of age. Vaccines were administrated intramuscularly in the right (10Pn-PD-DiT) or the left (DTPa-IPV/Hib) thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Reporting group title

10Pn 7-11M Group

Reporting group description

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

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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 greater than or equal to (>=)0.20 microgram per milliliter (µg/mL) (Primary/full vaccination) ^[1]

End point description

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition Enzyme-Linked Immuno-Sorbent Assay (ELISA) method. The >=0.20 microgram per milliliter (microg/mL) cut-off corresponded to the seroprotection cut-off as regards anti-pneumococcal serotypes antibody concentrations. Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >= 0.05 microg/mL. The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available. This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one blood sampling time point after primary vaccination.

End point type

Primary

End point timeframe

At one month after primary (10Pn <6M & 10Pn 7-11M groups) or after the full (10Pn 12-23M & 10Pn >=24M groups) vaccination course with 10Pn, that is Month (M)3 for 10Pn <6M & 12-23M groups, M2 for 10Pn 7-11M Group, & M1

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

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	131	135	133	140
Units: Subjects
Anti-1 (N=131; 135; 133; 140)	128	135	132	135
Anti-4 (N=131; 135; 133; 140)	128	135	133	140
Anti-5(N=131; 135; 133; 138)	130	134	131	135
Anti-6B (N=131; 135; 133; 140)	95	69	108	96
Anti-7F (N=131; 135; 133; 140)	130	135	133	140
Anti-9V (N=131; 135; 133; 140)	128	129	130	132
Anti-14 (N=131; 135; 133; 139)	130	132	132	127
Anti-18C (N=131; 135; 133; 140)	127	135	133	140
Anti-19F (N=130; 135; 133; 140)	122	129	131	140
Anti-23F (N=131; 135; 133; 139)	114	95	122	93

No statistical analyses for this end point

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

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End point title

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

End point description

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (ANTI-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Seropositivity = Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >=0.05 µg/mL. The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available. This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one blood sampling time point after primary vaccination.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary ( <6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with 10Pn-PD-DiT vaccine

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	131	135	133	140
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 (N=131; 135; 133; 140)	1.2 (1.02 to 1.42)	1.19 (1.05 to 1.35)	1.22 (1.06 to 1.4)	0.77 (0.66 to 0.89)
Anti-4 (N=131; 135; 133; 140)	1.84 (1.57 to 2.15)	3.47 (3.03 to 3.97)	4.21 (3.77 to 4.69)	5.72 (5 to 6.54)
Anti-5(N=131; 135; 133; 138)	2.04 (1.75 to 2.37)	1.72 (1.51 to 1.96)	1.8 (1.57 to 2.06)	1.16 (0.99 to 1.36)
Anti-6B (N=131; 135; 133; 140)	0.37 (0.29 to 0.48)	0.21 (0.16 to 0.26)	0.53 (0.43 to 0.65)	0.38 (0.3 to 0.47)
Anti-7F (N=131; 135; 133; 140)	2.03 (1.76 to 2.33)	2.1 (1.83 to 2.41)	3.62 (3.22 to 4.06)	2.6 (2.25 to 3.01)
Anti-9V (N=131; 135; 133; 140)	1.33 (1.14 to 1.55)	0.91 (0.78 to 1.07)	1.5 (1.3 to 1.73)	1.01 (0.84 to 1.22)
Anti-14 (N=131; 135; 133; 139)	3 (2.61 to 3.46)	2.3 (1.95 to 2.72)	4.24 (3.64 to 4.95)	1.36 (1.06 to 1.74)
Anti-18C (N=131; 135; 133; 140)	1.84 (1.5 to 2.26)	4.82 (4.14 to 5.61)	9.2 (8.22 to 10.29)	4.65 (4.06 to 5.31)
Anti-19F (N=130; 135; 133; 140)	1.61 (1.28 to 2.02)	3.36 (2.68 to 4.2)	5.45 (4.63 to 6.41)	5.26 (4.34 to 6.39)
Anti-23F (N=131; 135; 133; 139)	0.62 (0.5 to 0.76)	0.4 (0.32 to 0.5)	0.88 (0.73 to 1.05)	0.37 (0.3 to 0.47)

No statistical analyses for this end point

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

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End point title

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

End point description

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 6A, 19A (ANTI-6A, -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). Seropositivity = Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 µg/mL. The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available. This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one blood sampling time point after primary vaccination.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary ( <6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with 10Pn-PD-DiT vaccine

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	132	135	133	138
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A (N=132;135;133;138)	0.1 (0.08 to 0.12)	0.06 (0.05 to 0.08)	0.23 (0.18 to 0.29)	0.24 (0.19 to 0.31)
Anti-19A (N=131;135;133;138)	0.09 (0.07 to 0.11)	0.12 (0.1 to 0.15)	0.86 (0.71 to 1.05)	0.65 (0.53 to 0.82)

No statistical analyses for this end point

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

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End point title

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

End point description

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Seropositivity = Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available. This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one blood sampling time point after primary vaccination.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary ( <6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with 10Pn-PD-DiT vaccine

