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 Given With DTaP Compared to Open-Label DTaP in Healthy Japanese Infants

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

Summary
EudraCT number	2014-004181-21
Trial protocol	Outside EU/EEA
Global end of trial date	30 Nov 2011

Results information
Results version number	v2(current)
This version publication date	29 Jul 2016
First version publication date	24 Jul 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set reporting periods and duplicate AEs in their data

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

6096A1-3024

ISRCTN number

US NCT number

NCT01200368

WHO universal trial number (UTN)

Other trial identifiers

Alias: B1851056

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)

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

07 Mar 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 Nov 2011

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that the immune responses to the 13 pneumococcal conjugates (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) induced by 13-valent pneumococcal conjugate vaccine (13vPnC) are non-inferior to the immune responses induced by 7-valent pneumococcal conjugate vaccine (7vPnC) when measured 1 month after the infant series. To assess whether the immune responses as measured by serum antibody responses to diphtheria toxoid, tetanus toxoid, pertussis toxoid (PT), and filamentous hemagglutinin (FHA) induced by diphtheria, tetanus, and acellular pertussis vaccine (DTaP) given with 13vPnC are comparable to the immune responses induced by DTaP given alone when measured 1 month after the infant series. To evaluate the acceptability of the safety profile of 13vPnC and 7vPnC given with DTaP as measured by the incidence rates of local reactions, systemic events, and adverse events(AEs).

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

24 Sep 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 551

Worldwide total number of subjects

551

EEA total number of subjects

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)

551

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Study conducted in Japan from 24 September 2010 to 30 November 2011. Total 551 subjects were enrolled and randomized in three groups (13vPnC+DTaP, 7vPnC+DTaP and DTaP [Catch-up 7vPnC]) however only 549 were vaccinated. Two subjects were randomized to DTaP (Catch-up 7vPnC) and 7vPnC+DTaP respectively, but never vaccinated.

Period 1 title

Infant Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC + DTaP Infant Series

Arm description

Subjects at 3 to 6 months of age received a single dose of 13vPnC subcutaneously followed by 2 single doses of 13vPnC subcutaneously, 4 to 8 weeks after each previous dose (infant series). A single dose of DTaP subcutaneously administered concomitantly with each 13vPnC dose.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects at 3 to 6 months of age received a single 0.5 milliliter (mL) dose of 13vPnC subcutaneously followed by 2 single 0.5 mL doses of 13vPnC subcutaneously, 4 to 8 weeks after each previous dose (infant series).

Investigational medicinal product name

DTaP

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received a single 0.5 mL dose of DTaP subcutaneously concomitantly with each 13vPnC dose.

7vPnC + DTaP Infant Series

Arm description

Subjects at 3 to 6 months of age received a single dose of 7vPnC subcutaneously followed by 2 single doses of 7vPnC subcutaneously 4 to 8 weeks after each previous dose (infant series). A single dose of DTaP subcutaneously administered concomitantly with each 7vPnC dose.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects at 3 to 6 months of age received a single 0.5 mL dose of 7vPnC subcutaneously followed by 2 single 0.5 mL doses of 7vPnC subcutaneously, 4 to 8 weeks after each previous dose (infant series).

Investigational medicinal product name

DTaP

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received a single 0.5 mL dose of DTaP subcutaneously concomitantly with each 7vPnC dose.

DTaP (Catch-up 7vPnC) Infant Series

Arm description

Subjects at 3 to 6 months of age received a single DTaP dose subcutaneously followed by 2 single DTaP doses subcutaneously, 4 to 8 weeks after each previous dose (infant series).

Arm type

Active comparator

Investigational medicinal product name

DTaP

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects at 3 to 6 months of age received a single 0.5 mL DTaP dose subcutaneously followed by 2 single 0.5 mL DTaP doses subcutaneously, 4 to 8 weeks after each previous dose (infant series).

Number of subjects in period 1	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Started	183	184	184
Vaccinated Dose 1	183	183	183
Vaccinated Dose 2	183	182	183
Vaccinated Dose 3	181	178	182
Completed	180	178	178
Not completed	3	6	6
Consent withdrawn by subject	-	2	2
Did not meet entrance criteria	-	1	-
Adverse Event	2	2	3
Unspecified	1	-	-
Randomized, not vaccinated	-	1	1

Period 2 title

After Infant Series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC + DTaP After Infant Series

Arm description

Included subjects who received a single dose of 13vPnC at 3 to 6 months of age subcutaneously followed by 2 single doses of 13vPnC subcutaneously, 4 to 8 weeks after each previous dose (infant series). A single dose of DTaP subcutaneously administered concomitantly with each 13vPnC dose.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

7vPnC + DTaP After Infant Series

Arm description

Included subjects who received a single dose of 7vPnC at 3 to 6 months of age subcutaneously followed by 2 single doses of 7vPnC subcutaneously 4 to 8 weeks after each previous dose (infant series). A single dose of DTaP subcutaneously administered concomitantly with each 7vPnC dose.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

DTaP (Catch-up 7vPnC) After Infant Series

Arm description

Included subjects who received 4 to 6 weeks post-infant series, 2 single catch-up (CU) doses of 7vPnC (Prevenar) were administered subcutaneously, 4 to 6 weeks apart.

Arm type

Active comparator

Investigational medicinal product name

7vPnC (CU)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received 2 single CU doses of 7vPnC (Prevenar) were administered subcutaneously, 4 to 6 weeks apart.

Number of subjects in period 2	13vPnC + DTaP After Infant Series	7vPnC + DTaP After Infant Series	DTaP (Catch-up 7vPnC) After Infant Series
Started	180	178	178
Completed	162	162	169
Not completed	18	16	9
Consent withdrawn by subject	10	8	4
Adverse Event	6	6	3
Unspecified	1	2	2
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

Subject, Investigator, Monitor, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC + DTaP Toddler Series

Arm description

Subjects received a single dose of 13vPnC subcutaneously at 12 to 15 months of age (toddler dose). A single dose of DTaP subcutaneously administered concomitantly with each 13vPnC dose.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received a single 0.5 mL dose of 13vPnC subcutaneously at 12 to 15 months of age (toddler dose).

Investigational medicinal product name

DTaP

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received a single 0.5 mL dose of DTaP subcutaneously concomitantly with each 13vPnC dose.

7vPnC + DTaP Toddler Series

Arm description

Subjects received single dose of 7vPnC subcutaneously at 12 to 15 months of age (toddler dose). A single dose of DTaP subcutaneously administered concomitantly with each 7vPnC dose.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received single 0.5 mL dose of 7vPnC subcutaneously at 12 to 15 months of age (toddler dose).

Investigational medicinal product name

DTaP

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received a single 0.5 mL dose of DTaP subcutaneously concomitantly with each 7vPnC dose.

DTaP (Catch-up 7vPnC) Toddler Series

Arm description

Subjects received a single DTaP dose subcutaneously at 12 to 15 months of age (toddler dose) followed by a single CU dose of 7vPnC (Prevenar) subcutaneously 4 to 6 weeks post-toddler dose.

Arm type

Active comparator

Investigational medicinal product name

DTaP

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received a single 0.5 mL DTaP dose subcutaneously at 12 to 15 months of age (toddler dose).

Investigational medicinal product name

7vPnC (CU)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Subjects received 2 single CU doses of 7vPnC (Prevenar) were administered subcutaneously, 4 to 6 weeks post-toddler dose.

Number of subjects in period 3	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series	DTaP (Catch-up 7vPnC) Toddler Series
Started	162	162	169
Completed	162	159	168
Not completed	0	3	1
Adverse Event	-	3	1

Baseline characteristics

Top of page

Reporting group title

13vPnC + DTaP Infant Series

Reporting group description

Reporting group title

7vPnC + DTaP Infant Series

Reporting group description

Reporting group title

DTaP (Catch-up 7vPnC) Infant Series

Reporting group description

Subjects at 3 to 6 months of age received a single DTaP dose subcutaneously followed by 2 single DTaP doses subcutaneously, 4 to 8 weeks after each previous dose (infant series).

Reporting group values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series	Total
Number of subjects	183	184	184	551
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	4.1 ( 0.97 )	4.1 ( 0.97 )	4.2 ( 0.96 )	-
Gender categorical
Units: Subjects
Female	87	91	91	269
Male	96	93	93	282

End points

Top of page

Reporting group title

13vPnC + DTaP Infant Series

Reporting group description

Reporting group title

7vPnC + DTaP Infant Series

Reporting group description

Reporting group title

DTaP (Catch-up 7vPnC) Infant Series

Reporting group description

Subjects at 3 to 6 months of age received a single DTaP dose subcutaneously followed by 2 single DTaP doses subcutaneously, 4 to 8 weeks after each previous dose (infant series).

Reporting group title

13vPnC + DTaP After Infant Series

Reporting group description

Reporting group title

7vPnC + DTaP After Infant Series

Reporting group description

Reporting group title

DTaP (Catch-up 7vPnC) After Infant Series

Reporting group description

Included subjects who received 4 to 6 weeks post-infant series, 2 single catch-up (CU) doses of 7vPnC (Prevenar) were administered subcutaneously, 4 to 6 weeks apart.

Reporting group title

13vPnC + DTaP Toddler Series

Reporting group description

Subjects received a single dose of 13vPnC subcutaneously at 12 to 15 months of age (toddler dose). A single dose of DTaP subcutaneously administered concomitantly with each 13vPnC dose.

