Clinical Trial Results:
A Phase 3, Randomized, Active-Controlled, Double-blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Pediatric Vaccinations in the United Kingdom

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2005-005130-12
Trial protocol	GB
Global end of trial date	21 Oct 2008

Results information
Results version number	v2(current)
This version publication date	28 Jul 2016
First version publication date	01 Aug 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set Not completed reason having type "Other" with same other reason text

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

6096A1-007

ISRCTN number

US NCT number

NCT00384059

WHO universal trial number (UTN)

Other trial identifiers

Alias: B1851090

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000036-PIP01-07

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

Yes

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

Analysis stage

Final

Date of interim/final analysis

13 Feb 2009

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Oct 2008

Was the trial ended prematurely?

Main objective of the trial

To evaluate the immune response induced by NeisVac-C (meningococcal group C vaccine) given with 13-valent Pneumococcal Conjugate Vaccine (13vPnC) relative to the immune response induced by NeisVac-C given with 7-valent pneumococcal conjugate vaccine (7vPnC) when measured 1 month after the infant series. The immune response was assessed using a meningococcal group C-specific serum bactericidal assay (SBA). To evaluate the immune responses induced by Pediacel given with 13vPnC relative to the immune responses induced by Pediacel given with 7vPnC when measured 1 month after the infant series. The immune responses to the following antigens in Pediacel were assessed: acellular pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbrial agglutinogens [FIM]) and Hib.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Oct 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

United Kingdom: 286

Worldwide total number of subjects

286

EEA total number of subjects

286

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)

286

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

Subjects were recruited in the United Kingdom (UK) from October 2006 to June 2007.

Screening details

Subjects were enrolled into the study according to inclusion/exclusion criteria without a screening period. Out of 286 subjects, demographic has been reported for 278, since demographic information for 8 subjects was unknown, as they were pre-randomized but not consented.

Period 1 title

Infant Series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC Infant Series

Arm description

Subjects received 13vPnC coadministered with meningococcal C-tetanus toxoid conjugate vaccine (NeisVac-C) and a combined diphtheria, tetanus, five component acellular pertussis (DT5aP), inactivated poliomyelitis (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (Pediacel) at the 2- and 4-month visit (infant series). Pediacel was administered without study vaccine at 3 month visit.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 13vPnC at 2 and 4 month (infant series).

Investigational medicinal product name

Pediacel

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of Pediacel at the 2, 3 and 4 month (infant series).

Investigational medicinal product name

NeisVac-C

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of NeisVac-C at 2 and 4 months of age (infant series).

7vPnC Infant Series

Arm description

Subjects received 7vPnC coadministered with meningococcal C-tetanus toxoid conjugate vaccine NeisVac-C and a combined DT5aP, IPV and Hib conjugate vaccine (Pediacel) at the 2- and 4-month visit (infant series). Pediacel was administered without study vaccine at 3-month visit.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 7vPnC at the 2 and 4 month (infant series).

Investigational medicinal product name

NeisVac-C

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of NeisVac-C at 2 and 4 month (infant series).

Investigational medicinal product name

Pediacel

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of Pediacel at 2, 3 and 4 months (infant series).

Number of subjects in period 1	13vPnC Infant Series	7vPnC Infant Series
Started	141	145
Vaccinated Dose 1	139	139
Vaccinated Dose 2	136	135
Completed	135	132
Not completed	6	13
Consent withdrawn by subject	2	2
Adverse Event	1	2
Protocol Violation	1	2
Not consented	2	6
Lost to follow-up	-	1

Period 2 title

After Infant Series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC After Infant Series

Arm description

Included subjects who received 13vPnC coadministered with NeisVac-C vaccine and a combined DT5aP, IPVand Hib conjugate vaccine (Pediacel) at at the 2 and 4month visits (infant series). Pediacel was administered without study vaccine at 3month visit.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

7vPnC After Infant Series

Arm description

Included subjects who received 7vPnC coadministered with NeisVac-C vaccine and a combined DT5aP, IPV and Hib conjugate vaccine (Pediacel) at at the 2- and 4-month visits (infant series). Pediacel was administered without study vaccine at 3-month visit.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	13vPnC After Infant Series	7vPnC After Infant Series
Started	135	132
Completed	131	122
Not completed	4	10
Consent withdrawn by subject	2	2
Physician decision	-	1
Failed to return	-	2
Adverse Event	-	1
Protocol Violation	2	3
Lost to follow-up	-	1

Period 3 title

Toddler Dose

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Subject, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC Toddler Dose

Arm description

Subjects recieved 13vPnC coadministered with Hib and Meningococcal C Vaccine (Menitorix) at the 12-month visit (toddler dose).

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 13vPnC at 12-month visit (toddler dose).

Investigational medicinal product name

Menitorix

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of Menitorix at the 12-month visit (toddler dose).

7vPnC Toddler Dose

Arm description

Subjects received 7vPnC coadministered with Hib and Meningococcal C Vaccine (Menitorix) at the 12-month visit (toddler dose).

Arm type

Active comparator

Investigational medicinal product name

Menitorix

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of Menitorix at the 12-month visit (toddler dose).

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects recieved one single 0.5 mL dose of 7vPnC at the 12-month visit (toddler dose).

Number of subjects in period 3	13vPnC Toddler Dose	7vPnC Toddler Dose
Started	131	122
Completed	130	120
Not completed	1	2
Failed to return	-	1
Lost to follow-up	1	1

Period 4 title

Baseline Period

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC

Arm description

Subjects received 13vPnC coadministered with NeisVac-C and a combined DT5aP, IPV and Hib conjugate vaccine (Pediacel) at the 2- and 4-month visits (infant series). Pediacel was administered without study vaccine at 3-month visit.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 13vPnC at 2 and 4 month (infant series).

Investigational medicinal product name

NeisVac-C

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of NeisVac-C at 2 and 4 months of age (infant series).

Investigational medicinal product name

Pediacel

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of Pediacel at the 2, 3 and 4 month (infant series).

7vPnC

Arm description

Subjects received 7vPnC coadministered with NeisVac-C and a combined DT5aP, IPV and Hib conjugate vaccine (Pediacel) at the 2- and 4-month visits (infant series). Pediacel was administered without study vaccine at 3-month visit.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of 7vPnC at 2 and 4 months of age (infant series).

Investigational medicinal product name

Pediacel

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of Pediacel at the 2, 3 and 4 month (infant series).

Investigational medicinal product name

NeisVac-C

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5-mL dose of NeisVac-C at 2 and 4 months of age (infant series).

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: The period 1 here does not represent the baseline period however period 4 is the baseline period as the baseline population is based on the evaluable infant immunogenicity population i.e., the primary immunogenicity analysis population.

Number of subjects in period 4 ^[2] ^[3]	13vPnC	7vPnC
Started	120	118
Completed	120	118

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The number of subjects reported in baseline period are not same as worldwide number because baseline period is based on the evaluable infant immunogenicity population i.e., the primary immunogenicity analysis population.
[3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Period 4 has been created to present the Baseline period and includes the data for evaluable infant immunogenicity population.