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	44	48	51	41
Units: Titer
geometric mean (confidence interval 95%)
Opsono-1 (N=44;48;51;41)	17.3 (10.9 to 27.5)	14.8 (9.3 to 23.6)	14.2 (9 to 22.4)	17.5 (9.4 to 32.3)
Opsono-4 (N=41;46;50;36)	675.6 (475.4 to 960)	524 (361.8 to 758.9)	912.1 (617.8 to 1346.8)	2227.6 (1694 to 2929.3)
Opsono-5(N=42;46;50;39)	52.6 (33.7 to 82.2)	33.7 (21.4 to 53.3)	47.5 (30.2 to 74.8)	14.1 (9.1 to 22)
Opsono-6B (N=38;45;49;34)	296 (130.3 to 672.2)	25.4 (11.1 to 58.4)	304.3 (143.8 to 644.2)	331.7 (99.1 to 1109.8)
Opsono-7F (N=43;46;48;38)	1775.1 (1057.8 to 2978.8)	2342.5 (1555.2 to 3528.2)	4164.2 (2840.4 to 6105)	3282.2 (2105.1 to 5117.6)
Opsono-9V (N=41;44;50;37)	1281.1 (895 to 1833.7)	2209.6 (1628.6 to 2997.8)	3525.8 (2675.4 to 4646.4)	4526 (3581.7 to 5719.3)
Opsono-14 (N=42;48;51;40)	1523.3 (1028.7 to 2255.6)	1818.9 (1356.4 to 2439.2)	2277.2 (1804.9 to 2873)	1957.4 (1516.6 to 2526.3)
Opsono-18C (N=41;46;51 ;38)	181.8 (120.8 to 273.5)	971.7 (723.2 to 1305.5)	1765.3 (1330.5 to 2342.2)	2051.4 (1558.3 to 2700.5)
Opsono-19F (N=42;43;50;41)	194.7 (101.7 to 372.7)	225.6 (128.6 to 395.7)	592.7 (367.3 to 956.4)	634.3 (400.2 to 1005.4)
Opsono-23F (N=41;45;49;41)	925.8 (422.6 to 2028.3)	561.1 (273.7 to 1150.4)	1656.4 (1063.6 to 2579.6)	1575.2 (802.6 to 3091.7)

No statistical analyses for this end point

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

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End point title

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

End point description

OPA titers against pneumococcal serotypes 6A, 19A (Opsono-6A, 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A >= 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available. This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one blood sampling time point after primary vaccination.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary ( <6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with 10Pn-PD-DiT vaccine

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	43	45	50	38
Units: Titer
geometric mean (confidence interval 95%)
Opsono-6A (N=41;44;50;35)	14.4 (7.5 to 27.6)	39.1 (19 to 80.6)	150.7 (80.7 to 281.3)	324.6 (142.6 to 738.6)
Opsono-19 (N=43;45;49;38)	5.1 (3.9 to 6.6)	6.1 (4.2 to 8.8)	39.5 (19 to 81.9)	31.8 (14.3 to 70.7)

No statistical analyses for this end point

Secondary: Antibody concentrations against protein D (anti-PD) (Primary/full vaccination)

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End point title

Antibody concentrations against protein D (anti-PD) (Primary/full vaccination)

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 milliliter (EL.U/mL) and tabulated. Seropositivity = Anti-PD antibody concentrations >= 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. The analysis was performed on the Primary According-To-Protocol cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available. This included subjects with assay results available for antibodies against at least one study vaccine antigen component and at least one blood sampling time point after primary vaccination.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary ( <6 months and 7-11 months groups) or the full (12-23 months and >= 24 months groups) vaccination course, with 10Pn-PD-DiT vaccine

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	131	135	133	139
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD [N=131;135;133;139]	1637.7 (1430.9 to 1874.3)	654.2 (577.7 to 741)	660 (554.9 to 785.1)	224.8 (185.2 to 272.7)

No statistical analyses for this end point

Secondary: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >= 0.20 µg/mL (Booster vaccination)

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End point title

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >= 0.20 µg/mL (Booster vaccination)

End point description

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition Enzyme-Linked Immuno-Sorbent Assay (ELISA) method. The >=0.20 microgram per millilitre (microg/mL) cut-off corresponded to the seroprotection cut-off as regards anti-pneumococcal serotypes antibody concentrations. Seropositivity = Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >=0.05 µg/mL. The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available (subjects from the 10Pn <6M & 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination).

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn for the < 6 months and 7-11 months groups

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	140	114
Units: Subjects
Anti-1, PRE(N=140;114)	101	102
Anti-1, POST(N=137;114)	137	114
Anti-4, PRE(N=140;114)	119	112
Anti-4, POST(N=137;114)	137	114
Anti-5, PRE(N=140;114)	123	110
Anti-5, POST(N=137;114)	136	114
Anti-6B, PRE(N=140;114)	108	97
Anti-6B, POST(N=137;114)	132	110
Anti-7F, PRE(N=140;114)	132	114
Anti-7F, POST(N=137;114)	137	114
Anti-9V, PRE(N=140;114)	131	108
Anti-9V, POST(N=137;114)	137	114
Anti-14, PRE(N=140;114)	131	113
Anti-14, POST(N=137;114)	137	114
Anti-18C, PRE(N=140;114)	127	114
Anti-18C, POST(N=137;114)	137	114
Anti-19F, PRE(N=140;114)	114	112
Anti-19F, POST(N=137;114)	134	112
Anti-23F, PRE(N=140;114)	116	98
Anti-23F, POST(N=137;114)	136	110

No statistical analyses for this end point

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

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End point title

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

End point description

Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were assessed by 22F-inhibition Enzyme-Linked Immuno-Sorbent Assay (ELISA) method. The >=0.20 microgram per millilitre (microg/mL) cut-off corresponded to the seroprotection cut-off as regards anti-pneumococcal serotypes antibody concentrations. Seropositivity status, defined as Anti-pneumococcal serotypes antibody concentrations >=0.05 µg/mL. The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available (subjects from the 10Pn <6M & 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination).

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn for the < 6 months and 7-11 months groups