Reporting group title

7vPnC + DTaP Toddler Series

Reporting group description

Subjects received single dose of 7vPnC subcutaneously at 12 to 15 months of age (toddler dose). A single dose of DTaP subcutaneously administered concomitantly with each 7vPnC dose.

Reporting group title

DTaP (Catch-up 7vPnC) Toddler Series

Reporting group description

Subjects received a single DTaP dose subcutaneously at 12 to 15 months of age (toddler dose) followed by a single CU dose of 7vPnC (Prevenar) subcutaneously 4 to 6 weeks post-toddler dose.

Primary: Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Microgram Per Milliliter (mcg/mL) 1 Month After the Infant Series

Top of page

End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Microgram Per Milliliter (mcg/mL) 1 Month After the Infant Series ^[1]

End point description

Percentage of subjects achieving predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95 percentage (%) confidence interval (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. Exact 2-sided CI based on the observed proportion of subjects. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest response observed among the 7 common serotypes in the group was taken as reference. Evaluable infant immunogenicity population: eligible subjects who received the vaccine to which they were randomized at all 3 doses, had blood drawn within the protocol-specified time frames, had at least 1 valid and determinate assay result after Dose 3 for the proposed analysis, and had no major protocol violations.

End point type

Primary

End point timeframe

1 month after the infant series

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for these two reporting arms ( 13vPnC + DTaP Infant Series and 7vPnC + DTaP Infant Series) only.

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series
Number of subjects analysed	177	176
Units: Percentage of Subjects
number (confidence interval 95%)
Serotype 4	100 (97.9 to 100)	100 (97.9 to 100)
Serotype 6B	97.7 (94.3 to 99.4)	99.4 (96.9 to 100)
Serotype 9V	100 (97.9 to 100)	100 (97.9 to 100)
Serotype 14	100 (97.9 to 100)	100 (97.9 to 100)
Serotype 18C	100 (97.9 to 100)	100 (97.9 to 100)
Serotype 19F	98.9 (96 to 99.9)	96.6 (92.7 to 98.7)
Serotype 23F	97.7 (94.3 to 99.4)	98.3 (95.1 to 99.6)
Serotype 1	100 (97.9 to 100)	96.6 (92.7 to 98.7)
Serotype 3	99.4 (96.9 to 100)	96.6 (92.7 to 98.7)
Serotype 5	99.4 (96.9 to 100)	96.6 (92.7 to 98.7)
Serotype 6A	98.3 (95.1 to 99.6)	96.6 (92.7 to 98.7)
Serotype 7F	100 (97.9 to 100)	96.6 (92.7 to 98.7)
Serotype 19A	100 (97.9 to 100)	96.6 (92.7 to 98.7)

Serotype 4

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

2.1

Notes
[2] - Non-inferiority was declared if the lower confidence interval for the percent difference was greater than (>) -0.10.

Serotype 6B

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Percent difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

1.1

Notes
[3] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 9V

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.1

Notes
[4] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 14

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.1

Notes
[5] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 18C

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.1

Notes
[6] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 19F

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Percent difference

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

6.3

Notes
[7] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 23F

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Percent difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

2.9

Notes
[8] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 1

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI. Difference in proportions was calculated using the serotype with the lowest proportion among the 7 common serotypes in the 7vPnC + DTaP group as reference.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

Percent difference

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

7.3

Notes
[9] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 3

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Percent difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

6.7

Notes
[10] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 5

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

Percent difference

Point estimate

2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

6.7

Notes
[11] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

Percent difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

5.8

Notes
[12] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

Method

Parameter type

Percent difference

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

7.3

Notes
[13] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

Parameter type

Percent difference

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

7.3

Notes
[14] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Primary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 7 Common Serotypes 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 7 Common Serotypes 1 Month After the Infant Series ^[15]

End point description

Antibody geometric mean concentration (GMC) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) are presented. GMC (13vPnC) and corresponding 2-sided 95% CI were evaluated. Geometric means (GMs) were calculated using all subjects with available data for the specified blood draw. Evaluable infant immunogenicity population: eligible subjects who received the vaccine to which they were randomized at all 3 doses, had blood drawn within the protocol-specified time frames, had at least 1 valid and determinate assay result after Dose 3 for the proposed analysis, and had no major protocol violations.

End point type

Primary

End point timeframe

1 month after the infant series

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for these two reporting arms ( 13vPnC + DTaP Infant Series and 7vPnC + DTaP Infant Series) only.

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series
Number of subjects analysed	177	176
Units: mcg/mL
geometric mean (confidence interval 95%)
Serotype 4	9.4 (8.48 to 10.41)	11.54 (10.51 to 12.67)
Serotype 6B	4.5 (3.9 to 5.21)	5.71 (4.93 to 6.63)
Serotype 9V	5.04 (4.52 to 5.62)	6.8 (6.15 to 7.52)
Serotype 14	13.86 (12.16 to 15.8)	16.79 (15.03 to 18.76)
Serotype 18C	5.3 (4.75 to 5.91)	7.26 (6.53 to 8.08)
Serotype 19F	7.37 (6.43 to 8.46)	8.38 (7.17 to 9.8)
Serotype 23F	3.64 (3.16 to 4.19)	4.53 (3.96 to 5.18)

Serotype 4

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

Parameter type

GMC ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.94

Notes
[16] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for the IgG GMC ratio was >0.5.

Serotype 6B

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

Method

Parameter type

GMC ratio

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.97

Notes
[17] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 9V

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

GMC ratio

Point estimate

0.74

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.86

Notes
[18] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 14

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

Parameter type

GMC ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.98

Notes
[19] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 18C

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

Parameter type

GMC ratio

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.85

Notes
[20] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 19F

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

GMC ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.08

Notes
[21] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 23F

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

GMC ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

0.98

Notes
[22] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Primary: Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Infant Series

Top of page

End point title

Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Infant Series

End point description

Predefined antibody levels were 0.1 International Units/mL (IU/mL) for diphtheria, 0.01 IU/mL for tetanus, 5 Enzyme-linked Immunosorbent Assay (ELISA) units/mL (EU/mL) for pertussis toxoid (PT), and 5 EU/mL for filamentous hemagglutinin (FHA). Evaluable infant immunogenicity population: eligible subjects who received the vaccine to which they were randomized at all 3 doses, had blood drawn within the protocol-specified time frames, had at least 1 valid and determinate assay result after Dose 3 for the proposed analysis, and had no major protocol violations.

End point type

Primary

End point timeframe

1 month after the infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	177	176	175
Units: Percentage of subjects
number (confidence interval 95%)
Diphtheria	99.4 (96.9 to 100)	96.6 (92.7 to 98.7)	100 (97.9 to 100)
Tetanus	100 (97.9 to 100)	100 (97.9 to 100)	100 (97.9 to 100)
Pertussis toxoid (PT)	99.4 (96.9 to 100)	96.6 (92.7 to 98.7)	100 (97.9 to 100)
Filamentous hemagglutinin (FHA)	99.4 (96.9 to 100)	96.6 (92.7 to 98.7)	100 (97.9 to 100)

Difference in percentage for diphtheria toxoid

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for diphtheria toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

DTaP (Catch-up 7vPnC) Infant Series v 13vPnC + DTaP Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

other ^[23]

Method

Parameter type

Percent difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

1.6

Notes
[23] - The DTap response was summarized by descriptive.

Difference in percentage for tetanus toxoid

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for tetanus toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

other ^[24]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

2.2

Notes
[24] - The DTap response was summarized by descriptive.

Difference in percentage for PT

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for pertussis toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

other ^[25]

Method

Parameter type

Percent difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

1.6

Notes
[25] - The DTap response was summarized by descriptive.

Difference in percentage for FHA

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for filamentous hemagglutinin and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

other ^[26]

Method

Parameter type

Percent difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

1.6

Notes
[26] - The DTap response was summarized by descriptive.

Secondary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 6 Additional Serotypes 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 6 Additional Serotypes 1 Month After the Infant Series ^[27]

End point description

Antibody GMC for 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were evaluated. GMs were calculated using all subjects with available data for the specified blood draw. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest GMC observed among the 7 common serotypes in the group was taken as reference. Evaluable infant immunogenicity population: eligible subjects who received the vaccine to which they were randomized at all 3 doses, had blood drawn within the protocol-specified time frames, had at least 1 valid and determinate assay result after Dose 3 for the proposed analysis, and had no major protocol violations.

End point type

Secondary

End point timeframe

1 month after the infant series

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be analyzed for these two reporting arms ( 13vPnC + DTaP Infant Series and 7vPnC + DTaP Infant Series) only.

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series
Number of subjects analysed	177	176
Units: mcg/mL
geometric mean (confidence interval 95%)
Serotype 1	8.14 (7.23 to 9.18)	4.53 (3.96 to 5.18)
Serotype 3	4.9 (4.43 to 5.42)	4.53 (3.96 to 5.18)
Serotype 5	4.64 (4.14 to 5.2)	4.53 (3.96 to 5.18)
Serotype 6A	4.71 (4.15 to 5.34)	4.53 (3.96 to 5.18)
Serotype 7F	8.26 (7.45 to 9.17)	4.53 (3.96 to 5.18)
Serotype 19A	8.56 (7.67 to 9.56)	4.53 (3.96 to 5.18)

Serotype 1

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI. GMC ratio was calculated using the serotype with the lowest GMC among the 7 common serotypes in the 7vPnC + DTaP group as reference.