Baseline characteristics

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Reporting group title

13vPnC

Reporting group description

Reporting group title

7vPnC

Reporting group description

Reporting group values	13vPnC	7vPnC	Total
Number of subjects	120	118	238
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	2.1 ( 0.3 )	2.1 ( 0.2 )	-
Gender categorical
Units: Subjects
Female	55	57	112
Male	65	61	126

End points

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Reporting group title

13vPnC Infant Series

Reporting group description

Reporting group title

7vPnC Infant Series

Reporting group description

Reporting group title

13vPnC After Infant Series

Reporting group description

Reporting group title

7vPnC After Infant Series

Reporting group description

Reporting group title

13vPnC Toddler Dose

Reporting group description

Subjects recieved 13vPnC coadministered with Hib and Meningococcal C Vaccine (Menitorix) at the 12-month visit (toddler dose).

Reporting group title

7vPnC Toddler Dose

Reporting group description

Subjects received 7vPnC coadministered with Hib and Meningococcal C Vaccine (Menitorix) at the 12-month visit (toddler dose).

Reporting group title

13vPnC

Reporting group description

Reporting group title

7vPnC

Reporting group description

Subject analysis set title

13vPnC After Infant Series Dose 2

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C at the 2- and 4-month visits, Pediacel at the 2-, 3-, and 4-month visits.

Subject analysis set title

13vPnC Before Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C at the 2- and 4-month visits, Pediacel at the 2-, 3-, and 4-month visits.

Subject analysis set title

13vPnC After Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministrated with Menitorix at the 12-month visit.

Subject analysis set title

13vPnC Dose 1

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C and Pediacel at 2 months of age.

Subject analysis set title

7vPnC Dose 1

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with NeisVac-C and Pediacel at 2 months of age.

Subject analysis set title

13vPnC Dose 2

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C and Pediacel at 4 months of age.

Subject analysis set title

7vPnC Toddler Dose

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with Menitorix at 12 months of age.

Subject analysis set title

13vPnC Toddler Dose

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Menitorix at 12 months of age.

Subject analysis set title

7vPnC Dose 2

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with NeisVac-C and Pediacel at 4 months of age.

Subject analysis set title

13vPnC Before Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C at the 2- and 4-month visits, Pediacel at the 2-, 3-, and 4-month visits.

Subject analysis set title

7vPnC Before Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with NeisVac-C at the 2- and 4-month visits, Pediacel at the 2-, 3-, and 4-month visits.

Subject analysis set title

13vPnC After Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

'Subjects received one single 0.5 mL dose of 13vPnC coadministrated with Menitorix at the 12-month visit.

Subject analysis set title

7vPnC After Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministrated with Menitorix at the 12-month visit.

Primary: Percentage of Subjects Achieving a Meningococcal C Serum Bactericidal Assay (SBA) Titer >=1:8 and Predefined Antibody Levels for Pertussis and Haemophilus influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series.

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End point title

Percentage of Subjects Achieving a Meningococcal C Serum Bactericidal Assay (SBA) Titer >=1:8 and Predefined Antibody Levels for Pertussis and Haemophilus influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series.

End point description

Percentage of subjects achieving a meningococcal C SBA serum antibody titer greater than or equal to (>=) 1:8 and predefined antibody threshold levels with the corresponding 95 percent (%) confidence interval (CI) for concomitant antigens polyribosylribitol phosphate (PRP) in Haemophilus influenzae type b [Hib](>=0.15 microgram per milliliter (mcg/mL) or >=1.0 mcg/mL), pertussis toxoid [PT], filamentous haemagglutinin, pertactin [FHA], and pertactin (PRN) (>=5 enzyme-linked immunosorbent assay (ELISA) Units (EU)/mL) and fimbrial agglutinogens [FIM] (>=2.2/mL) are presented. Evaluable immunogenicity (per protocol) population consisting of eligible subjects who adhered to the protocol requirements, had valid and determinate assay results, and had no other major protocol violations; (n)= number of subjects with a determinate postinfant series antibody concentration to the given concomitant antigen.

End point type

Primary

End point timeframe

One month after infant series dose 2 (5 months of age)

End point values	13vPnC Infant Series	7vPnC Infant Series
Number of subjects analysed	120	118
Units: Percentage of subjects
number (confidence interval 95%)
Meningococcal C >= 1:8 titer (n=120,118)	99.2 (95.4 to 100)	99.2 (95.4 to 100)
Hib (PRP) >= 0.15 mcg/mL (n=114,102)	96.5 (91.3 to 99)	98 (93.1 to 99.8)
Hib (PRP) >= 1.0 mcg/mL (n=114,102)	85.1 (77.2 to 91.1)	89.2 (81.5 to 94.5)
Pertussis PT >= 5 EU/mL (n=119,112)	100 (96.9 to 100)	100 (96.8 to 100)
Pertussis PT >= 17 EU/mL (n=119,112)	96.6 (91.6 to 99.1)	95.5 (89.9 to 98.5)
Pertussis FHA >= 5 EU/mL (n=119,113)	100 (96.9 to 100)	100 (96.8 to 100)
Pertussis FHA >= 7.82 EU/mL (n=119,113)	100 (96.9 to 100)	100 (96.8 to 100)
Pertussis FHA >= 20 EU/mL (n=119,113)	94.1 (88.3 to 97.6)	95.6 (90 to 98.5)
Pertussis PRN >= 5 EU/mL (n=119,113)	100 (96.9 to 100)	100 (96.8 to 100)
Pertussis PRN >= 15 EU/mL (n=119,113)	92.4 (86.1 to 96.5)	95.6 (90 to 98.5)
Pertussis FIM >= 2.2 EU/mL (n=119,113)	100 (96.9 to 100)	97.3 (92.4 to 99.4)
Pertussis FIM >= 5 EU/mL (n=119,113)	97.5 (92.8 to 99.5)	96.5 (91.2 to 99)

Analysis for Meningococcal C >=1:8 titer

Statistical analysis description

For Meningococcal C the difference in percentage between the two groups (13vPnC - 7vPnC) at 1:8 titer was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

3.9

Notes
[1] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC - 7vPnC) greater than (>) -10%.

Analysis for Hib (PRP) >=0.15 mcg/mL

Statistical analysis description

For Haemophilus influenzae type b the difference in percentage between the two groups (13vPnC - 7vPnC) at 0.15 mcg/mL threshold was calculated.

Comparison groups

7vPnC Infant Series v 13vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Difference

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

3.7

Notes
[2] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis PT >=5 EU/mL

Statistical analysis description

For Pertussis PT the difference in percentage between the two groups (13vPnC - 7vPnC) at 5 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

3.3

Notes
[3] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Hib (PRP) >=1.0 mcg/mL

Statistical analysis description

For Haemophilus influenzae type b the difference in percentage between the two groups (13vPnC - 7vPnC) at 1.0 mcg/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Difference

Point estimate

-4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-13.4

upper limit

5.1

Notes
[4] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis PT >=17 EU/mL

Statistical analysis description

For Pertussis PT the difference in percentage between the two groups (13vPnC - 7vPnC) at 17 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Difference

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

7.1

Notes
[5] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis FHA >=5 EU/mL

Statistical analysis description

For Pertussis FHA the difference in percentage between the two groups (13vPnC - 7vPnC) at 5 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

3.2

Notes
[6] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis FHA >=7.82 EU/mL

Statistical analysis description

For Pertussis FHA the difference in percentage between the two groups (13vPnC - 7vPnC) at 7.82 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

3.2

Notes
[7] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis FHA >=20 EU/mL

Statistical analysis description

For Pertussis FHA the difference in percentage between the two groups (13vPnC - 7vPnC) at 20 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Difference

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

4.8

Notes
[8] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis PRN >= 5 EU/mL

Statistical analysis description

For Pertussis PRN the difference in percentage between the two groups (13vPnC - 7vPnC) at 5 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

3.2

Notes
[9] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis PRN >=15 EU/mL

Statistical analysis description

For Pertussis PRN the difference in percentage between the two groups (13vPnC - 7vPnC) at 15 EU/mL threshold was calculated.