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	140	141
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1, PRE(N=140;114)	0.29 (0.25 to 0.34)	0.49 (0.43 to 0.57)
Anti-1, POST(N=137;114)	1.84 (1.59 to 2.12)	1.77 (1.55 to 2.02)
Anti-4, PRE(N=140;114)	0.56 (0.48 to 0.66)	1.35 (1.17 to 1.57)
Anti-4, POST(N=137;114)	2.98 (2.6 to 3.42)	3.79 (3.27 to 4.4)
Anti-5, PRE(N=140;114)	0.51 (0.44 to 0.59)	0.8 (0.7 to 0.93)
Anti-5, POST(N=137;114)	2.21 (1.94 to 2.53)	2.88 (2.48 to 3.34)
Anti-6B, PRE(N=140;114)	0.41 (0.34 to 0.5)	0.48 (0.4 to 0.58)
Anti-6B, POST(N=137;114)	1.62 (1.35 to 1.94)	1.39 (1.14 to 1.69)
Anti-7F, PRE(N=140;114)	0.82 (0.72 to 0.94)	1.58 (1.39 to 1.8)
Anti-7F, POST(N=137;114)	3.31 (2.92 to 3.74)	3.73 (3.24 to 4.28)
Anti-9V, PRE(N=140;114)	0.85 (0.73 to 0.98)	0.79 (0.67 to 0.93)
Anti-9V, POST(N=137;114)	3.41 (2.96 to 3.92)	2.13 (1.82 to 2.5)
Anti-14, PRE(N=140;114)	1.03 (0.85 to 1.25)	2.3 (1.97 to 2.68)
Anti-14, POST(N=137;114)	3.96 (3.39 to 4.62)	5.41 (4.71 to 6.22)
Anti-18C, PRE(N=140;114)	0.62 (0.53 to 0.74)	2.58 (2.2 to 3.04)
Anti-18C, POST(N=137;114)	5.28 (4.55 to 6.12)	9.4 (8.04 to 10.98)
Anti-19F, PRE(N=140;114)	0.55 (0.44 to 0.7)	1.99 (1.65 to 2.4)
Anti-19F, POST(N=137;114)	3.38 (2.81 to 4.06)	5.71 (4.68 to 6.97)
Anti-23F, PRE(N=140;114)	0.48 (0.39 to 0.58)	0.57 (0.46 to 0.7)
Anti-23F, POST(N=137;114)	2.76 (2.37 to 3.21)	1.65 (1.33 to 2.03)

No statistical analyses for this end point

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

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End point title

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

End point description

Antibodies assessed for this outcome measure were those against the vaccine pneumococcal serotypes 6A, 19A (ANTI-6A, -19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL).Seropositivity = Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations >= 0.05 μg/mL. The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available (subjects from the 10Pn <6M & 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination).

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn for the < 6 months and 7-11 months groups

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	140	114
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A, PRE(N=140;114)	0.15 (0.12 to 0.19)	0.18 (0.14 to 0.23)
Anti-6A, POST(N=137;114)	0.52 (0.4 to 0.68)	0.55 (0.42 to 0.73)
Anti-19A, PRE(N=140;114)	0.1 (0.09 to 0.13)	0.26 (0.21 to 0.32)
Anti-19A, POST(N=137;114)	0.49 (0.39 to 0.61)	0.99 (0.78 to 1.25)

No statistical analyses for this end point

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

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End point title

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

End point description

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F >= 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available (subjects from the 10Pn <6M & 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination).

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn for the < 6 months and 7-11 months groups

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	51	40
Units: Titer
geometric mean (confidence interval 95%)
Opsono-1, PRE(N=51;38)	6 (4.5 to 8.1)	9.9 (5.8 to 16.9)
Opsono-1, POST(N=48;40)	188.4 (103.6 to 342.5)	234.1 (127.4 to 430.2)
Opsono-4, PRE(N=45;37)	22.2 (12.4 to 39.9)	94 (47.7 to 185.2)
Opsono-4, POST(N=48;38)	1486.3 (1138 to 1941)	978.3 (720.6 to 1328.1)
Opsono-5, PRE(N=48;37)	16 (11.1 to 23.1)	25.8 (16.3 to 41)
Opsono-5, POST(N=47;39)	143.8 (93.6 to 221)	243 (151.6 to 389.7)
Opsono-6B, PRE(N=45;31)	59.3 (29.3 to 120.1)	122.7 (50.3 to 299.5)
Opsono-6B, POST(N=45;40)	262 (130.3 to 526.5)	620.3 (356.5 to 1079.4)
Opsono-7F, PRE(N=49;33)	819.6 (471.8 to 1423.8)	1380.6 (730.3 to 2609.9)
Opsono-7F, POST(N=48;40)	4199.1 (3364.6 to 5240.6)	3726.8 (2759.4 to 5033.3)
Opsono-9V, PRE(N=50;37)	328.2 (245.4 to 438.8)	1427 (972.7 to 2093.4)
Opsono-9V, POST(N=48;38)	2198 (1718.6 to 2811.1)	2241.2 (1758.7 to 2856)
Opsono-14, PRE(N=46;37)	158.6 (82.6 to 304.6)	883.8 (597.9 to 1306.2)
Opsono-14, POST(N=48;40)	2224.7 (1674.1 to 2956.5)	1859.4 (1452.1 to 2380.9)
Opsono-18C, PRE(N=42;33)	6.5 (4.2 to 10)	395.9 (219.9 to 712.8)
Opsono-18C, POST(N=48;38)	650.3 (437.4 to 966.8)	1332.9 (926.3 to 1918)
Opsono-19F, PRE(N=49;38)	18.7 (12 to 29.3)	43.3 (23.3 to 80.4)
Opsono-19F, POST(N=47;38)	418.4 (237.8 to 736.4)	513.1 (265.8 to 990.2)
Opsono-23F, PRE(N=49;34)	700.6 (376.5 to 1303.9)	675.8 (293.2 to 1557.4)
Opsono-23F, POST(N=48;40)	3594.5 (2676.8 to 4826.8)	1770 (1148.4 to 2728)

No statistical analyses for this end point

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

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End point title

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

End point description

OPA titers against pneumococcal serotypes 6A, 19A (Opsono-6A, 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. Opsonophagocytic activity against cross-reactive pneumococcal serotypes 6A and 19A >= 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation. The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available (subjects from the 10Pn <6M & 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination).

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn for the < 6 months and 7-11 months groups

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	47	37
Units: Titer
geometric mean (confidence interval 95%)
Opsono-6A, PRE(N=41;33)	31.9 (15.9 to 63.9)	140.1 (69.2 to 283.3)
Opsono-6A, POST(N=43;36)	188.6 (96.9 to 367)	302.2 (168.7 to 541.5)
Opsono-19A, PRE(N=47;35)	5.7 (4.2 to 7.7)	7 (3.9 to 12.6)
Opsono-19A, POST(N=44;37)	16.1 (8.6 to 30.1)	36.8 (16.2 to 83.8)

No statistical analyses for this end point

Secondary: Antibody concentrations against protein D (Booster vaccination)

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End point title

Antibody concentrations against protein D (Booster vaccination)

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 milliliter (EL.U/mL) and tabulated. Seropositivity = Anti-PD antibody concentrations >= 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. The analysis was performed on the Booster According-To-Protocol(ATP) cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available (subjects from the 10Pn <6M & 7-11M groups for whom assay results were available for antibodies against at least one study vaccine antigen component after the booster vaccination).