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

Method

Parameter type

GMC ratio

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.5

upper limit

2.15

Notes
[28] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 3

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

GMC ratio

Point estimate

1.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.28

Notes
[29] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 5

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

GMC ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.22

Notes
[30] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

Method

Parameter type

GMC ratio

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.25

Notes
[31] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

Method

Parameter type

GMC ratio

Point estimate

1.83

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

2.16

Notes
[32] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC + DTaP Infant Series v 7vPnC + DTaP Infant Series

Number of subjects included in analysis

353

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

Method

Parameter type

GMC ratio

Point estimate

1.89

Confidence interval

level

95%

sides

2-sided

lower limit

1.59

upper limit

2.25

Notes
[33] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level >=0.35 mcg/mL 1 Month After the Toddler Dose

Top of page

End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level >=0.35 mcg/mL 1 Month After the Toddler Dose

End point description

Percentage of subjects achieving 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. Exact 2-sided CI based on the observed proportion of subjects. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest response observed among the 7 common serotypes in the group was taken as reference. Evaluable toddler immunogenicity set:eligible subjects who received vaccine to which they were randomized at all 4 doses,had blood drawn within specified time,had >=1 valid assay result after toddler dose for analysis,had no major protocol violation.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series
Number of subjects analysed	158 ^[34]	154 ^[35]
Units: Percentage of subjects
number (confidence interval 95%)
Serotype 4	100 (97.7 to 100)	100 (97.6 to 100)
Serotype 6B	100 (97.7 to 100)	100 (97.6 to 100)
Serotype 9V	100 (97.7 to 100)	100 (97.6 to 100)
Serotype 14	100 (97.7 to 100)	100 (97.6 to 100)
Serotype 18C	100 (97.7 to 100)	100 (97.6 to 100)
Serotype 19F	98.7 (95.5 to 99.8)	99.4 (96.4 to 100)
Serotype 23F	100 (97.7 to 100)	100 (97.6 to 100)
Serotype 1	99.4 (96.5 to 100)	99.4 (96.4 to 100)
Serotype 3	99.4 (96.5 to 100)	99.4 (96.4 to 100)
Serotype 5	100 (97.7 to 100)	99.4 (96.4 to 100)
Serotype 6A	100 (97.7 to 100)	99.4 (96.4 to 100)
Serotype 7F	100 (97.7 to 100)	99.4 (96.4 to 100)
Serotype 19A	100 (97.7 to 100)	99.4 (96.4 to 100)

Notes
[34] - Subjects with determinate IgG antibody level to serotype.
[35] - Subjects with determinate IgG antibody level to serotype.

Serotype 4

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.4

Notes
[36] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 6B

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.4

Notes
[37] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 9V

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.4

Notes
[38] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 14

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[39]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.4

Notes
[39] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 18C

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.4

Notes
[40] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 19F

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

Method

Parameter type

Percent difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

2.4

Notes
[41] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 23F

Statistical analysis description

Difference ([13vPnC + DTaP] – [7vPnC + DTaP]) in proportions, expressed as a percentage presented along with exact 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.4

Notes
[42] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 1

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

Notes
[43] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 3

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

Notes
[44] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 5

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

Method

Parameter type

Percent difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

3.6

Notes
[45] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

Method

Parameter type

Percent difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

3.6

Notes
[46] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

Method

Parameter type

Percent difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

3.6

Notes
[47] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

Method

Parameter type

Percent difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

3.6

Notes
[48] - Non-inferiority was declared if the lower confidence interval for the percent difference was >-0.10.

Secondary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

End point description

Antibody GMC as measured by mcg/mL 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. GMC (13vPnC) and corresponding 2-sided 95% confidence intervals (CI) were evaluated. Geometric means (GMs) were calculated using all subjects with available data for the specified blood draw. To demonstrate non-inferiority, for 6 additional serotypes in 7vPnC + DTaP group, the lowest GMC observed among the 7 common serotypes in the group was taken as reference. Evaluable toddler immunogenicity set:eligible subjects who received vaccine to which they were randomized at all 4 doses,had blood drawn within specified time,had >=1 valid assay result after toddler dose for analysis,had no major protocol violation.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series
Number of subjects analysed	158 ^[49]	154 ^[50]
Units: mcg/mL
geometric mean (confidence interval 95%)
Serotype 4	15.34 (13.23 to 17.79)	16.35 (14.19 to 18.83)
Serotype 6B	17.05 (14.47 to 20.08)	13.91 (11.93 to 16.21)
Serotype 9V	7 (6.11 to 8.03)	8.64 (7.54 to 9.89)
Serotype 14	19.7 (17.69 to 21.93)	20.69 (18.25 to 23.47)
Serotype 18C	8.1 (6.94 to 9.47)	9.88 (8.64 to 11.3)
Serotype 19F	16.73 (14.2 to 19.71)	9.55 (8.11 to 11.26)
Serotype 23F	8.64 (7.46 to 10.01)	10 (8.61 to 11.62)
Serotype 1	13.96 (11.94 to 16.31)	8.64 (7.54 to 9.89)
Serotype 3	2.48 (2.17 to 2.85)	8.64 (7.54 to 9.89)
Serotype 5	11.1 (9.83 to 12.53)	8.64 (7.54 to 9.89)
Serotype 6A	15.17 (13.31 to 17.3)	8.64 (7.54 to 9.89)
Serotype 7F	10.9 (9.54 to 12.45)	8.64 (7.54 to 9.89)
Serotype 19A	16.02 (14.07 to 18.25)	8.64 (7.54 to 9.89)

Notes
[49] - Subjects with determinate IgG antibody level to serotype.
[50] - Subjects with determinate IgG antibody level to serotype.

Serotype 4

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

Method

Parameter type

GMC ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.15

Notes
[51] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 6B

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

Method

Parameter type

GMC ratio

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.98

upper limit

1.53

Notes
[52] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 9V

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

Method

Parameter type

GMC ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

0.98

Notes
[53] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 14

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

Method

Parameter type

GMC ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.12

Notes
[54] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 18C

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

Method

Parameter type

GMC ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.01

Notes
[55] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 19F

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

Method

Parameter type

GMC ratio

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

1.39

upper limit

2.21

Notes
[56] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 23F

Statistical analysis description

Ratio of IgG GMCs ([13vPnC + DTaP]/[7vPnC + DTaP]) was calculated along with 2-sided 95% CI.

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[57]

Method

Parameter type

GMC ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.07

Notes
[57] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 1

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[58]

Method

Parameter type

GMC ratio

Point estimate

1.62

Confidence interval

level

95%

sides

2-sided

lower limit

1.31

upper limit

1.99

Notes
[58] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 3

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[59]

Method

Parameter type

GMC ratio

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.24

upper limit

0.35

Notes
[59] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 5

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[60]

Method

Parameter type

GMC ratio

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

1.54

Notes
[60] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[61]

Method

Parameter type

GMC ratio

Point estimate

1.76

Confidence interval

level

95%

sides

2-sided

lower limit

1.46

upper limit

2.12

Notes
[61] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 7F

Statistical analysis description

Comparison groups

7vPnC + DTaP Toddler Series v 13vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[62]

Method

Parameter type

GMC ratio

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.52

Notes
[62] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC + DTaP Toddler Series v 7vPnC + DTaP Toddler Series

Number of subjects included in analysis

312

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[63]

Method

Parameter type

GMC ratio

Point estimate

1.85

Confidence interval

level

95%

sides

2-sided

lower limit

1.54

upper limit

2.24

Notes
[63] - Non-inferiority was declared if the lower limit of the 2-sided, 95% CI for IgG GMC ratio was >0.5.

Secondary: Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Toddler Dose

Top of page

End point title

Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Toddler Dose

End point description

Predefined antibody level was 0.1 IU/mL for diphtheria, 0.01 IU/mL for tetanus, 5 EU/mL for PT, and 5 EU/mL for FHA. Evaluable toddler immunogenicity population.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series	DTaP (Catch-up 7vPnC) Toddler Series
Number of subjects analysed	157 ^[64]	154 ^[65]	163 ^[66]
Units: Percentage of subjects
number (confidence interval 95%)
Diphtheria	100 (97.7 to 100)	100 (97.6 to 100)	100 (97.8 to 100)
Tetanus	100 (97.7 to 100)	100 (97.6 to 100)	100 (97.8 to 100)
Pertussis toxoid (PT)	100 (97.7 to 100)	100 (97.6 to 100)	100 (97.8 to 100)
Filamentous hemagglutinin (FHA)	100 (97.7 to 100)	100 (97.6 to 100)	100 (97.8 to 100)

Notes
[64] - Number of subjects with determinate DTaP antibody level to serotype.
[65] - Number of subjects with determinate DTaP antibody level to serotype.
[66] - Number of subjects with determinate DTaP antibody level to serotype.

Diphtheria toxoid

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for diphtheria toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other ^[67]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.3

Notes
[67] - The DTap response was summarized by descriptive.

Tetanus toxoid

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for tetanus toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other ^[68]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.3

Notes
[68] - The DTap response was summarized by descriptive.

Pertussis toxoid

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for pertussis toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other ^[69]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.3

Notes
[69] - The DTap response was summarized by descriptive.