Comparison groups

7vPnC Infant Series v 13vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Difference

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-10

upper limit

3.4

Notes
[10] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis FIM >=2.2 EU/mL

Statistical analysis description

For Pertussis FIM the difference in percentage between the two groups (13vPnC - 7vPnC) at 2.2 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

Difference

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

7.6

Notes
[11] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Analysis for Pertussis FIM >=5 EU/mL

Statistical analysis description

For Pertussis FIM the difference in percentage between the two groups (13vPnC - 7vPnC) at 5 EU/mL threshold was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

6.5

Notes
[12] - Non-inferiority for concomitant antigens was declared if the lower limit of 2-sided 95% CI for the difference between the 2 groups (13vPnC – 7vPnC) > -10%.

Primary: Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

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End point title

Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

End point description

End point type

Primary

End point timeframe

One month after infant series dose 2 (5 months of age)

End point values	13vPnC Infant Series	7vPnC Infant Series
Number of subjects analysed	120 ^[13]	118 ^[14]
Units: titer
geometric mean (confidence interval 95%)	306.2 (251.21 to 373.22)	345.42 (287.91 to 414.41)

Notes
[13] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen
[14] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen

Analysis for Meningococcal C

Statistical analysis description

For Meningococcal C the geometric mean concentration (GMC) ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

Parameter type

Ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.16

Notes
[15] - Non-inferiority for the concomitant antigens was declared if the lower bound of the 2-sided, 95% CI for the GMC ratio (13vPnC group/7vPnC group) was >0.5 (2-fold criterion).

Primary: Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Top of page

End point title

Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

End point description

End point type

Primary

End point timeframe

One month after infant series dose 2 (5 months of age)

End point values	13vPnC Infant Series	7vPnC Infant Series
Number of subjects analysed	114 ^[16]	102 ^[17]
Units: microgram per milliliter (mcg/mL)
geometric mean (confidence interval 95%)	3.4 (2.65 to 4.37)	4.44 (3.5 to 5.63)

Notes
[16] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen
[17] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen

Analysis of GMC for Hib

Statistical analysis description

For Hib the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

216

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

Ratio

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.08

Notes
[18] - Non-inferiority for the concomitant antigens was declared if the lower bound of the 2-sided, 95% CI for the GMC ratio (13vPnC group/7vPnC group) was >0.5 (2-fold criterion).

Primary: Geometric Mean Antibody Concentration of Pertusis Filamentous Haemagglutinin (FHA), Pertussis Toxoid (PT), Pertactin (PRN), and Fimbrial Agglutinogens (FIM) as Measured by ELISA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Top of page

End point title

Geometric Mean Antibody Concentration of Pertusis Filamentous Haemagglutinin (FHA), Pertussis Toxoid (PT), Pertactin (PRN), and Fimbrial Agglutinogens (FIM) as Measured by ELISA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

End point description

Evaluable immunogenicity (per protocol) population consisting of eligible subjects who adhered to the protocol requirements, had valid and determinate assay results, and had no other major protocol violations. (n) = number of subjects with a determinate antibody concentration/titer for the specified concomitant antigen.

End point type

Primary

End point timeframe

One month after infant series dose 2 (5 months of age)

End point values	13vPnC Infant Series	7vPnC Infant Series
Number of subjects analysed	120	118
Units: EU/mL
geometric mean (confidence interval 95%)
Pertussis FHA (n=119,113)	54.74 (48.25 to 62.09)	55.99 (49.55 to 63.28)
Pertussis PT (n=119,112)	66.26 (59.2 to 74.16)	67.05 (58.75 to 76.52)
Pertussis PRN (n=119,113)	61.33 (51.78 to 72.65)	61.07 (52.31 to 71.3)
Pertussis FIM (n=119,113)	21.72 (18.89 to 24.98)	21.77 (18.54 to 25.56)

Analysis of GMC for Pertussis FHA

Statistical analysis description

For Pertussis FHA the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

Parameter type

Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.16

Notes
[19] - Non-inferiority for the concomitant antigens was declared if the lower bound of the 2-sided, 95% CI for the GMC ratio (13vPnC group/7vPnC group) was >0.5 (2-fold criterion).

Analysis of GMC for Pertussis PT

Statistical analysis description

For Pertussis PT the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

Parameter type

Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.17

Notes
[20] - Non-inferiority for the concomitant antigens was declared if the lower bound of the 2-sided, 95% CI for the GMC ratio (13vPnC group/7vPnC group) was >0.5 (2-fold criterion).

Analysis of GMC for Pertussis PRN

Statistical analysis description

For Pertussis PRN the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.26

Notes
[21] - Non-inferiority for the concomitant antigens was declared if the lower bound of the 2-sided, 95% CI for the GMC ratio (13vPnC group/7vPnC group) was >0.5 (2-fold criterion).

Analysis of GMC for Pertussis FIM

Statistical analysis description

For Pertussis FIM the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Infant Series v 7vPnC Infant Series

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.23

Notes
[22] - Non-inferiority for the concomitant antigens was declared if the lower bound of the 2-sided, 95% CI for the GMC ratio (13vPnC group/7vPnC group) was >0.5 (2-fold criterion).

Primary: Percentage of Subjects in the 13vPnC Group Achieving a Serotype-specific IgG Antibody Concentration >=0.35 mcg/mL Measured 1 Month After the 2-dose Infant Series, Before and After the Toddler Dose

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End point title

Percentage of Subjects in the 13vPnC Group Achieving a Serotype-specific IgG Antibody Concentration >=0.35 mcg/mL Measured 1 Month After the 2-dose Infant Series, Before and After the Toddler Dose ^[23]

End point description

Percentages of subjects achieving WHO predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Evaluable immunogenicity (per protocol) population consisting of eligible subjects who adhered to protocol requirements, had valid and determinate assay results, and had no other major protocol violations; (n) = number of subjects with a determinate IgG antibody concentration to the given serotype.

End point type

Primary

End point timeframe

One month after infant series dose 2 (5 months of age), before and after toddler dose (12 months of age)

Notes
[23] - 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: Only descriptive data was planned to be reported for this endpoint.