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn for the < 6 months and 7-11 months groups

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	140	114
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD, PRE(N=140;114)	750.4 (631.2 to 892)	563.2 (475.5 to 666.9)
Anti-PD, POST(N=135;114)	2900.7 (2481.5 to 3390.8)	1942 (1614.5 to 2335.9)

No statistical analyses for this end point

Secondary: Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Primary vaccination)

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End point title

Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Primary vaccination) ^[2]

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per milliliter (IU/mL). Seroprotection status, defined as: Anti-D & anti-T antibody concentrations >=0.1 IU/mL. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only subjects in the 10Pn <6M Group received the Infanrix IPV/Hib (DTPa-IPV/Hib) vaccine.

End point values	10Pn <6M Group
Number of subjects analysed	132
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-D, POST-PRY (N=131)	0.961 (0.813 to 1.137)
Anti-T, POST-PRY (N=132)	2.38 (2.131 to 2.659)

No statistical analyses for this end point

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

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End point title

Anti-polyribosyl ribitol phosphate (PRP) antibody concentrations (Primary vaccination) ^[3]

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as micrograms per milliliter (µg/mL). Seroprotection status, defined as: anti-PRP antibody concentrations >=0.15 µg/mL and >= 1.0 µg/mL. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

Notes
[3] - 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: Only subjects in the 10Pn <6M Group received the Infanrix IPV/Hib (DTPa-IPV/Hib) vaccine.

End point values	10Pn <6M Group
Number of subjects analysed	132
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP , POST-PRY (N=132)	2.886 (2.305 to 3.615)

No statistical analyses for this end point

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

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End point title

Anti-pertussis toxoid (PT), anti-filamentous haemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations (Primary vaccination) ^[4]

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). Seropositivity status, defined as: Anti-PT, anti-FHA & anti-PRN antibody concentrations >= 5 EL.U/mL. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary vaccination course(Month [M]3 = POST-PRY) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

Notes
[4] - 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: Only subjects in the 10Pn <6M Group received the Infanrix IPV/Hib (DTPa-IPV/Hib) vaccine.

End point values	10Pn <6M Group
Number of subjects analysed	130
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PT, POST-PRY (N=129)	51.5 (46.5 to 57)
Anti-FHA, POST-PRY (N=127)	211.4 (192.7 to 231.8)
Anti-PRN, POST-PRY (N=130)	103.2 (90.7 to 117.4)

No statistical analyses for this end point

Secondary: Anti-polio type 1, 2 and 3 titers (Primary vaccination)

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End point title

Anti-polio type 1, 2 and 3 titers (Primary vaccination) ^[5]

End point description

Titers of antibodies are presented as geometric mean titers. Seroprotection status, defined as: Anti-polio type 1/2/3 titers >= 8. The analysis was performed on the Primary ATP cohort for immunogenicity, which included all evaluable subjects with immunogenicity data available for at least one study vaccine antigen component and at least one time point after primary vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, thus only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

At 1 month after the administration of the primary vaccination course (Month [M]3 = POST-PRY) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

Notes
[5] - 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: Only subjects in the 10Pn <6M Group received the Infanrix IPV/Hib (DTPa-IPV/Hib) vaccine.

End point values	10Pn <6M Group
Number of subjects analysed	17
Units: Titer
geometric mean (confidence interval 95%)
Anti-Polio 1, POST-PRY (N=17)	55.5 (30 to 102.6)
Anti-Polio 2, POST-PRY (N=16)	20.2 (9.7 to 41.9)
Anti-Polio 3, POST-PRY (N=16)	162.3 (73.5 to 358.5)

No statistical analyses for this end point

Secondary: Booster vaccine response to PT, FHA and PRN

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End point title

Booster vaccine response to PT, FHA and PRN

End point description

Booster vaccine response to PT, FHA and PRN, defined as appearance of antibodies in subjects who were seronegative (S-) prior to the booster dose (i.e., with concentrations < 5 EL.U/mL), and at least two-fold increase of pre-booster vaccination antibody concentrations in those who were seropositive (S+) prior to the booster dose (i.e., with concentrations >= 5 EL.U/ mL). Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from 10Pn <6M & 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

Before and one month after the booster dose with 10Pn

End point values	10Pn <6M Group
Number of subjects analysed	136
Units: Subjects
Anti-PT-Pre-booster status S- (N=14)	14
Anti-PT-Pre-booster status S+ (N=121)	117
Anti-FHA-Pre-booster status S- (N=0)	0
Anti-FHA-Pre-booster status S+ (N=136)	131
Anti-PRN-Pre-booster status S- (N=12)	12
Anti-PRN-Pre-booster status S+ (N=124)	123

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms (any and grade 3) (Primary vaccination)

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End point title

Number of subjects with solicited local symptoms (any and grade 3) (Primary vaccination)

End point description

Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm). Across doses= across the 3 doses (D1, D2 and D3) of the 10Pn-PD-DiT vaccine co-administered with Infranrix in the <6 months priming group; across the 2 doses of the 10Pn-PD-DiT vaccine in the 7-11 months priming group; across the 2 doses of the 10Pn-PD-DiT vaccine in the 12-23 months priming group and in the 1 dose of 10Pn-PD-DiT vaccine in the >=24 months priming group. The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary dose).