Filamentous hemagglutinin

Statistical analysis description

Difference in percentage of subjects achieving predefined antibody levels for filamentous hemagglutinin and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other ^[70]

Method

Parameter type

Percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.3

Notes
[70] - The DTap response was summarized by descriptive.

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibodies 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibodies 1 Month After the Infant Series

End point description

GMC was measured in IU/mL and corresponding 2-sided 95% CI were evaluated for diphtheria and tetanus antibodies. Evaluable infant immunogenicity population: eligible subjects who received the vaccine to which they were randomized at all 3 doses, had blood drawn within the protocol-specified time frames, had at least 1 valid and determinate assay result for the proposed analysis, and had no major protocol violations.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	177	176	175
Units: IU/mL
geometric mean (confidence interval 95%)
Diphtheria	1.03 (0.94 to 1.12)	1.1 (0.97 to 1.25)	0.93 (0.86 to 1.02)
Tetanus	1.5 (1.31 to 1.7)	1.37 (1.17 to 1.6)	1.66 (1.5 to 1.83)

Diphtheria toxoid

Statistical analysis description

GMC ratio for diphtheria toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.24

Tetanus toxoid

Statistical analysis description

GMC ratio for tetanus toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.06

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibodies 1 Month After the Infant Series

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibodies 1 Month After the Infant Series

End point description

GMC was measured in EU/mL and corresponding 2-sided 95% CI were evaluated for PT and FHA antibodies. Evaluable infant immunogenicity population: eligible subjects who received the vaccine to which they were randomized at all expected doses, had blood drawn within the protocol-specified time frames, had at least 1 valid and determinate assay result for the proposed analysis, and had no major protocol violations.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	177	176	175
Units: EU/mL
geometric mean (confidence interval 95%)
PT	66.12 (60.45 to 72.32)	57.26 (49.23 to 66.6)	67.64 (62.87 to 72.78)
FHA	62.3 (56.59 to 68.59)	53.86 (47.27 to 61.37)	67.48 (61.64 to 73.86)

GMC for Pertusis Toxoid

Statistical analysis description

GMC ratio for PT and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.1

GMC for Filamentous hemagglutinin

Statistical analysis description

GMC ratio for FHA and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Infant Series v DTaP (Catch-up 7vPnC) Infant Series

Number of subjects included in analysis

352

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.05

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibody 1 Month After the Toddler Dose

End point description

GMC was measured in IU/mL and corresponding 2-sided 95% CI were evaluated for diphtheria and tetanus antibodies. Evaluable toddler immunogenicity population.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series	DTaP (Catch-up 7vPnC) Toddler Series
Number of subjects analysed	157 ^[71]	154 ^[72]	163 ^[73]
Units: IU/mL
geometric mean (confidence interval 95%)
Diphtheria	2.65 (2.43 to 2.9)	3.18 (2.94 to 3.45)	2.63 (2.39 to 2.91)
Tetanus	2.9 (2.56 to 3.28)	2.6 (2.29 to 2.95)	2.89 (2.58 to 3.25)

Notes
[71] - Number of subjects with determinate DTaP antibody level to serotype.
[72] - Number of subjects with determinate DTaP antibody level to serotype.
[73] - Number of subjects with determinate DTaP antibody level to serotype.

Diphtheria toxoid

Statistical analysis description

GMC ratio for diphtheria toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.15

Tetanus toxoid

Statistical analysis description

GMC ratio for tetanus toxoid and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.19

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibody 1 Month After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibody 1 Month After the Toddler Dose

End point description

GMC was measured in EU/mL and corresponding 2-sided 95% CI were evaluated for PT and FHA antibodies. Evaluable toddler immunogenicity population.

End point type

Secondary

End point timeframe

1 month after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series	DTaP (Catch-up 7vPnC) Toddler Series
Number of subjects analysed	157 ^[74]	154 ^[75]	163 ^[76]
Units: EU/mL
geometric mean (confidence interval 95%)
PT	144.46 (130.68 to 159.68)	135.65 (124.16 to 148.21)	150.21 (136.2 to 165.65)
FHA	143.68 (130.94 to 157.66)	141.19 (129.2 to 154.3)	180.31 (163.12 to 199.32)

Notes
[74] - Number of subjects with determinate DTaP antibody level to serotype.
[75] - Number of subjects with determinate DTaP antibody level to serotype.
[76] - Number of subjects with determinate DTaP antibody level to serotype.

GMC for Pertusis Toxoid

Statistical analysis description

GMC ratio for PT and corresponding 2-sided 95% CI were calculated.

Comparison groups

DTaP (Catch-up 7vPnC) Toddler Series v 13vPnC + DTaP Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.11

GMC for Filamentous hemagglutinin

Statistical analysis description

GMC ratio for FHA and corresponding 2-sided 95% CI were calculated.

Comparison groups

13vPnC + DTaP Toddler Series v DTaP (Catch-up 7vPnC) Toddler Series

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

GMC ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.91

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 1 (3 to 6 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 1 (3 to 6 Months of Age)

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). Redness and swelling were scaled as Any (redness or swelling 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. Safety population included all subjects who received at least 1 dose of study vaccine. 'n'=subjects reporting yes for at least 1 day or no for all days for the specified local reaction for each group, respectively.

End point type

Other pre-specified

End point timeframe

Within 7 days after Dose 1 of the infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	175 ^[77]	174 ^[78]	165 ^[79]
Units: Percentage of subjects
number (not applicable)
Redness- Any (n=171, 172, 165)	58.5	55.8	10.3
Redness- Mild (n=170, 172, 165)	48.2	51.2	10.3
Redness- Moderate (n=164, 166, 162)	18.9	18.1	0
Redness- Severe (n=161, 162, 162)	0	0.6	0
Swelling- Any (n=168, 168, 164)	41.1	35.7	4.9
Swelling- Mild (n= 168, 168, 164)	38.1	31.5	4.9
Swelling- Moderate (n=162, 165, 162)	12.3	12.7	0
Swelling- severe (n=161, 162, 162)	0	0.6	0
Tenderness- Any (n=163, 164, 162)	13.5	6.1	1.2
Tenderness- Significant (n=161, 162, 162)	0	0	0
Any local reaction (n=175, 174, 165)	68	60.9	12.1

Notes
[77] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[78] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[79] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 2 (4 to 8 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 2 (4 to 8 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 7 days after Dose 2 of the infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	167 ^[80]	173 ^[81]	164 ^[82]
Units: Percentage of subjects
number (not applicable)
Redness- Any (n= 166, 168, 161)	62.7	61.9	36.6
Redness- Mild (n= 166, 167, 161)	56	56.9	34.8
Redness- Moderate (n= 157, 159, 156)	26.1	27	8.3
Redness- Severe (n= 157, 154, 154)	0	0	0
Swelling- Any (n= 160, 171, 162)	48.1	50.9	24.1
Swelling- Mild (n= 160, 170, 162)	44.4	48.2	22.8
Swelling- Moderate (n= 157, 157, 155)	19.7	17.8	5.8
Swelling- severe (n= 157, 154, 154)	0	0	0
Tenderness- Any (n= 159, 154, 155)	14.5	4.5	1.9
Tenderness- Significant (n= 157, 154, 154)	0.6	0	0
Any local reaction (n=167, 173, 164)	71.3	67.1	40.2

Notes
[80] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[81] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[82] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 3 (5 to 10 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 3 (5 to 10 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 7 days after Dose 3 of the infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	171 ^[83]	163 ^[84]	160 ^[85]
Units: Percentage of subjects
number (not applicable)
Redness- Any (n= 168, 162, 156)	53.6	51.2	23.1
Redness- Mild (n= 167, 160, 156)	47.3	43.1	21.8
Redness- Moderate (n= 152, 154, 153)	17.1	22.1	2
Redness- Severe (n= 149, 152, 152)	0	0	0
Swelling- Any (n= 164, 157, 159)	43.9	37.6	21.4
Swelling- Mild (n= 164, 156, 159)	42.1	34	20.1
Swelling- Moderate (n= 150, 154, 153)	10.7	14.9	2.6
Swelling- severe (n= 149, 152, 152)	0	0	0
Tenderness- Any (n= 153, 155, 153)	7.8	7.1	2.6
Tenderness- Significant (n= 149, 152, 152)	0	0	0.7
Any local reaction (n=171, 163, 160)	62	55.8	28.8

Notes
[83] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[84] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[85] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Toddler Dose (12 to 15 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions: Toddler Dose (12 to 15 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 7 days after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series	DTaP (Catch-up 7vPnC) Toddler Series
Number of subjects analysed	153 ^[86]	152 ^[87]	151 ^[88]
Units: Percentage of subjects
number (not applicable)
Redness- Any (n= 148, 152, 149)	62.2	57.2	34.9
Redness- Mild (n= 148, 151, 148)	50	47.7	28.4
Redness- Moderate (n= 141, 139, 145)	27.7	27.3	13.1
Redness- Severe (n= 140, 136, 141)	0	0	0
Swelling- Any (n= 149, 144, 148)	49	45.8	26.4
Swelling- Mild (n= 147, 143, 146)	42.9	42	22.6
Swelling- Moderate (n= 143, 138, 146)	16.8	18.8	13
Swelling- severe (n= 140, 136, 141)	0	0	0
Tenderness- Any (n= 142, 140 ,142)	14.1	10	5.6
Tenderness- Significant (n= 140, 136, 141)	0.7	0	0
Any local reaction (n=153, 152, 151)	68.6	61.8	37.1

Notes
[86] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[87] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.
[88] - Subjects reporting yes for at least 1 day or no for all days for any local reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 1 (3 to 6 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 1 (3 to 6 Months of Age)

End point description

Systemic events (any fever >= 37.5 degrees Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population included all subjects who received at least 1 dose of study vaccine. 'n'=subjects reporting yes for at least 1 day or no for all days for specified systemic reaction for each group, respectively.