End point values	13vPnC After Infant Series Dose 2	13vPnC Before Toddler Dose	13vPnC After Toddler Dose
Number of subjects analysed	120	120	110
Units: Percentage of subjects
number (confidence interval 95%)
Common Serotypes - Serotype 4 (n=107,89,102)	95.3 (89.4 to 98.5)	24.7 (16.2 to 35)	99 (94.7 to 100)
Common Serotypes - Serotype 6B (n=107,86,102)	40.2 (30.8 to 50.1)	74.4 (63.9 to 83.2)	98 (93.1 to 99.8)
Common Serotypes - Serotype 9V (n=104,91,101)	85.6 (77.3 to 91.7)	44 (33.6 to 54.8)	98 (93 to 99.8)
Common Serotypes - Serotype 14 (n=107,88,101)	92.5 (85.8 to 96.7)	92 (84.3 to 96.7)	100 (96.4 to 100)
Common Serotypes - Serotype 18C (n=111,91,105)	92.8 (86.3 to 96.8)	13.2 (7 to 21.9)	97.1 (91.9 to 99.4)
Common Serotypes - Serotype 19F (n=109,91,104)	93.6 (87.2 to 97.4)	67 (56.4 to 76.5)	98.1 (93.2 to 99.8)
Common Serotypes - Serotype 23F (n=111,89,104)	66.7 (57.1 to 75.3)	37.1 (27.1 to 48)	98.1 (93.2 to 99.8)
Additional Serotypes - Serotype 1 (n=107,88,101)	97.2 (92 to 99.4)	50 (39.1 to 60.9)	100 (96.4 to 100)
Additional Serotypes - Serotype 3 (n=107,87,102)	86 (77.9 to 91.9)	12.6 (6.5 to 21.5)	88.2 (80.4 to 93.8)
Additional Serotypes - Serotype 5 (n=103,88,101)	89.3 (81.7 to 94.5)	78.4 (68.4 to 86.5)	100 (96.4 to 100)
Additional Serotypes - Serotype 6A (n=106,86,99)	79.2 (70.3 to 86.5)	79.1 (69 to 87.1)	98 (92.9 to 99.8)
Additional Serotypes - Serotype 7F (n=107,91,100)	94.4 (88.2 to 97.9)	71.4 (61 to 80.4)	100 (96.4 to 100)
Additional Serotypes - Serotype 19A (n=110,91,103)	92.7 (86.2 to 96.8)	86.8 (78.1 to 93)	100 (96.5 to 100)

No statistical analyses for this end point

Primary: Geometric Mean Antibody Concentration in 13vPnC Group After the 2-dose Infant Series, Before and After the Toddler Dose

Top of page

End point title

Geometric Mean Antibody Concentration in 13vPnC Group After the 2-dose Infant Series, Before and After the Toddler Dose ^[24]

End point description

Antibody concentration/geometric mean concentration (GMC) as measured by ELISA for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented with corresponding 2-sided 95% CI. Evaluable immunogenicity (per protocol) population consisting of eligible subjects who adhered to protocol requirements, had valid and determinate assay results, and had no other major protocol violations; (n) = number of subjects with a determinate antibody concentration for the specified serotype.

End point type

Primary

End point timeframe

One month after infant series dose 2 (5 months of age) and before and after toddler dose (12 months of age)

Notes
[24] - 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: Only descriptive data was planned to be reported for this endpoint.

End point values	13vPnC After Infant Series Dose 2	13vPnC Before Toddler Dose	13vPnC After Toddler Dose
Number of subjects analysed	120	120	110
Units: mcg/mL
geometric mean (confidence interval 95%)
Common Serotypes - Serotype 4 (n=107,87,87)	1.37 (1.16 to 1.62)	0.21 (0.17 to 0.24)	3.52 (2.91 to 4.26)
Common Serotypes - Serotype 6B (n=107,85,85)	0.26 (0.21 to 0.33)	0.77 (0.6 to 0.99)	7.67 (5.88 to 10.01)
Common Serotypes - Serotype 9V (n=104,88,88)	0.87 (0.72 to 1.05)	0.29 (0.24 to 0.36)	2.46 (2.03 to 2.99)
Common Serotypes - Serotype 14 (n=107,87,87)	1.83 (1.47 to 2.27)	1.34 (1.09 to 1.66)	11.32 (9.27 to 13.83)
Common Serotypes - Serotype 18C (n=111,91,91)	1.37 (1.14 to 1.64)	0.2 (0.17 to 0.23)	2.14 (1.82 to 2.53)
Common Serotypes - Serotype 19F (n=109,90,90)	2.38 (1.88 to 3.01)	0.6 (0.46 to 0.79)	7.25 (5.65 to 9.31)
Common Serotypes - Serotype 23F (n=111,88,88)	0.53 (0.42 to 0.67)	0.24 (0.19 to 0.32)	3.13 (2.59 to 3.78)
Additional Serotypes - Serotype 1 (n=107,85,85)	1.69 (1.41 to 2.04)	0.39 (0.33 to 0.46)	5.6 (4.6 to 6.82)
Additional Serotypes - Serotype 3 (n=107,85,85)	0.63 (0.56 to 0.71)	0.14 (0.1 to 0.18)	0.98 (0.78 to 1.22)
Additional Serotypes - Serotype 5 (n=103,86,86)	0.95 (0.79 to 1.14)	0.59 (0.49 to 0.72)	3.68 (3.04 to 4.45)
Additional Serotypes - Serotype 6A (n=106,83,83)	0.86 (0.68 to 1.07)	0.81 (0.64 to 1.03)	6.31 (5.06 to 7.87)
Additional Serotypes - Serotype 7F (n=107,87,87)	2.14 (1.75 to 2.62)	0.56 (0.48 to 0.66)	4.06 (3.42 to 4.83)
Additional Serotypes - Serotype 19A (n=110,89,89)	1.9 (1.54 to 2.34)	1.01 (0.77 to 1.32)	11.33 (9.29 to 13.83)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving an SBA Titer >=1:8 for Meningococcal C in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose

Top of page

End point title

Percentage of Subjects Achieving an SBA Titer >=1:8 for Meningococcal C in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose

End point description

Evaluable immunogenicity (per protocol) population consisting of eligible subjects who adhered to protocol requirements, had valid and determinate assay results, and had no other major protocol violations; (n)= number of subjects with a determinate posttoddler dose antibody concentration to the given concomitant antigen.

End point type

Secondary

End point timeframe

Before and 1 month after the toddler dose (13 months of age)

End point values	13vPnC Before Toddler Dose	7vPnC Before Toddler Dose	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	102	93	109	98
Units: Percentage of Subjects
number (confidence interval 95%)	44.1 (34.3 to 54.3)	49.5 (38.9 to 60)	91.7 (84.9 to 96.2)	91.8 (84.5 to 96.4)

Meningococcal C: After Toddler Dose

Statistical analysis description

For Meningococcal C the difference in percentage between the two groups (13vPnC - 7vPnC) at 1:8 titer was calculated.

Comparison groups

7vPnC After Toddler Dose v 13vPnC After Toddler Dose

Number of subjects included in analysis

207

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

Parameter type

Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

8.1

Notes
[25] - Non-inferiority was used to assess, but the study has not been powered to show non-inferiority.

Meningococcal C: Before Toddler Dose

Statistical analysis description

For Meningococcal C the difference in percentage between the two groups (13vPnC - 7vPnC) at 1:8 titer was calculated.

Comparison groups

13vPnC Before Toddler Dose v 7vPnC Before Toddler Dose

Number of subjects included in analysis

195

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

Parameter type

Difference

Point estimate

-5.3

Confidence interval

level

95%

sides

2-sided

lower limit

-19.7

upper limit

8.8

Notes
[26] - Non-inferiority was used to assess, but the study has not been powered to show non-inferiority.