End point type

Secondary

End point timeframe

Within 4-Days (Days 0-3) following the primary vaccination

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	149	148	149	148
Units: Subjects
Any Pain, D1(N=149;148;149;148)	63	52	93	102
Grade 3 Pain, D1(N=149;148;149;148)	10	5	21	24
Any Redness, D1(N=149;148;149;148)	60	83	57	65
Grade 3 Redness, D1(N=149;148;149;148)	3	9	3	9
Any Swelling, D1(N=149;148;149;148)	37	48	39	32
Grade 3 Swelling, D1(N=149;148;149;148)	5	10	6	7
Any Pain, D2(N=146;147;143;0)	51	41	84	0
Grade 3 Pain, D2(N=146;147;143;0)	0	0	12	0
Any Redness, D2(N=146;147;143;0)	66	70	52	0
Grade 3 Redness, D2(N=146;147;143;0)	0	4	2	0
Any Swelling, D2(N=146;147;143;0)	38	39	38	0
Grade 3 Swelling, D2(N=146;147;143;0)	2	6	7	0
Any Pain, D3(N=145;0;0;0)	40	0	0	0
Grade 3 Pain, D3(N=145;0;0;0)	3	0	0	0
Any Redness, D3(N=145;0;0;0)	58	0	0	0
Grade 3 Redness, D3(N=145;0;0;0)	1	0	0	0
Any Swelling, D3(N=145;0;0;0)	33	0	0	0
Grade 3 Swelling, D3(N=145;0;0;0)	2	0	0	0
Any Pain, Across(N=149;148;149;148)	89	63	113	102
Grade 3 Pain, Across(N=149;148;149;148)	13	5	29	24
Any Redness, Across(N=149;148;149;148)	90	95	79	65
Grade 3 Redness, Across(N=149;148;149;148)	4	12	4	9
Any Swelling, Across(N=149;148;149;148)	68	66	59	32
Grade 3 Swelling, Across(N=149;148;149;148)	9	14	12	7

No statistical analyses for this end point

Secondary: Number of subjects with solicited local symptoms (any and grade 3) (Booster vaccination)

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End point title

Number of subjects with solicited local symptoms (any and grade 3) (Booster vaccination)

End point description

End point type

Secondary

End point timeframe

Within 4-Days (Days 0-3) following the booster vaccination

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	144	145
Units: Subjects
Any Pain	91	64
Grade 3 Pain	11	3
Any Redness	80	73
Grade 3 Redness	11	5
Any Swelling	55	45
Grade 3 Swelling	10	7

No statistical analyses for this end point

Secondary: Number of subjects with solicited general symptoms (any and grade 3) (Booster vaccination)

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End point title

Number of subjects with solicited general symptoms (any and grade 3) (Booster vaccination)

End point description

Assessed solicited general symptoms were Drowsiness, Irritability (Irr.), Loss of appetite (Loss Appet.) and Fever (rectal temperature higher than or equal to [>=] 38.0 degrees Celsius [°C]),. Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fussiness (Fuss). = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0 degrees Celsius (°C). The analysis was performed on the Booster Total Vaccinated, which cohort included all subjects from the 10Pn <6M & 10Pn 7-11M groups months groups, who received the booster dose.

End point type

Secondary

End point timeframe

Within 4-Days (Days 0-3) following the booster vaccination

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	144	145
Units: Subjects
Any Drowsiness	73	57
Grade 3 Drowsiness	3	3
Any Fever (Rectally)	63	33
Grade 3 Fever (Rectally)	1	0
Any Irritability	109	71
Grade 3 Irritability	5	3
Any Loss of Appet.	57	35
Grade 3 Loss of Appet.	1	3

No statistical analyses for this end point

Secondary: Number of subjects with unsolicited Adverse Events (AEs) (Primary vaccination)

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End point title

Number of subjects with unsolicited Adverse Events (AEs) (Primary vaccination)

End point description

An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination. The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary dose).

End point type

Secondary

End point timeframe

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

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	150	150	150	150
Units: Subjects
Any AEs	100	116	101	54

No statistical analyses for this end point

Secondary: Number of subjects with unsolicited Adverse Events (AEs) (Booster vaccination)

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End point title

Number of subjects with unsolicited Adverse Events (AEs) (Booster vaccination)

End point description

An unsolicited AE was defined as any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination. The analysis was performed on the Booster Total Vaccinated, which cohort included all subjects from the 10Pn <6M & 10Pn 7-11M groups months groups, who received the booster dose.

End point type

Secondary

End point timeframe

Within 31-Days (Days 0-30) following the booster vaccination

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	145	145
Units: Subjects
Any AEs	90	63

No statistical analyses for this end point

Secondary: Number of subjects with Serious Adverse Events (SAEs) (Primary vaccination)

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End point title

Number of subjects with Serious Adverse Events (SAEs) (Primary vaccination)

End point description

A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination. The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects (e.g. all subjects who received at least one primary dose).

End point type

Secondary

End point timeframe

During the Primary vaccination course up until start of Booster vaccination course

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	150	150	150	150
Units: Subjects
Any SAEs, Primary	17	5	2	0

No statistical analyses for this end point

Secondary: Number of subjects with Serious Adverse Events (SAEs) (Booster vaccination)

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End point title

Number of subjects with Serious Adverse Events (SAEs) (Booster vaccination)

End point description

A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of an SAE, regardless of relationship to vaccination. The analysis was performed on the Booster Total Vaccinated, which cohort included all subjects from the 10Pn <6M & 10Pn 7-11M groups, who received the booster dose.

End point type

Secondary

End point timeframe

During the booster vaccination course

End point values	10Pn <6M Group	10Pn 7-11M Group
Number of subjects analysed	145	145
Units: Subjects
Any SAEs, Booster	1	1

No statistical analyses for this end point

Secondary: Number of subjects with solicited general symptoms (Primary vaccination)

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End point title

Number of subjects with solicited general symptoms (Primary vaccination)

End point description

Assessed solicited general symptoms were Drowsiness, Irritability, Loss of appetite (Loss Appet.) and Fever (rectal temperature >=38.0 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature >40.0°C. Across doses= across the 3 doses [Dose 1(D1), Dose 2(D2) and Dose 3(D3)] of the 10Pn vaccine co-administered with Infranrix in the <6 months group; across the 2 doses of the 10Pn vaccine in the 7-11 months group; across the 2 doses of the 10Pn vaccine in the 12-23 months group and in the 1 dose of 10Pn vaccine in the >=24 months group. The analysis was performed on the Primary Total Vaccinated cohort, which included all vaccinated subjects.