End point type

Other pre-specified

End point timeframe

Within 7 days after Dose 1 of infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	177 ^[89]	174 ^[90]	172 ^[91]
Units: Percentage of subjects
number (not applicable)
Fever >=37.5,=<39 degrees C (n=168, 168, 165)	36.3	33.9	21.8
Fever >39,=<40 degrees C (n=161, 163, 162)	0.6	1.2	0.6
Fever >40 degrees C (n=161, 162, 162)	0	0	0
Decreased appetite (n=163, 163, 165)	12.9	9.2	7.3
Irritability (n=165, 164, 164)	18.8	16.5	12.2
Increased sleep (n=170, 165, 165)	28.8	26.7	21.8
Decreased sleep (n=164, 169, 167)	18.3	21.3	13.8
Hives- urticaria (n=161, 162, 162)	3.1	1.2	0
Use of antipyretic medication (n= 161, 162, 162)	3.7	2.5	0.6
Any systemic event (n=177, 174, 172)	61	59.8	43

Notes
[89] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[90] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[91] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 2 (4 to 8 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 2 (4 to 8 Months of Age)

End point description

Systemic events (any fever >= 37.5 degrees C, decreased appetite, irritability, increased sleep, decreased sleep, and hives [urticaria]) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population included all subjects who received at least 1 dose of study vaccine. 'n'=subjects reporting yes for at least 1 day or no for all days for specified systemic reaction for each group, respectively.

End point type

Other pre-specified

End point timeframe

Within 7 days after Dose 2 of infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	170 ^[92]	169 ^[93]	166 ^[94]
Units: Percentage of subjects
number (not applicable)
Fever >=37.5, =<39 degrees C (n=166, 161, 155)	36.7	36.6	21.9
Fever >39, =<40 degrees C (n=158, 155, 154)	1.9	3.9	0.6
Fever >40 degrees C (n=157, 154, 154)	0	0	0
Decreased appetite (n=158, 159, 155)	11.4	14.5	7.1
Irritability (n=162, 155, 156)	17.9	18.7	10.9
Increased sleep (n=163, 158, 163)	22.7	22.2	22.7
Decreased sleep (n=161, 157, 157)	18.6	12.1	12.1
Hives- urticaria (n=157, 154, 154)	2.5	1.3	1.9
Use of antipyretic medication (n=160, 155, 154)	3.1	4.5	1.3
Any systemic event (n=170, 169, 166)	61.2	57.4	44.6

Notes
[92] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[93] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[94] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 3 (5 to 10 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 3 (5 to 10 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 7 days after Dose 3 of infant series

End point values	13vPnC + DTaP Infant Series	7vPnC + DTaP Infant Series	DTaP (Catch-up 7vPnC) Infant Series
Number of subjects analysed	168 ^[95]	164 ^[96]	159 ^[97]
Units: Percentage of subjects
number (not applicable)
Fever >=37.5, =<39 degrees C (n=162, 161, 157)	34.6	30.4	24.2
Fever >39, =<40 degrees C (n=150, 152, 153)	3.3	2	3.3
Fever >40 degrees C (n=149, 152, 152)	0	0.7	0
Decreased appetite (n=152, 155, 154)	9.9	9.7	5.8
Irritability (n=154, 156, 154)	17.5	14.7	11.7
Increased sleep (n=151, 157, 154)	20.5	20.4	14.9
Decreased sleep (n= 154, 156, 153)	18.2	12.8	9.8
Hives- urticaria (n= 149, 152, 152)	1.3	0	1.3
Use of antipyretic medication (n=150, 153, 154)	2	3.3	4.5
Any systemic event (n=168, 164, 159)	57.7	50	40.9

Notes
[95] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[96] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[97] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Toddler Dose (12 to 15 Months of Age)

Top of page

End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events: Toddler Dose (12 to 15 Months of Age)

End point description

End point type

Other pre-specified

End point timeframe

Within 7 days after the toddler dose

End point values	13vPnC + DTaP Toddler Series	7vPnC + DTaP Toddler Series	DTaP (Catch-up 7vPnC) Toddler Series
Number of subjects analysed	148 ^[98]	152 ^[99]	149 ^[100]
Units: Percentage of subjects
number (not applicable)
Fever >=37.5, =<39 degrees C (n=145, 146, 146)	49	49.3	31.5
Fever >39, =<40 degrees C (n=141, 136, 141)	4.3	8.8	3.5
Fever >40 degrees C (n=139, 137, 141)	1.4	2.2	0
Decreased appetite (n=143, 141, 143)	19.6	19.9	9.8
Irritability (n=143, 141, 144)	18.2	21.3	16.7
Increased sleep (n=145, 142, 143)	18.6	17.6	16.1
Decreased sleep (n=142, 137, 141)	12.7	9.5	11.3
Hives- urticaria (n=140, 136, 141)	3.6	2.2	2.1
Use of antipyretic medication (n=141, 138, 142)	7.1	9.4	4.2
Any systemic event (n=148, 152, 149)	62.8	63.8	50.3

Notes
[98] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[99] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.
[100] - Subjects reporting yes for at least 1 day or no for all days for any systemic reaction.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

SAEs: from signing of ICF through study completion. AEs: from signing of ICF to 28 days after infant series dose 3 (Groups 1, 2), 28 days after catch-up dose 2 (Group 3), 28 days after toddler dose (Groups 1, 2) and 28 days after catch-up dose 3 (Group 3)

Adverse event reporting additional description

SAEs and AEs were grouped by system organ class and summarized. AEs included solicited AEs collected in electronic diary (local and systemic reactions;systematic assessment) and unsolicited events collected on case report form at each visit(nonsystematic assessment). LRs and SEs were to be assessed only for infant series and toddler dose groups.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

13vPnC + DTaP - Infant Series

Reporting group description

Subjects who received 3 single 0.5 mL doses of 13vPnC subcutaneously 4 to 8 weeks apart along with 3 single 0.5 mL doses of DTaP subcutaneously (infant series), assessed from Infant Dose 1 through the blood draw 28 to 42 days post-infant series.

Reporting group title

7vPnC + DTaP - Infant Series

Reporting group description

Subjects who received 3 single 0.5 mL doses of 7vPnC subcutaneously 4 to 8 weeks apart along with 3 single 0.5 mL doses of DTaP subcutaneously (infant series), assessed from Infant Dose 1 through the blood draw 28 to 42 days post-infant series.

Reporting group title

DTaP (Catch-up 7vPnC) - Infant Series

Reporting group description

Subjects who received 3 single 0.5 mL DTaP doses subcutaneously 4 to 8 weeks apart (infant series) followed by 2 single CU doses, CU Dose 1 and CU Dose 2 (separated by 4 to 6 weeks), of 7vPnC (Prevenar) 4 to 6 weeks post-infant series, assessed from Infant Dose 1 through the CU Dose 1.

Reporting group title

13vPnC + DTaP - After the Infant Series

Reporting group description

Subjects who received 3 single 0.5 mL doses of 13vPnC subcutaneously 4 to 8 weeks apart along with 3 single 0.5 mL doses of DTaP subcutaneously (infant series), assessed after the infant series blood draw to the toddler dose.

Reporting group title

7vPnC + DTaP - After the Infant Series

Reporting group description

Reporting group title

DTaP (Catch-up 7vPnC) - After the Infant Series

Reporting group description

Reporting group title

13vPnC + DTaP - Toddler Dose

Reporting group description

Subjects who received a single 0.5 mL dose of 13vPnC subcutaneously (toddler dose) along with 0.5 mL dose of DTaP subcutaneously, assessed from the toddler dose through the blood draw 28 to 42 days post-toddler dose.

Reporting group title

7vPnC + DTaP - Toddler Dose

Reporting group description

Subjects who received a single 0.5 mL dose of 7vPnC subcutaneously (toddler dose) along with 0.5 mL dose of DTaP subcutaneously, assessed from the toddler dose through the blood draw 28 to 42 days post-toddler dose.

Reporting group title

DTaP (Catch-up 7vPnC) - Toddler Dose

Reporting group description

Subjects who received a single 0.5 mL DTaP dose subcutaneously (toddler dose) followed by a single CU dose (CU Dose 3) of 7vPnC (Prevenar) 4 to 6 weeks after toddler dose; assessed from toddler dose through the CU Dose 3.

Reporting group title

DTaP (Catch-up 7vPnC) - After the Toddler Dose

Reporting group description

Subjects who received a single 0.5 mL DTaP dose subcutaneously (toddler dose) followed by a single CU dose (CU Dose 3) of 7vPnC (Prevenar) 4 to 6 weeks after toddler dose; assessed after the CU Dose 3 to 28 to 42 days post-CU Dose 3.