Secondary: Percentage of Subjects Achieving a Predefined Antibody Level for Haemophilus Influenzae Type b in the 13vPnC Group Relative to the 7vPnC Group After the Toddler Dose

Top of page

End point title

Percentage of Subjects Achieving a Predefined Antibody Level for Haemophilus Influenzae Type b in the 13vPnC Group Relative to the 7vPnC Group After the Toddler Dose

End point description

End point type

Secondary

End point timeframe

One month after toddler dose (13 months of age)

End point values	13vPnC Toddler Dose	7vPnC Toddler Dose
Number of subjects analysed	105 ^[27]	96 ^[28]
Units: Percentage of subjects
number (confidence interval 95%)
Hib (PRP) >=0.15 mcg/mL	100 (96.5 to 100)	100 (96.2 to 100)
Hib (PRP)>=1.0 mcg/mL	99 (94.8 to 100)	100 (96.2 to 100)

Notes
[27] - Subjects with determinate posttoddler dose antibody concentration to given concomitant antigen
[28] - Subjects with determinate posttoddler dose antibody concentration to given concomitant antigen

Analysis for Hib at 1.0 mcg/mL

Statistical analysis description

For Hib the difference in percentage between the two groups (13vPnC - 7vPnC) at 1.0 mcg/mL threshold was calculated.

Comparison groups

13vPnC Toddler Dose v 7vPnC Toddler Dose

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

2.8

Notes
[29] - Non-inferiority was used to assess, but the study has not been powered to show non-inferiority.

Analysis for Hib at 0.15 mcg/mL

Statistical analysis description

For Hib the difference in percentage between the two groups (13vPnC - 7vPnC) at 0.15 mcg/mL threshold was calculated.

Comparison groups

7vPnC Toddler Dose v 13vPnC Toddler Dose

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

3.8

Notes
[30] - Non-inferiority was used to assess, but the study has not been powered to show non-inferiority.

Secondary: Geometric Mean Antibody Concentration for Haemophilus Influenzae Type b PRP in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

Top of page

End point title

Geometric Mean Antibody Concentration for Haemophilus Influenzae Type b PRP in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

End point description

Evaluable immunogenicity (per protocol) population of eligible subjects who adhered to protocol requirements, had valid and determinate assay results, and had no other major protocol violations.

End point type

Secondary

End point timeframe

One month after toddler dose (13 months of age)

End point values	13vPnC Toddler Dose	7vPnC Toddler Dose
Number of subjects analysed	105 ^[31]	96 ^[32]
Units: mcg/mL
geometric mean (confidence interval 95%)	22.22 (17.66 to 27.96)	19.75 (16.05 to 24.3)

Notes
[31] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen
[32] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen

Analysis of GMC for Hib PRP

Statistical analysis description

For Hib the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Toddler Dose v 7vPnC Toddler Dose

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

Method

Parameter type

Ratio

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.53

Notes
[33] - Non-inferiority was used to assess, but the study has not been powered to show non-inferiority.

Secondary: Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

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End point title

Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

End point description

End point type

Secondary

End point timeframe

One month after toddler dose (13 months of age)

End point values	13vPnC Toddler Dose	7vPnC Toddler Dose
Number of subjects analysed	109 ^[34]	98 ^[35]
Units: titer
geometric mean (confidence interval 95%)	656.11 (445.46 to 966.38)	771.67 (509.98 to 1167.64)

Notes
[34] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen
[35] - N=number of subjects with determinate antibody concentration/titer for specified concomitant antigen

Analysis of GMC for Meningococcal C

Statistical analysis description

For Meningococcal C the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC Toddler Dose v 7vPnC Toddler Dose

Number of subjects included in analysis

207

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.49

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions

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End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions

End point description

Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category. The safety population included all subjects who received at least 1 dose of vaccine; (n)= number of subjects reporting yes for at least 1 day or no for all days.

End point type

Other pre-specified

End point timeframe

During the 4-day period after each dose

End point values	13vPnC Dose 1	7vPnC Dose 1	13vPnC Dose 2	7vPnC Toddler Dose	13vPnC Toddler Dose	7vPnC Dose 2
Number of subjects analysed	139	139	136	122	131	135
Units: Percentage of Subjects
number (not applicable)
Tenderness-Any (n=123,127,114,96,87,71)	44.7	43.3	42.1	50.7	44.8	40.6
Tenderness-Significant (n=116,122,97,89,77,58)	1.7	6.6	4.1	3.4	3.9	4.5
Swelling-Any (n=121,126,106,93,83,68)	24.8	29.4	30.2	39.7	30.1	34.4
Swelling-Mild (n=120,125,105,93,82,66)	21.7	27.2	28.6	34.8	28	29
Swelling-Moderate (n=118,121,98,88,77,60)	6.8	6.6	8.2	11.7	3.9	6.8
Swelling-Severe (n=115,119,96,88,76,57)	0	0	1	0	0	0
Redness-Any (n=122,126,107,99,85,73)	22.1	39.7	39.3	53.4	38.8	40.4
Redness-Mild (n=122,126,106,99,83,71)	21.3	39.7	37.7	49.3	33.7	37.4
Redness-Moderate (n=116,119,98,88,78,61)	1.7	0	4.1	16.4	12.8	3.4
Redness-Severe (n=115,119,97,88,76,57)	0	0	2.1	0	0	0

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events

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End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events

End point description

Systemic events (fever >= 38 degrees Celsius [C] but <= 39 C, fever >39 C but <= 40 C, fever > 40 C, decreased appetite, irritability, increased sleep, decreased sleep, use of medication (Meds) to prevent symptoms, and use of medication to treat symptoms) were collected using an electronic diary; percentage of subjects with each event was evaluated. Safety population included all subjects who received at least 1 dose of vaccine. (n) = number of subjects reporting yes for at least 1 day or no for all days.

End point type

Other pre-specified

End point timeframe

During the 4-day period after each dose

End point values	13vPnC Dose 1	7vPnC Dose 1	13vPnC Dose 2	7vPnC Toddler Dose	13vPnC Toddler Dose	7vPnC Dose 2
Number of subjects analysed	139	139	136	122	131	135
Units: Percentage of Subjects
number (not applicable)
Fever >=38°C but <=39°C (n=116,119,96,88,78,61)	6	3.4	3.1	16.4	7.7	4.5
Fever >39°C but <=40°C (n=115,119,95,88,76,58)	0.9	0	0	5.2	0	0
Fever >40°C (n=115,119,96,88,76,57)	0	0	2.1	0	0	0
Decreased appetite (n=120,129,104,98,92,68)	39.2	34.1	35.6	44.1	39.1	37.8
Irritability (n=128,135,117,119,97,80)	76.6	74.1	71.8	76.3	74.2	80.7
Increased sleep (n=129,129,114,109,88,71)	69.8	66.7	51.8	40.8	38.6	56.9
Decreased sleep (n=119,124,98,100,81,67)	32.8	33.9	35.7	44.8	32.1	38
Meds to treat symptoms (n=123,128,108,110,85,72)	43.9	40.6	50.9	58.3	49.4	54.5
Meds to prevent symptoms (n=122,124,117,103,92,77)	49.2	40.3	48.7	67.5	52.2	50.5

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse Events (AEs)/Serious AEs: recorded from sigining of informed consent to 6 months after the last study vaccination. Subjects recorded pre-specified AEs in electronic diary:local reactions; systemic events (up to 4 days after each vaccination)

Adverse event reporting additional description

MedDRA Version was not captured, here 0.0 is mentioned for dictionary version. Local Reactions (LRs) and Systemic Events (SEs) were to be assessed only for infant series and toddler dose groups.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

0.0

Reporting group title

13vPnC Infant Series

Reporting group description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C and a DT5aP, IPV and Hib conjugate vaccine (Pediacel) at the 2- and 4-month visits (AE/SAE assessment at 5 months of age, 1 month after the infant series). Pediacel was administered without study vaccine at 3-month visit.