End point type

Secondary

End point timeframe

Within 4-Days (Days 0-3) following the primary vaccination

End point values	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Number of subjects analysed	149	148	149	148
Units: Subjects
Drowsiness, D1(N=149;148;149;148)	101	70	63	55
Grade 3 Drowsiness, D1(N=149;148;149;148)	2	1	1	1
Any Fever (Rectally), D1(N=149;148;149;148)	54	34	30	10
Grade 3 Fever (Rectally), D1(N=149;148;149;148)	0	0	0	0
Any Irritability, D1(N=149;148;149;148)	122	90	90	62
Grade 3 Irritability, D1(N=149;148;149;148)	12	5	4	2
Any Loss of Appet, D1(N=149;148;149;148)	45	42	46	41
Grade 3 Loss of Appet., D1(N=149;148;149;148)	0	0	3	0
Any Drowsiness, D2(N=146;147;143;0)	64	51	48	0
Grade 3 Drowsiness, D2(N=146;147;143;0)	0	0	2	0
Any Fever (Rectally), D2(N=146 ;147;143;0)	60	34	24	0
Grade 3 Fever (Rectally), D2(N=146;147;143;0)	0	0	0	0
Any Irritability, D2(N=146;147;143;0)	103	78	62	0
Grade 3 Irritability, D2(N=146;147;143;0)	2	0	3	0
Any Loss of Appet., D2(N=146;147;143;0)	31	35	31	0
Grade 3 Loss of Appet., D2(N=146;147;143;0)	0	0	1	0
Any Drowsiness, D3(N=145;0;0;0)	53	0	0	0
Grade 3 Drowsiness, D3(N=145;0;0;0)	0	0	0	0
Any Fever (Rectally), D3(N=145 ;0;0;0)	40	0	0	0
Grade 3 Fever (Rectally), D3(N=145;0;0;0)	0	0	0	0
Any Irritability, D3(N=145;0;0;0)	83	0	0	0
Grade 3 Irritability, D3(N=145;0;0;0)	3	0	0	0
Any Loss of Appet., D3(N=145;0;0;0)	22	0	0	0
Grade 3 Loss of Appet., D3(N=145;0;0;0)	0	0	0	0
Any Drowsiness, Across(N=149;148;149;148)	122	92	90	55
Grade 3 Drowsiness, Across(N=149;148;149;148)	2	1	3	1
Any Fever (Rectally), Across(N=149;148;149;148)	95	55	47	10
Grade 3 Fever (Rectally),Across(N=149;148;149;148)	0	0	0	0
Any Irritability, Across(N=149;148;149;148)	143	112	107	62
Grade 3 Irritability, Across(N=149;148;149;148)	70	62	62	41
Grade 3 Loss of Appet., Across(N=149;148;149;148)	0	0	4	0

No statistical analyses for this end point

Secondary: Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Booster vaccination)

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End point title

Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Booster vaccination)

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per milliliter (IU/mL). Seroprotection status, defined as: Anti-D & anti-T antibody concentrations >= 0.1 IU/mL. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from 10Pn <6M & 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

End point values	10Pn <6M Group
Number of subjects analysed	140
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-D, PRE-BST (N=140)	0.218 (0.185 to 0.258)
Anti-D, POST-BST (N=137)	4.093 (3.578 to 4.683)
Anti-T, PRE-BST (N=140)	0.708 (0.616 to 0.813)
Anti-T, POST-BST (N=137)	10.245 (9.302 to 11.283)

No statistical analyses for this end point

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

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End point title

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

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as micrograms per milliliter (µg/mL). Seroprotection status, defined as: anti-PRP antibody concentrations >= 0.15 µg/mL and >= 1.0 µg/mL. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from 10Pn <6M & 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

End point values	10Pn <6M Group
Number of subjects analysed	140
Units: µg/mL;
geometric mean (confidence interval 95%)
Anti-PRP, PRE-BST (N=140)	0.458 (0.366 to 0.573)
Anti-PRP, POST-BST (N=136)	21.244 (16.778 to 26.9)

No statistical analyses for this end point

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

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End point title

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

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as enzyme-linked immunosorbent assay (ELISA) unit per milliliter (EL.U/mL). Seropositivity status, defined as: Anti-PT, anti-FHA & anti-PRN antibody concentrations >=5 EL.U/mL. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from 10Pn <6M & 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

End point values	10Pn <6M Group
Number of subjects analysed	140
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PT, PRE-BST (N=140)	11.2 (9.8 to 12.7)
Anti-PT, POST-BST (N=136)	88.6 (79.5 to 98.7)
Anti-FHA, PRE-BST (N=140)	49.2 (43.3 to 55.9)
Anti-FHA, POST-BST (N=137)	407.1 (368.5 to 449.8)
Anti-PRN, PRE-BST (N=140)	17.2 (14.7 to 20.1)
Anti-PRN, POST-BST (N=137)	276.6 (240.9 to 317.6)

No statistical analyses for this end point

Secondary: Titers of antibodies against polio type 1, 2 and 3 (Anti-polio 1, 2 and 3) (Booster vaccination)

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End point title

Titers of antibodies against polio type 1, 2 and 3 (Anti-polio 1, 2 and 3) (Booster vaccination)

End point description

Titers of antibodies are presented as geometric mean titers. Seroprotection status, defined as: Anti-polio type 1/2/3 titers >= 8. Since only "10Pn <6M Group" had received DTPa-IPV/Hib, therefore only that group was assessed for this Outcome. The analysis was performed on the Booster ATP cohort for immunogenicity, which included all evaluable subjects (from 10Pn <6M & 7-11M groups) for whom assay results were available for at least one study vaccine antigen after the booster vaccination. Only 10Pn <6M Group received DTPa-IPV/Hib, only that group was assessed for this Outcome.