Serious adverse events	13vPnC + DTaP - Infant Series	7vPnC + DTaP - Infant Series	DTaP (Catch-up 7vPnC) - Infant Series	13vPnC + DTaP - After the Infant Series	7vPnC + DTaP - After the Infant Series	DTaP (Catch-up 7vPnC) - After the Infant Series	13vPnC + DTaP - Toddler Dose	7vPnC + DTaP - Toddler Dose	DTaP (Catch-up 7vPnC) - Toddler Dose	DTaP (Catch-up 7vPnC) - After the Toddler Dose
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 183 (2.73%)	8 / 183 (4.37%)	10 / 183 (5.46%)	13 / 183 (7.10%)	15 / 183 (8.20%)	10 / 183 (5.46%)	0 / 162 (0.00%)	4 / 162 (2.47%)	2 / 169 (1.18%)	2 / 169 (1.18%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Thermal burn
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Congenital, familial and genetic disorders
Dacryostenosis congenital
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	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	0 / 0	0 / 0
Vascular disorders
Kawasaki's disease
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	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	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 183 (0.55%)	6 / 183 (3.28%)	5 / 183 (2.73%)	3 / 183 (1.64%)	0 / 162 (0.00%)	3 / 162 (1.85%)	1 / 169 (0.59%)	2 / 169 (1.18%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 7	0 / 6	0 / 3	0 / 0	0 / 3	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuritis cranial
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	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	0 / 0	0 / 0
Ear and labyrinth disorders
Deafness bilateral
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	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	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscular weakness
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	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	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 2	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	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Exanthema subitum
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	3 / 183 (1.64%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 3	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	0 / 0	0 / 0
Gastroenteritis norovirus
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	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	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	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	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	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	0 / 0	0 / 0
Herpangina
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Laryngitis
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	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	0 / 0	0 / 0
Mycoplasma infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Otitis media
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Parotitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	3 / 183 (1.64%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	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	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	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	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	3 / 183 (1.64%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	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	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Rotavirus infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	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	0 / 0	0 / 0