Reporting group title

7vPnC Infant Series

Reporting group description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with NeisVac-C and a DT5aP, IPV and Hib conjugate vaccine (Pediacel) at the 2- and 4-month visits (AE/SAE assessment at 5 months of age, 1 month after the infant series). Pediacel was administered without study vaccine at 3-month visit.

Reporting group title

13vPnC After Infant Series

Reporting group description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with NeisVac-C and a DT5aP, IPV and Hib conjugate vaccine Pediacel at the 2- and 4-month visits (AE/SAE assessment at 5 months of age, 1 month after the infant dose to before toddler dose). Pediacel was administered without study vaccine at 3-month visit.

Reporting group title

7vPnC After Infant Series

Reporting group description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with NeisVac-C and a DT5aP, IPV and Hib conjugate vaccine (Pediacel) at the 2- and 4-month visits (AE/SAE assessment at 5 months of age, 1 month after the infant dose to before toddler dose). Pediacel was administered without study vaccine at 3-month visit.

Reporting group title

13vPnC Toddler Series

Reporting group description

Subjects recieved one single 0.5 mL dose of 13vPnC coadministered with Hib and Menitorix at the 12-month visit (toddler dose). AE/SAE assessment at 1 month after the toddler dose.

Reporting group title

7vPnC Toddler Series

Reporting group description

Subjects recieved one single 0.5 mL dose of 7vPnC coadministered with Hib and Menitorix at the 12-month visit (toddler dose). AE/SAE assessment at 1 month after the toddler dose.

Reporting group title

13vPnC 6-Month Follow-up

Reporting group description

Subjects recieved one single 0.5 mL dose of 13vPnC coadministered with Hib and Menitorix at the 12-month visit (AE/SAE assessment at 18 months of age, 6 months after the toddler dose).

Reporting group title

7vPnC 6-Month Follow-up

Reporting group description

Subjects recieved one single 0.5 mL dose of 7vPnC coadministered with Hib and Menitorix at the 12-month visit (AE/SAE assessment at 18 months of age, 6 months after the toddler dose).