End point type

Secondary

End point timeframe

Before (M9 = PRE-BST) and one month after the booster dose (M10 = POST-BST) with DTPa-IPV/Hib vaccine when co-administered with 10Pn, for the < 6 months Group

End point values	10Pn <6M Group
Number of subjects analysed	18
Units: Titer
geometric mean (confidence interval 95%)
Anti-Polio 1, PRE-BST (N=16)	19.1 (10.4 to 34.9)
Anti-Polio 1, POST-BST (N=13)	617 (302.3 to 1259.2)
Anti-Polio 2, PRE-BST (N=18)	14 (7.6 to 25.7)
Anti-Polio 2, POST-BST (N=13)	498.5 (198.1 to 1254.3)
Anti-Polio 3, PRE-BST (N=18)	20.1 (10.6 to 38.2)
Anti-Polio 3, POST-BST (N=13)	1234.1 (688.3 to 2212.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited & Unsolicited AEs: During the 4 & 31-Days post PRI/BST vaccination; SAEs: during PRI and BST Phases.

Adverse event reporting additional description

Note that 1) For 10Pn <6M Group & 10Pn 7-11M Group SAEs were reported during both PRI and BST Phases 2) The BST Phase safety follow-up is not applicable for the 10Pn 12-23M Group & 10Pn >=24M Group, as no booster doses were administered; to mark this, numbers of subjects for BST events for these groups are marked as equal to 1.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

11.0

Reporting group title

10Pn <6M Group

Reporting group description

This group consisted of subjects up to 6 months of age at first vaccination who received 3 doses of 10Pn-PD-DiT (or 10Pn) vaccine co-administered with InfanrixTM IPV/Hib (DTPa-IPV/Hib) at 3, 4 and 5 months of age and a booster dose of the same vaccines at 12-15 months of age. Vaccines were administrated intramuscularly in the right (10Pn-PD-DiT) or the left (DTPa-IPV/Hib) thigh or deltoid region (deltoid region only for children >12 months of age if muscle size was adequate).

Reporting group title

10Pn 7-11M Group

Reporting group description

Reporting group title

10Pn 12-23M Group

Reporting group description

Reporting group title

10Pn >=24M Group

Reporting group description

Serious adverse events	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Total subjects affected by serious adverse events
subjects affected / exposed	18 / 150 (12.00%)	6 / 150 (4.00%)	2 / 150 (1.33%)	0 / 150 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Gastrointestinal disorders
Abdominal pain upper - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (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
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 150 (1.33%)	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Psychomotor retardation - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (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
Pneumonia - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	2 / 150 (1.33%)	2 / 150 (1.33%)	2 / 150 (1.33%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	4 / 150 (2.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	2 / 150 (1.33%)	0 / 150 (0.00%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	3 / 150 (2.00%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 150 (0.00%)	2 / 150 (1.33%)	1 / 150 (0.67%)	0 / 150 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Exanthema subitum - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (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
Influenza - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (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
Respiratory syncytial virus bronchiolitis - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (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
Respiratory syncytial virus infection - PRI
alternative assessment type: Non-systematic
subjects affected / exposed	1 / 150 (0.67%)	0 / 150 (0.00%)	0 / 150 (0.00%)	0 / 150 (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
Bacterial infection - BST
alternative assessment type: Non-systematic
subjects affected / exposed ^[1]	1 / 145 (0.69%)	0 / 145 (0.00%)	0 / 1 (0.00%)	0 / 1 (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
Gastroenteritis - BST
alternative assessment type: Non-systematic
subjects affected / exposed ^[2]	0 / 145 (0.00%)	1 / 145 (0.69%)	0 / 1 (0.00%)	0 / 1 (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

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Assessment for this event for this phase was performed solely on subjects with available results.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Assessment for this event for this phase was performed solely on subjects with available results.

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

Non-serious adverse events	10Pn <6M Group	10Pn 7-11M Group	10Pn 12-23M Group	10Pn >=24M Group
Total subjects affected by non serious adverse events
subjects affected / exposed	149 / 150 (99.33%)	145 / 150 (96.67%)	144 / 150 (96.00%)	135 / 150 (90.00%)
General disorders and administration site conditions
Pain
subjects affected / exposed	114 / 150 (76.00%)	90 / 150 (60.00%)	113 / 150 (75.33%)	102 / 150 (68.00%)
occurrences all number	245	157	177	103
Erythema
subjects affected / exposed	109 / 150 (72.67%)	109 / 150 (72.67%)	79 / 150 (52.67%)	65 / 150 (43.33%)
occurrences all number	266	232	112	66
Swelling
subjects affected / exposed	88 / 150 (58.67%)	77 / 150 (51.33%)	59 / 150 (39.33%)	32 / 150 (21.33%)
occurrences all number	163	132	77	32
Somnolence
subjects affected / exposed	130 / 150 (86.67%)	103 / 150 (68.67%)	90 / 150 (60.00%)	56 / 150 (37.33%)
occurrences all number	291	178	111	57
Irritability
subjects affected / exposed	145 / 150 (96.67%)	124 / 150 (82.67%)	107 / 150 (71.33%)	63 / 150 (42.00%)
occurrences all number	426	241	152	64
Decreased appetite
subjects affected / exposed	94 / 150 (62.67%)	74 / 150 (49.33%)	62 / 150 (41.33%)	41 / 150 (27.33%)
occurrences all number	155	112	77	42
Injection site induration
alternative assessment type: Non-systematic
subjects affected / exposed	16 / 150 (10.67%)	12 / 150 (8.00%)	12 / 150 (8.00%)	1 / 150 (0.67%)
occurrences all number	22	14	15	1
Pyrexia
alternative assessment type: Non-systematic
subjects affected / exposed	120 / 150 (80.00%)	87 / 150 (58.00%)	60 / 150 (40.00%)	19 / 150 (12.67%)
occurrences all number	238	138	74	19
Injection site haematoma
subjects affected / exposed	9 / 150 (6.00%)	5 / 150 (3.33%)	0 / 150 (0.00%)	2 / 150 (1.33%)
occurrences all number	9	5	0	2
Eye disorders
Conjunctivitis
alternative assessment type: Non-systematic
subjects affected / exposed	7 / 150 (4.67%)	13 / 150 (8.67%)	4 / 150 (2.67%)	2 / 150 (1.33%)
occurrences all number	7	13	4	2
Gastrointestinal disorders
Diarrhoea
alternative assessment type: Non-systematic
subjects affected / exposed	11 / 150 (7.33%)	16 / 150 (10.67%)	14 / 150 (9.33%)	5 / 150 (3.33%)
occurrences all number	12	21	15	5
Teething
alternative assessment type: Non-systematic
subjects affected / exposed	14 / 150 (9.33%)	22 / 150 (14.67%)	4 / 150 (2.67%)	0 / 150 (0.00%)
occurrences all number	17	28	5	0
Vomiting
subjects affected / exposed	8 / 150 (5.33%)	9 / 150 (6.00%)	4 / 150 (2.67%)	1 / 150 (0.67%)
occurrences all number	8	9	4	1
Respiratory, thoracic and mediastinal disorders
Cough
alternative assessment type: Non-systematic
subjects affected / exposed	7 / 150 (4.67%)	20 / 150 (13.33%)	20 / 150 (13.33%)	5 / 150 (3.33%)
occurrences all number	8	22	24	6
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	8 / 150 (5.33%)	5 / 150 (3.33%)	4 / 150 (2.67%)	1 / 150 (0.67%)
occurrences all number	8	5	4	1
Infections and infestations
Nasopharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 150 (0.00%)	0 / 150 (0.00%)	11 / 150 (7.33%)	0 / 150 (0.00%)
occurrences all number	0	0	14	0
Otitis media
alternative assessment type: Non-systematic
subjects affected / exposed	19 / 150 (12.67%)	28 / 150 (18.67%)	20 / 150 (13.33%)	10 / 150 (6.67%)
occurrences all number	20	34	23	11
Rhinitis
alternative assessment type: Non-systematic
subjects affected / exposed	37 / 150 (24.67%)	33 / 150 (22.00%)	18 / 150 (12.00%)	4 / 150 (2.67%)
occurrences all number	52	47	22	4
Upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	60 / 150 (40.00%)	43 / 150 (28.67%)	21 / 150 (14.00%)	7 / 150 (4.67%)
occurrences all number	80	59	24	8
Ear infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 150 (0.00%)	15 / 150 (10.00%)	3 / 150 (2.00%)	0 / 150 (0.00%)
occurrences all number	0	18	3	0