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

Non-serious adverse events	13vPnC + DTaP - Infant Series	7vPnC + DTaP - Infant Series	DTaP (Catch-up 7vPnC) - Infant Series	13vPnC + DTaP - After the Infant Series	7vPnC + DTaP - After the Infant Series	DTaP (Catch-up 7vPnC) - After the Infant Series	13vPnC + DTaP - Toddler Dose	7vPnC + DTaP - Toddler Dose	DTaP (Catch-up 7vPnC) - Toddler Dose	DTaP (Catch-up 7vPnC) - After the Toddler Dose
Total subjects affected by non serious adverse events
subjects affected / exposed	177 / 183 (96.72%)	174 / 183 (95.08%)	172 / 183 (93.99%)	20 / 183 (10.93%)	27 / 183 (14.75%)	147 / 183 (80.33%)	153 / 162 (94.44%)	152 / 162 (93.83%)	151 / 169 (89.35%)	105 / 169 (62.13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma of skin
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Vascular disorders
Haematoma
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Kawasaki's disease
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	1	0	1	0	1	0	0	0
General disorders and administration site conditions
Application site erythema
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0
Injection site dermatitis
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	5	0	0	0	0	0	0	0	0
Injection site erythema
subjects affected / exposed	1 / 183 (0.55%)	4 / 183 (2.19%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	2 / 162 (1.23%)	1 / 162 (0.62%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	2	7	0	0	0	2	2	1	1	0
Injection site induration
subjects affected / exposed	1 / 183 (0.55%)	3 / 183 (1.64%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	1	3	0	0	0	1	0	0	1	0
Injection site swelling
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	1 / 162 (0.62%)	1 / 162 (0.62%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	1	0	0	0	0	2	1	1	0	1
Pyrexia
subjects affected / exposed	4 / 183 (2.19%)	5 / 183 (2.73%)	6 / 183 (3.28%)	0 / 183 (0.00%)	0 / 183 (0.00%)	12 / 183 (6.56%)	3 / 162 (1.85%)	5 / 162 (3.09%)	2 / 169 (1.18%)	1 / 169 (0.59%)
occurrences all number	4	5	6	0	0	13	3	5	2	1
Vaccination site induration
subjects affected / exposed	0 / 183 (0.00%)	3 / 183 (1.64%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0	0
Vaccination site erythema
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Vaccination site swelling
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Fever ≥37.5°C but ≤39°C Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	61 / 168 (36.31%)	57 / 168 (33.93%)	36 / 165 (21.82%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	71 / 145 (48.97%)	72 / 146 (49.32%)	46 / 146 (31.51%)	0 / 169 (0.00%)
occurrences all number	61	57	36	0	0	0	71	72	46	0
Fever >39°C but ≤40°C Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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 / 161 (0.62%)	2 / 163 (1.23%)	1 / 162 (0.62%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	6 / 141 (4.26%)	12 / 136 (8.82%)	5 / 141 (3.55%)	0 / 169 (0.00%)
occurrences all number	1	2	1	0	0	0	6	12	5	0
Fever >40°C Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	0 / 161 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 139 (1.44%)	3 / 137 (2.19%)	0 / 141 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	2	3	0	0
Decreased appetite Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	21 / 163 (12.88%)	15 / 163 (9.20%)	12 / 165 (7.27%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	28 / 143 (19.58%)	28 / 141 (19.86%)	14 / 143 (9.79%)	0 / 169 (0.00%)
occurrences all number	21	15	12	0	0	0	28	28	14	0
Irritability Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	31 / 165 (18.79%)	27 / 164 (16.46%)	20 / 164 (12.20%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	26 / 143 (18.18%)	30 / 141 (21.28%)	24 / 144 (16.67%)	0 / 169 (0.00%)
occurrences all number	31	27	20	0	0	0	26	30	24	0
Increased sleep Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	49 / 170 (28.82%)	44 / 165 (26.67%)	36 / 165 (21.82%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	27 / 145 (18.62%)	25 / 142 (17.61%)	23 / 143 (16.08%)	0 / 169 (0.00%)
occurrences all number	49	44	36	0	0	0	27	25	23	0
Decreased sleep Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	30 / 164 (18.29%)	36 / 169 (21.30%)	23 / 167 (13.77%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	18 / 142 (12.68%)	13 / 137 (9.49%)	16 / 141 (11.35%)	0 / 169 (0.00%)
occurrences all number	30	36	23	0	0	0	18	13	16	0
Hives (urticaria) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	5 / 161 (3.11%)	2 / 162 (1.23%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	5 / 140 (3.57%)	3 / 136 (2.21%)	3 / 141 (2.13%)	0 / 169 (0.00%)
occurrences all number	5	2	0	0	0	0	5	3	3	0
Use of antipyretic medication to treat symptoms Dose 1
Additional description: Dose 1: Subjects affected and occurrences for SE 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]	6 / 161 (3.73%)	4 / 162 (2.47%)	1 / 162 (0.62%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	10 / 141 (7.09%)	13 / 138 (9.42%)	6 / 142 (4.23%)	0 / 169 (0.00%)
occurrences all number	6	4	1	0	0	0	10	13	6	0
Fever ≥37.5°C but ≤39°C Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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]	61 / 166 (36.75%)	59 / 161 (36.65%)	34 / 155 (21.94%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	61	59	34	0	0	0	0	0	0	0
Fever >39°C but ≤40°C Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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]	3 / 158 (1.90%)	6 / 155 (3.87%)	1 / 154 (0.65%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	3	6	1	0	0	0	0	0	0	0
Decreased appetite Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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]	18 / 158 (11.39%)	23 / 159 (14.47%)	11 / 155 (7.10%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	18	23	11	0	0	0	0	0	0	0
Irritability Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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 ^[13]	29 / 162 (17.90%)	29 / 155 (18.71%)	17 / 156 (10.90%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	29	29	17	0	0	0	0	0	0	0
Increased sleep Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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 ^[14]	37 / 163 (22.70%)	35 / 158 (22.15%)	37 / 163 (22.70%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	37	35	37	0	0	0	0	0	0	0
Decreased sleep Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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 ^[15]	30 / 161 (18.63%)	19 / 157 (12.10%)	19 / 157 (12.10%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	30	19	19	0	0	0	0	0	0	0
Hives (urticaria) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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 ^[16]	4 / 157 (2.55%)	2 / 154 (1.30%)	3 / 154 (1.95%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	4	2	3	0	0	0	0	0	0	0
Use of antipyretic medication to treat symptoms Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE 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 ^[17]	5 / 160 (3.13%)	7 / 155 (4.52%)	2 / 154 (1.30%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	5	7	2	0	0	0	0	0	0	0
Fever ≥37.5°C but ≤39°C Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[18]	56 / 162 (34.57%)	49 / 161 (30.43%)	38 / 157 (24.20%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	56	49	38	0	0	0	0	0	0	0
Fever >39°C but ≤40°C Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[19]	5 / 150 (3.33%)	3 / 152 (1.97%)	5 / 153 (3.27%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	5	3	5	0	0	0	0	0	0	0
Fever >40°C Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[20]	0 / 149 (0.00%)	1 / 152 (0.66%)	0 / 152 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Decreased appetite Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[21]	15 / 152 (9.87%)	15 / 155 (9.68%)	9 / 154 (5.84%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	15	15	9	0	0	0	0	0	0	0
Irritability Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[22]	27 / 154 (17.53%)	23 / 156 (14.74%)	18 / 154 (11.69%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	27	23	18	0	0	0	0	0	0	0
Increased sleep Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[23]	31 / 151 (20.53%)	32 / 157 (20.38%)	23 / 154 (14.94%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	31	32	23	0	0	0	0	0	0	0
Decreased sleep Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[24]	28 / 154 (18.18%)	20 / 156 (12.82%)	15 / 153 (9.80%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	28	20	15	0	0	0	0	0	0	0
Use of antipyretic medication to treat symptoms Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[25]	3 / 150 (2.00%)	5 / 153 (3.27%)	7 / 154 (4.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	3	5	7	0	0	0	0	0	0	0
Immune system disorders
Food allergy
subjects affected / exposed	2 / 183 (1.09%)	2 / 183 (1.09%)	2 / 183 (1.09%)	6 / 183 (3.28%)	3 / 183 (1.64%)	6 / 183 (3.28%)	2 / 162 (1.23%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	2	2	2	6	3	6	2	0	1	0
Milk allergy
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
Breast swelling
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Genital labial adhesions
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Posthitis
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Asthma
subjects affected / exposed	6 / 183 (3.28%)	3 / 183 (1.64%)	10 / 183 (5.46%)	5 / 183 (2.73%)	6 / 183 (3.28%)	15 / 183 (8.20%)	1 / 162 (0.62%)	2 / 162 (1.23%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	7	5	11	5	6	16	1	2	0	0
Epistaxis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0
Fibrinous bronchitis
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	1	0	0	0	1	0	0	0	0
Infantile asthma
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0
Nasal obstruction
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Pulmonary artery stenosis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	3 / 183 (1.64%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	2	1	0	1	3	0	0	0	0
Rhinorrhoea
subjects affected / exposed	5 / 183 (2.73%)	2 / 183 (1.09%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	2 / 162 (1.23%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	9	3	3	0	0	2	2	0	0	0
Investigations
Body height below normal
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Injury, poisoning and procedural complications
Arthropod sting
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	2 / 162 (1.23%)	2 / 162 (1.23%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	1	2	2	1	0
Arthropod bite
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	2 / 162 (1.23%)	5 / 169 (2.96%)	5 / 169 (2.96%)
occurrences all number	0	0	0	0	0	0	1	2	5	5
Chillblains
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	1	0	0	0	0	1	0	0	0	1
Ear injury
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0
Excoriation
subjects affected / exposed	1 / 183 (0.55%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0
Fall
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	3 / 183 (1.64%)	1 / 162 (0.62%)	1 / 162 (0.62%)	2 / 169 (1.18%)	1 / 169 (0.59%)
occurrences all number	0	2	1	0	0	3	1	1	2	1
Head injury
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Joint dislocation
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Scratch
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Thermal burn
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	1	0	0	1	1
Frostbite
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0
Congenital, familial and genetic disorders
Dacryostenosis congenita
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Nervous system disorders
Neuritis cranial
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Iron deficiency anaemia
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	3 / 183 (1.64%)	3 / 183 (1.64%)	4 / 183 (2.19%)	0 / 162 (0.00%)	2 / 162 (1.23%)	2 / 169 (1.18%)	1 / 169 (0.59%)
occurrences all number	0	0	0	3	3	4	0	2	2	1
Lymphadenopathy
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Ear and labyrinth disorders
Ear haemorrhage
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Eye disorders
Blepharitis
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	7 / 183 (3.83%)	11 / 183 (6.01%)	20 / 183 (10.93%)	0 / 183 (0.00%)	0 / 183 (0.00%)	9 / 183 (4.92%)	2 / 162 (1.23%)	3 / 162 (1.85%)	2 / 169 (1.18%)	6 / 169 (3.55%)
occurrences all number	9	13	23	0	0	11	2	3	2	6
Conjunctivitis allergic
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Dacryostenosis acquired
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Eye discharge
subjects affected / exposed	7 / 183 (3.83%)	5 / 183 (2.73%)	3 / 183 (1.64%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	9	5	4	0	0	1	0	0	0	0
Eye pruritus
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Eyelid oedema
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Keratitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0
Gastrointestinal disorders
Acetonaemic vomiting
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Anal fissure
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Cheilitis
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	2 / 183 (1.09%)	4 / 183 (2.19%)	3 / 183 (1.64%)	3 / 183 (1.64%)	0 / 183 (0.00%)	5 / 183 (2.73%)	0 / 162 (0.00%)	0 / 162 (0.00%)	2 / 169 (1.18%)	1 / 169 (0.59%)
occurrences all number	2	5	3	3	0	6	0	0	2	1
Diarrhoea
subjects affected / exposed	10 / 183 (5.46%)	9 / 183 (4.92%)	5 / 183 (2.73%)	0 / 183 (0.00%)	1 / 183 (0.55%)	5 / 183 (2.73%)	3 / 162 (1.85%)	3 / 162 (1.85%)	5 / 169 (2.96%)	1 / 169 (0.59%)
occurrences all number	10	10	5	0	1	5	3	3	5	1
Dyspepsia
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Haematochezia
subjects affected / exposed	1 / 183 (0.55%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Melaena
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Vomiting