Serious adverse events	13vPnC Infant Series	7vPnC Infant Series	13vPnC After Infant Series	7vPnC After Infant Series	13vPnC Toddler Series	7vPnC Toddler Series	13vPnC 6-Month Follow-up	7vPnC 6-Month Follow-up
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 138 (0.72%)	3 / 139 (2.16%)	5 / 138 (3.62%)	2 / 139 (1.44%)	1 / 130 (0.77%)	2 / 122 (1.64%)	2 / 138 (1.45%)	0 / 139 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tongue injury
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemiplegia
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Wheezing
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Breath holding
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mastoiditis
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	13vPnC Infant Series	7vPnC Infant Series	13vPnC After Infant Series	7vPnC After Infant Series	13vPnC Toddler Series	7vPnC Toddler Series	13vPnC 6-Month Follow-up	7vPnC 6-Month Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	128 / 138 (92.75%)	124 / 139 (89.21%)	9 / 138 (6.52%)	8 / 139 (5.76%)	87 / 130 (66.92%)	82 / 122 (67.21%)	1 / 138 (0.72%)	1 / 139 (0.72%)
Vascular disorders
Flushing
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0
General disorders and administration site conditions
Gait disturbance
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0
Pyrexia
subjects affected / exposed	9 / 138 (6.52%)	7 / 139 (5.04%)	0 / 138 (0.00%)	0 / 139 (0.00%)	5 / 130 (3.85%)	6 / 122 (4.92%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	12	7	0	0	5	6	0	0
Injection site erythema
subjects affected / exposed	1 / 138 (0.72%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0
Feeling hot
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Injection site bruising
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0
Irritability
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
Vessel puncture site haematoma
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Injection site induration
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Injection site swelling
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Fever >=38 degree C but <=39 degree C Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	7 / 116 (6.03%)	4 / 119 (3.36%)	0 / 138 (0.00%)	0 / 139 (0.00%)	6 / 78 (7.69%)	10 / 61 (16.39%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	7	4	0	0	6	10	0	0
Fever >39 degrees C but <=40 degrees C Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	1 / 115 (0.87%)	0 / 119 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 76 (0.00%)	3 / 58 (5.17%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	3	0	0
Decreased appetite Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	47 / 120 (39.17%)	44 / 129 (34.11%)	0 / 138 (0.00%)	0 / 139 (0.00%)	36 / 92 (39.13%)	30 / 68 (44.12%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	47	44	0	0	36	30	0	0
Irritability Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	98 / 128 (76.56%)	100 / 135 (74.07%)	0 / 138 (0.00%)	0 / 139 (0.00%)	72 / 97 (74.23%)	61 / 80 (76.25%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	98	100	0	0	72	61	0	0
Increased sleep Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	90 / 129 (69.77%)	86 / 129 (66.67%)	0 / 138 (0.00%)	0 / 139 (0.00%)	34 / 88 (38.64%)	29 / 71 (40.85%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	90	86	0	0	34	29	0	0
Decreased sleep Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	39 / 119 (32.77%)	42 / 124 (33.87%)	0 / 138 (0.00%)	0 / 139 (0.00%)	26 / 81 (32.10%)	30 / 67 (44.78%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	39	42	0	0	26	30	0	0
Fever >=38 degrees C but <=39 degrees C Infant Series Dose 2
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	3 / 96 (3.13%)	4 / 88 (4.55%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	3	4	0	0	0	0	0	0
Fever >40 degrees C Infant Series Dose 2
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[8]	2 / 96 (2.08%)	0 / 88 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Decreased appetite Infant Series Dose 2
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[9]	37 / 104 (35.58%)	37 / 98 (37.76%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	37	37	0	0	0	0	0	0
Irritability Infant Series Dose 2
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[10]	84 / 117 (71.79%)	96 / 119 (80.67%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	84	96	0	0	0	0	0	0
Increased sleep Infant Series Dose 2
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[11]	59 / 114 (51.75%)	62 / 109 (56.88%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	59	62	0	0	0	0	0	0
Decreased sleep Infant Series Dose 2
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[12]	35 / 98 (35.71%)	38 / 100 (38.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	35	38	0	0	0	0	0	0
Immune system disorders
Food allergy
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Drug hypersensitivity
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	3 / 139 (2.16%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	1 / 139 (0.72%)
occurrences all number	0	0	0	3	0	0	0	1
Cough
subjects affected / exposed	29 / 138 (21.01%)	16 / 139 (11.51%)	1 / 138 (0.72%)	0 / 139 (0.00%)	10 / 130 (7.69%)	10 / 122 (8.20%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	32	17	1	0	10	11	0	0
Rhinorrhoea
subjects affected / exposed	1 / 138 (0.72%)	7 / 139 (5.04%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	7	0	0	1	1	0	0
Wheezing
subjects affected / exposed	1 / 138 (0.72%)	2 / 139 (1.44%)	1 / 138 (0.72%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	3	1	0	1	0	0	0
Nasal congestion
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Sneezing
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Pharyngolaryngeal pain
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Dysphonia
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Grunting
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Psychiatric disorders
Crying
subjects affected / exposed	2 / 138 (1.45%)	4 / 139 (2.88%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	4	4	0	0	1	0	0	0
Insomnia
subjects affected / exposed	1 / 138 (0.72%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0
Agitation
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Restlessness
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Staring
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Investigations
Physical examination abnormal
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Cardiac murmur
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0
Radius fracture
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Head injury
subjects affected / exposed	2 / 138 (1.45%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Traumatic haematoma
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Congenital, familial and genetic disorders
Dacryostenosis congenital
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Lymphangioma
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Cardiac disorders
Cyanosis
subjects affected / exposed	2 / 138 (1.45%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Nervous system disorders
High-pitched crying
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Somnolence
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Hypertonia
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Lethargy
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Tympanic membrane perforation
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	7 / 138 (5.07%)	13 / 139 (9.35%)	0 / 138 (0.00%)	0 / 139 (0.00%)	3 / 130 (2.31%)	4 / 122 (3.28%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	7	13	0	0	3	5	0	0
Eye discharge
subjects affected / exposed	5 / 138 (3.62%)	3 / 139 (2.16%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	6	3	0	0	0	0	0	0
Ocular hyperaemia
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Astigmatism
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Dacryostenosis acquired
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Hypermetropia
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	24 / 138 (17.39%)	17 / 139 (12.23%)	0 / 138 (0.00%)	0 / 139 (0.00%)	12 / 130 (9.23%)	13 / 122 (10.66%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	32	17	0	0	14	14	0	0
Vomiting
subjects affected / exposed	19 / 138 (13.77%)	11 / 139 (7.91%)	0 / 138 (0.00%)	0 / 139 (0.00%)	12 / 130 (9.23%)	13 / 122 (10.66%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	25	12	0	0	13	14	0	0
Teething
subjects affected / exposed	11 / 138 (7.97%)	9 / 139 (6.47%)	0 / 138 (0.00%)	0 / 139 (0.00%)	4 / 130 (3.08%)	3 / 122 (2.46%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	12	9	0	0	4	3	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	5 / 138 (3.62%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	5	2	0	0	0	0	0	0
Constipation
subjects affected / exposed	1 / 138 (0.72%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0
Infantile spitting up
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0
Stomach discomfort
subjects affected / exposed	2 / 138 (1.45%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Abdominal discomfort
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Frequent bowel movements
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Reflux oesophagitis
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	11 / 138 (7.97%)	5 / 139 (3.60%)	1 / 138 (0.72%)	2 / 139 (1.44%)	1 / 130 (0.77%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	13	6	1	2	1	1	0	0
Rash
subjects affected / exposed	3 / 138 (2.17%)	5 / 139 (3.60%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	3	5	0	0	0	1	0	0
Dermatitis diaper
subjects affected / exposed	2 / 138 (1.45%)	5 / 139 (3.60%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	7	0	0	1	0	0	0
Dry skin
subjects affected / exposed	2 / 138 (1.45%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	3	0	0	0	0	0	0
Dermatitis atopic
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Dermatitis allergic
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Seborrhoeic dermatitis
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
Eczema infantile
subjects affected / exposed	1 / 138 (0.72%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 138 (0.00%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0
Urticaria
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Heat rash
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Rash erythematous
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Rash papular
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Skin discolouration
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Umbilical erythema
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Tenderness (Any) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[13]	55 / 123 (44.72%)	55 / 127 (43.31%)	0 / 138 (0.00%)	0 / 139 (0.00%)	39 / 87 (44.83%)	36 / 71 (50.70%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	55	55	0	0	39	36	0	0
Tenderness (Significant) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[14]	2 / 116 (1.72%)	8 / 122 (6.56%)	0 / 138 (0.00%)	0 / 139 (0.00%)	3 / 77 (3.90%)	2 / 58 (3.45%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	8	0	0	3	2	0	0
Induration (Any) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[15]	30 / 121 (24.79%)	37 / 126 (29.37%)	0 / 138 (0.00%)	0 / 139 (0.00%)	25 / 83 (30.12%)	27 / 68 (39.71%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	30	37	0	0	25	27	0	0
Induration (Mild) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[16]	26 / 120 (21.67%)	34 / 125 (27.20%)	0 / 138 (0.00%)	0 / 139 (0.00%)	23 / 82 (28.05%)	23 / 66 (34.85%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	26	34	0	0	23	23	0	0
Induration (Moderate) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[17]	8 / 118 (6.78%)	8 / 121 (6.61%)	0 / 138 (0.00%)	0 / 139 (0.00%)	3 / 77 (3.90%)	7 / 60 (11.67%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	8	8	0	0	3	7	0	0
Erythema (Any) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[18]	27 / 122 (22.13%)	50 / 126 (39.68%)	0 / 138 (0.00%)	0 / 139 (0.00%)	33 / 85 (38.82%)	39 / 73 (53.42%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	27	50	0	0	33	39	0	0
Erythema (Mild) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[19]	26 / 122 (21.31%)	50 / 126 (39.68%)	0 / 138 (0.00%)	0 / 139 (0.00%)	28 / 83 (33.73%)	35 / 71 (49.30%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	26	50	0	0	28	35	0	0
Erythema (Moderate) Infant Series Dose 1 and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[20]	2 / 116 (1.72%)	0 / 119 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	10 / 78 (12.82%)	10 / 61 (16.39%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	10	10	0	0
Tenderness (Any) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[21]	48 / 114 (42.11%)	39 / 96 (40.63%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	48	39	0	0	0	0	0	0
Tenderness (Significant) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: l 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[22]	4 / 97 (4.12%)	4 / 89 (4.49%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	4	4	0	0	0	0	0	0
Induration (Any) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[23]	32 / 106 (30.19%)	32 / 93 (34.41%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	32	32	0	0	0	0	0	0
Induration (Mild) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[24]	30 / 105 (28.57%)	27 / 93 (29.03%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	30	27	0	0	0	0	0	0
Induration (Moderate) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[25]	8 / 98 (8.16%)	6 / 88 (6.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	8	6	0	0	0	0	0	0
Induration (Severe) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[26]	1 / 96 (1.04%)	0 / 88 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Erythema (Any) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[27]	42 / 107 (39.25%)	40 / 99 (40.40%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	42	40	0	0	0	0	0	0
Erythema (Mild) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[28]	40 / 106 (37.74%)	37 / 99 (37.37%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	40	37	0	0	0	0	0	0
Erythema (Moderate) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[29]	4 / 98 (4.08%)	3 / 88 (3.41%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	4	3	0	0	0	0	0	0
Erythema (Severe) Infant Series Dose 2
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[30]	2 / 97 (2.06%)	0 / 88 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Infections and infestations
Rhinitis
subjects affected / exposed	32 / 138 (23.19%)	26 / 139 (18.71%)	1 / 138 (0.72%)	0 / 139 (0.00%)	11 / 130 (8.46%)	10 / 122 (8.20%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	40	39	1	0	11	10	0	0
Upper respiratory tract infection
subjects affected / exposed	16 / 138 (11.59%)	19 / 139 (13.67%)	0 / 138 (0.00%)	1 / 139 (0.72%)	4 / 130 (3.08%)	4 / 122 (3.28%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	19	21	0	1	4	4	0	0
Otitis media
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	1 / 138 (0.72%)	1 / 139 (0.72%)	1 / 130 (0.77%)	2 / 122 (1.64%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	1	1	1	2	0	0
Bronchiolitis
subjects affected / exposed	0 / 138 (0.00%)	2 / 139 (1.44%)	0 / 138 (0.00%)	1 / 139 (0.72%)	1 / 130 (0.77%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	2	0	1	1	1	0	0
Nasopharyngitis
subjects affected / exposed	15 / 138 (10.87%)	14 / 139 (10.07%)	0 / 138 (0.00%)	1 / 139 (0.72%)	9 / 130 (6.92%)	8 / 122 (6.56%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	18	19	0	1	9	9	0	0
Rubella
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	7 / 138 (5.07%)	4 / 139 (2.88%)	0 / 138 (0.00%)	0 / 139 (0.00%)	8 / 130 (6.15%)	2 / 122 (1.64%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	8	5	0	0	8	2	0	0
Varicella
subjects affected / exposed	2 / 138 (1.45%)	8 / 139 (5.76%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	8	0	0	1	0	0	0
Gastroenteritis
subjects affected / exposed	5 / 138 (3.62%)	4 / 139 (2.88%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	6	4	0	0	0	1	0	0
Oral candidiasis
subjects affected / exposed	5 / 138 (3.62%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	5	2	0	0	0	1	0	0
Viral infection
subjects affected / exposed	4 / 138 (2.90%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	2 / 130 (1.54%)	2 / 122 (1.64%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	4	2	0	0	2	2	0	0
Herpes zoster
subjects affected / exposed	2 / 138 (1.45%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	2	0	0	0	0	0	0
Injection site infection
subjects affected / exposed	1 / 138 (0.72%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0
Viral skin infection
subjects affected / exposed	2 / 138 (1.45%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 138 (0.00%)	2 / 139 (1.44%)	0 / 138 (0.00%)	0 / 139 (0.00%)	5 / 130 (3.85%)	3 / 122 (2.46%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	2	0	0	5	4	0	0
Eczema infected
subjects affected / exposed	2 / 138 (1.45%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Candidiasis
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Dermatitis infected
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Impetigo
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	2 / 130 (1.54%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0
Respiratory tract infection
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Skin candida
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Tonsillitis
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0
Bronchitis
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Eye infection
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Pharyngitis
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	1 / 122 (0.82%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Skin infection
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	2 / 122 (1.64%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 138 (0.72%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	1	0	0	1	0	0	0
Anorexia
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Increased appetite
subjects affected / exposed	0 / 138 (0.00%)	1 / 139 (0.72%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Weight gain poor
subjects affected / exposed	1 / 138 (0.72%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 130 (0.00%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Lactose intolerance
subjects affected / exposed	0 / 138 (0.00%)	0 / 139 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)	1 / 130 (0.77%)	0 / 122 (0.00%)	0 / 138 (0.00%)	0 / 139 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0