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Were there any global substantial amendments to the protocol? Yes

28 Jun 2006

The protocol was amended to clarify in the study title that the assessment of immunogenicity, safety and reactogenicity would be done in children older than 7 months of age and in children before 6 months of age. Furthermore, because the post-licensure surveillance of Prevenar in the United States had shown a decrease and an increase in invasive pneumococcal disease caused by the cross-reactive pneumococcal serotypes 6A and 19A, respectively, it was of interest to document the immune responses (Enzyme-Linked Immuno-Sorbent Assay [ELISA] and opsonophagocytic activity [OPA]) to these cross-reactive pneumococcal serotypes. Also a higher flexibility of the distribution of replacement vial/syringe for the 10Pn-PD-DiT vaccine at the study centres was allowed as in each group all the children would receive the same vaccine.

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 with anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations greater than or equal to (>=)0.20 microgram per milliliter (µg/mL) (Primary/full vaccination)

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

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

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

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

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

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

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

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

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

Secondary: Antibody concentrations against protein D (anti-PD) (Primary/full vaccination)

Secondary: Antibody concentrations against protein D (anti-PD) (Primary/full vaccination)

Secondary: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >= 0.20 µg/mL (Booster vaccination)

Secondary: Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations >= 0.20 µg/mL (Booster vaccination)

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

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

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

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

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

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

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

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

Secondary: Antibody concentrations against protein D (Booster vaccination)

Secondary: Antibody concentrations against protein D (Booster vaccination)

Secondary: Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Primary vaccination)

Secondary: Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Primary vaccination)

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

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

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

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

Secondary: Anti-polio type 1, 2 and 3 titers (Primary vaccination)

Secondary: Anti-polio type 1, 2 and 3 titers (Primary vaccination)

Secondary: Booster vaccine response to PT, FHA and PRN

Secondary: Booster vaccine response to PT, FHA and PRN

Secondary: Number of subjects with solicited local symptoms (any and grade 3) (Primary vaccination)

Secondary: Number of subjects with solicited local symptoms (any and grade 3) (Primary vaccination)

Secondary: Number of subjects with solicited local symptoms (any and grade 3) (Booster vaccination)

Secondary: Number of subjects with solicited local symptoms (any and grade 3) (Booster vaccination)

Secondary: Number of subjects with solicited general symptoms (any and grade 3) (Booster vaccination)

Secondary: Number of subjects with solicited general symptoms (any and grade 3) (Booster vaccination)

Secondary: Number of subjects with unsolicited Adverse Events (AEs) (Primary vaccination)

Secondary: Number of subjects with unsolicited Adverse Events (AEs) (Primary vaccination)

Secondary: Number of subjects with unsolicited Adverse Events (AEs) (Booster vaccination)

Secondary: Number of subjects with unsolicited Adverse Events (AEs) (Booster vaccination)

Secondary: Number of subjects with Serious Adverse Events (SAEs) (Primary vaccination)

Secondary: Number of subjects with Serious Adverse Events (SAEs) (Primary vaccination)

Secondary: Number of subjects with Serious Adverse Events (SAEs) (Booster vaccination)

Secondary: Number of subjects with Serious Adverse Events (SAEs) (Booster vaccination)

Secondary: Number of subjects with solicited general symptoms (Primary vaccination)

Secondary: Number of subjects with solicited general symptoms (Primary vaccination)

Secondary: Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Booster vaccination)

Secondary: Anti-diphtheria (anti-D) and anti-tetanus toxoids (anti-T) antibody concentrations (Booster vaccination)

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

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

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

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

Secondary: Titers of antibodies against polio type 1, 2 and 3 (Anti-polio 1, 2 and 3) (Booster vaccination)

Secondary: Titers of antibodies against polio type 1, 2 and 3 (Anti-polio 1, 2 and 3) (Booster vaccination)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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