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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[16] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[17] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[18] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[19] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[20] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[21] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[22] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[23] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[24] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[25] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[26] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[27] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[28] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[29] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[30] - 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: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.

More information

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Were there any global substantial amendments to the protocol? Yes

09 Jul 2007

An amendment was made to change the medical monitor and to decrease the sample size from 600 to a minimum of 250 subjects in order to reach a target enrollment number within a reasonable time frame. Because the sample size was decreased, the statistical approach was changed from non-inferiority testing with regard to concomitant vaccine immunogenicity to descriptive statistics with a given level of precision. Given the level of precision for the immunogenicity assessments, the amended protocol will provide important information on the use of 13vPnC in the United Kingdom schedule to support licensure and provide information to vaccine recommending bodies.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Randomized, Active-Controlled, Double-blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Pediatric Vaccinations in the United Kingdom

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving a Meningococcal C Serum Bactericidal Assay (SBA) Titer >=1:8 and Predefined Antibody Levels for Pertussis and Haemophilus influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series.

Primary: Percentage of Subjects Achieving a Meningococcal C Serum Bactericidal Assay (SBA) Titer >=1:8 and Predefined Antibody Levels for Pertussis and Haemophilus influenzae Type b in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series.

Primary: Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Primary: Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Primary: Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Primary: Geometric Mean Antibody Concentration of Haemophilus Influenzae Type b (Hib) Polyribosylribitol Phosphate (PRP) as Measured by Enzyme-linked Immunosorbent Assay (ELISA) in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Primary: Geometric Mean Antibody Concentration of Pertusis Filamentous Haemagglutinin (FHA), Pertussis Toxoid (PT), Pertactin (PRN), and Fimbrial Agglutinogens (FIM) as Measured by ELISA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Primary: Geometric Mean Antibody Concentration of Pertusis Filamentous Haemagglutinin (FHA), Pertussis Toxoid (PT), Pertactin (PRN), and Fimbrial Agglutinogens (FIM) as Measured by ELISA in 13vPnC Group Relative to 7vPnC Group After the 2-dose Infant Series

Primary: Percentage of Subjects in the 13vPnC Group Achieving a Serotype-specific IgG Antibody Concentration >=0.35 mcg/mL Measured 1 Month After the 2-dose Infant Series, Before and After the Toddler Dose

Primary: Percentage of Subjects in the 13vPnC Group Achieving a Serotype-specific IgG Antibody Concentration >=0.35 mcg/mL Measured 1 Month After the 2-dose Infant Series, Before and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration in 13vPnC Group After the 2-dose Infant Series, Before and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration in 13vPnC Group After the 2-dose Infant Series, Before and After the Toddler Dose

Secondary: Percentage of Subjects Achieving an SBA Titer >=1:8 for Meningococcal C in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose

Secondary: Percentage of Subjects Achieving an SBA Titer >=1:8 for Meningococcal C in 13vPnC Group Relative to 7vPnC Group Before and After the Toddler Dose

Secondary: Percentage of Subjects Achieving a Predefined Antibody Level for Haemophilus Influenzae Type b in the 13vPnC Group Relative to the 7vPnC Group After the Toddler Dose

Secondary: Percentage of Subjects Achieving a Predefined Antibody Level for Haemophilus Influenzae Type b in the 13vPnC Group Relative to the 7vPnC Group After the Toddler Dose

Secondary: Geometric Mean Antibody Concentration for Haemophilus Influenzae Type b PRP in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

Secondary: Geometric Mean Antibody Concentration for Haemophilus Influenzae Type b PRP in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

Secondary: Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

Secondary: Geometric Mean Titer (GMT) of Meningococcal C Antigen as Measured by SBA in 13vPnC Group Relative to 7vPnC Group After the Toddler Dose

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Randomized, Active-Controlled, Double-blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Pediatric Vaccinations in the United Kingdom