subjects affected / exposed	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	1	0	0	0	1	0	0	0	0
Hives (urticaria) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE 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 ^[26]	2 / 149 (1.34%)	0 / 152 (0.00%)	2 / 152 (1.32%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	0	2	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Onychomadesis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Asteatosis
subjects affected / exposed	8 / 183 (4.37%)	7 / 183 (3.83%)	5 / 183 (2.73%)	1 / 183 (0.55%)	3 / 183 (1.64%)	2 / 183 (1.09%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	8	7	5	1	3	2	0	0	0	0
Dermatitis
subjects affected / exposed	2 / 183 (1.09%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	0	1	0	0	3	0	0	0	0
Dermatitis atopic
subjects affected / exposed	4 / 183 (2.19%)	0 / 183 (0.00%)	3 / 183 (1.64%)	2 / 183 (1.09%)	1 / 183 (0.55%)	1 / 183 (0.55%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	4	0	3	2	1	1	1	0	0	0
Dermatitis contact
subjects affected / exposed	4 / 183 (2.19%)	5 / 183 (2.73%)	5 / 183 (2.73%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 162 (0.00%)	1 / 162 (0.62%)	1 / 169 (0.59%)	1 / 169 (0.59%)
occurrences all number	5	5	5	0	0	2	0	1	1	1
Dermatitis diaper
subjects affected / exposed	16 / 183 (8.74%)	19 / 183 (10.38%)	26 / 183 (14.21%)	1 / 183 (0.55%)	0 / 183 (0.00%)	19 / 183 (10.38%)	5 / 162 (3.09%)	6 / 162 (3.70%)	1 / 169 (0.59%)	5 / 169 (2.96%)
occurrences all number	17	20	29	1	0	23	5	6	1	5
Dry skin
subjects affected / exposed	7 / 183 (3.83%)	2 / 183 (1.09%)	5 / 183 (2.73%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	8	2	5	0	1	1	0	0	0	0
Eczema
subjects affected / exposed	24 / 183 (13.11%)	26 / 183 (14.21%)	27 / 183 (14.75%)	1 / 183 (0.55%)	2 / 183 (1.09%)	17 / 183 (9.29%)	3 / 162 (1.85%)	5 / 162 (3.09%)	5 / 169 (2.96%)	5 / 169 (2.96%)
occurrences all number	25	34	30	1	2	19	3	5	5	5
Eczema asteatotic
subjects affected / exposed	9 / 183 (4.92%)	8 / 183 (4.37%)	4 / 183 (2.19%)	0 / 183 (0.00%)	1 / 183 (0.55%)	2 / 183 (1.09%)	2 / 162 (1.23%)	0 / 162 (0.00%)	3 / 169 (1.78%)	0 / 169 (0.00%)
occurrences all number	11	8	4	0	1	2	2	0	3	0
Eczema infantile
subjects affected / exposed	12 / 183 (6.56%)	7 / 183 (3.83%)	7 / 183 (3.83%)	0 / 183 (0.00%)	0 / 183 (0.00%)	4 / 183 (2.19%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	13	8	7	0	0	5	0	0	0	0
Erythema
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	2	0	0	0	1	0	0	0	0
Haemorrhage subcutaneous
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Heat rash
subjects affected / exposed	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	4 / 183 (2.19%)	5 / 162 (3.09%)	6 / 162 (3.70%)	5 / 169 (2.96%)	4 / 169 (2.37%)
occurrences all number	2	1	0	0	0	4	5	6	5	4
Hyperkeratosis palmaris and plantaris
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Papule
subjects affected / exposed	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
Pityriasis rosea
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Rash generalised
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Scar
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Seborrhoeic dermatitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Rash
subjects affected / exposed	6 / 183 (3.28%)	2 / 183 (1.09%)	5 / 183 (2.73%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	2 / 162 (1.23%)	3 / 162 (1.85%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	7	2	6	0	0	3	2	3	0	0
Urticaria
subjects affected / exposed	3 / 183 (1.64%)	5 / 183 (2.73%)	4 / 183 (2.19%)	0 / 183 (0.00%)	0 / 183 (0.00%)	4 / 183 (2.19%)	2 / 162 (1.23%)	2 / 162 (1.23%)	1 / 169 (0.59%)	2 / 169 (1.18%)
occurrences all number	3	5	4	0	0	4	3	2	1	2
Redness(Any) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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]	100 / 171 (58.48%)	96 / 172 (55.81%)	17 / 165 (10.30%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	92 / 148 (62.16%)	87 / 152 (57.24%)	52 / 149 (34.90%)	0 / 169 (0.00%)
occurrences all number	100	96	17	0	0	0	92	87	52	0
Redness (Mild) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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]	82 / 170 (48.24%)	88 / 172 (51.16%)	17 / 165 (10.30%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	74 / 148 (50.00%)	72 / 151 (47.68%)	42 / 148 (28.38%)	0 / 169 (0.00%)
occurrences all number	82	88	17	0	0	0	74	72	42	0
Redness (Moderate) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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]	31 / 164 (18.90%)	30 / 166 (18.07%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	39 / 141 (27.66%)	38 / 139 (27.34%)	19 / 145 (13.10%)	0 / 169 (0.00%)
occurrences all number	31	30	0	0	0	0	39	38	19	0
Redness (Severe) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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]	0 / 161 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 140 (0.00%)	0 / 136 (0.00%)	0 / 141 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Swelling (Any) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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 ^[31]	69 / 168 (41.07%)	60 / 168 (35.71%)	8 / 164 (4.88%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	73 / 149 (48.99%)	66 / 144 (45.83%)	39 / 148 (26.35%)	0 / 169 (0.00%)
occurrences all number	69	168	164	0	0	0	73	66	39	0
Swelling (Mild) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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 ^[32]	64 / 168 (38.10%)	53 / 168 (31.55%)	8 / 164 (4.88%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	63 / 147 (42.86%)	60 / 143 (41.96%)	33 / 146 (22.60%)	0 / 169 (0.00%)
occurrences all number	64	53	8	0	0	0	147	143	146	0
Swelling (Moderate) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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 ^[33]	20 / 162 (12.35%)	21 / 165 (12.73%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	24 / 143 (16.78%)	26 / 138 (18.84%)	19 / 146 (13.01%)	0 / 169 (0.00%)
occurrences all number	20	21	0	0	0	0	24	26	19	0
Swelling (Severe) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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 ^[34]	0 / 161 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 140 (0.00%)	0 / 136 (0.00%)	0 / 141 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Tenderness (Any) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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 ^[35]	22 / 163 (13.50%)	10 / 164 (6.10%)	2 / 162 (1.23%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	20 / 142 (14.08%)	14 / 140 (10.00%)	8 / 142 (5.63%)	0 / 169 (0.00%)
occurrences all number	22	10	2	0	0	0	20	14	8	0
Tenderness (Significant) Dose 1
Additional description: Dose 1: Subjects affected and occurrences for LR 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 ^[36]	0 / 161 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 140 (0.71%)	0 / 136 (0.00%)	0 / 141 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Redness (Any) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[37]	104 / 166 (62.65%)	104 / 168 (61.90%)	59 / 161 (36.65%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	104	104	59	0	0	0	0	0	0	0
Redness (Mild) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[38]	93 / 166 (56.02%)	95 / 167 (56.89%)	56 / 161 (34.78%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	93	95	56	0	0	0	0	0	0	0
Redness (Moderate) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[39]	41 / 157 (26.11%)	43 / 159 (27.04%)	13 / 156 (8.33%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	41	43	13	0	0	0	0	0	0	0
Swelling (Any) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[40]	77 / 160 (48.13%)	87 / 171 (50.88%)	39 / 162 (24.07%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	77	87	39	0	0	0	0	0	0	0
Swelling (Mild) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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
subjects affected / exposed ^[41]	71 / 160 (44.38%)	82 / 170 (48.24%)	37 / 162 (22.84%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	71	82	37	0	0	0	0	0	0	0
Swelling (Moderate) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[42]	31 / 157 (19.75%)	28 / 157 (17.83%)	9 / 155 (5.81%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	31	28	9	0	0	0	0	0	0	0
Tenderness (Any) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[43]	23 / 159 (14.47%)	7 / 154 (4.55%)	3 / 155 (1.94%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	23	7	3	0	0	0	0	0	0	0
Tenderness (Significant) Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[44]	1 / 157 (0.64%)	0 / 154 (0.00%)	0 / 154 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Redness (Any) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[45]	90 / 168 (53.57%)	83 / 162 (51.23%)	36 / 156 (23.08%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	90	83	36	0	0	0	0	0	0	0
Redness (Mild) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[46]	79 / 167 (47.31%)	69 / 160 (43.13%)	34 / 156 (21.79%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	79	69	34	0	0	0	0	0	0	0
Redness (Moderate) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[47]	26 / 152 (17.11%)	34 / 154 (22.08%)	3 / 153 (1.96%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	26	34	3	0	0	0	0	0	0	0
Swelling (Any) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[48]	72 / 164 (43.90%)	59 / 157 (37.58%)	34 / 159 (21.38%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	72	59	34	0	0	0	0	0	0	0
Swelling (Mild) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[49]	69 / 164 (42.07%)	53 / 156 (33.97%)	32 / 159 (20.13%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	69	53	32	0	0	0	0	0	0	0
Swelling (Moderate) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[50]	16 / 150 (10.67%)	23 / 154 (14.94%)	4 / 153 (2.61%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	16	23	4	0	0	0	0	0	0	0
Tenderness (Any) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[51]	12 / 153 (7.84%)	11 / 155 (7.10%)	4 / 153 (2.61%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	12	11	4	0	0	0	0	0	0	0
Tenderness (Significant) Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[52]	0 / 149 (0.00%)	0 / 152 (0.00%)	1 / 152 (0.66%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Renal and urinary disorders
Vesicoureteric reflux
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Infections and infestations
Acute sinusitis
subjects affected / exposed	2 / 183 (1.09%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	1	2	0	0	0	0	0	0	0
Adenoviral conjunctivitis
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	3 / 169 (1.78%)	0 / 169 (0.00%)
occurrences all number	1	1	0	0	0	0	0	1	3	0
Adenovirus infection
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	1	0	0	1	1	0	0	0
Anal abscess
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Anal fungal infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Bacterial infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Bronchiolitis
subjects affected / exposed	2 / 183 (1.09%)	2 / 183 (1.09%)	5 / 183 (2.73%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 162 (0.00%)	1 / 162 (0.62%)	1 / 169 (0.59%)	1 / 169 (0.59%)
occurrences all number	2	2	5	0	0	2	0	1	1	1
Bronchitis
subjects affected / exposed	24 / 183 (13.11%)	28 / 183 (15.30%)	26 / 183 (14.21%)	0 / 183 (0.00%)	0 / 183 (0.00%)	35 / 183 (19.13%)	8 / 162 (4.94%)	9 / 162 (5.56%)	13 / 169 (7.69%)	16 / 169 (9.47%)
occurrences all number	40	43	36	0	0	44	9	9	13	18
Candidiasis
subjects affected / exposed	1 / 183 (0.55%)	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 162 (0.62%)	1 / 162 (0.62%)	0 / 169 (0.00%)	2 / 169 (1.18%)
occurrences all number	1	2	1	0	0	1	1	1	0	2
Conjunctivitis bacterial
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	1	1	1	0	0	1	0	0	0	1
Conjunctivitis infective
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Conjunctivitis viral
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Croup infectious
subjects affected / exposed	3 / 183 (1.64%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 162 (0.62%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	3	1	0	0	0	1	1	0	1	0
Enteritis infectious
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	4 / 183 (2.19%)	0 / 183 (0.00%)	0 / 183 (0.00%)	5 / 183 (2.73%)	1 / 162 (0.62%)	0 / 162 (0.00%)	1 / 169 (0.59%)	2 / 169 (1.18%)
occurrences all number	1	1	5	0	0	6	1	0	1	2
Echo virus infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Erythema infectiosum
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	2	0	1	0	0
Exanthema subitum
subjects affected / exposed	10 / 183 (5.46%)	17 / 183 (9.29%)	19 / 183 (10.38%)	0 / 183 (0.00%)	0 / 183 (0.00%)	22 / 183 (12.02%)	6 / 162 (3.70%)	3 / 162 (1.85%)	3 / 169 (1.78%)	4 / 169 (2.37%)
occurrences all number	10	17	19	0	0	22	6	3	3	4
Folliculitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	1	0	0	0	1
Gastroenteritis
subjects affected / exposed	28 / 183 (15.30%)	24 / 183 (13.11%)	31 / 183 (16.94%)	0 / 183 (0.00%)	0 / 183 (0.00%)	30 / 183 (16.39%)	3 / 162 (1.85%)	7 / 162 (4.32%)	5 / 169 (2.96%)	9 / 169 (5.33%)
occurrences all number	30	26	38	0	0	37	3	7	5	9
Gastroenteritis norovirus
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	1	2	0	0	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	7 / 183 (3.83%)	9 / 183 (4.92%)	7 / 183 (3.83%)	0 / 183 (0.00%)	0 / 183 (0.00%)	8 / 183 (4.37%)	0 / 162 (0.00%)	2 / 162 (1.23%)	1 / 169 (0.59%)	2 / 169 (1.18%)
occurrences all number	7	10	8	0	0	9	0	2	1	2
Genital infection fungal
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	2	1	0	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	1	0
Impetigo
subjects affected / exposed	3 / 183 (1.64%)	3 / 183 (1.64%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	4 / 183 (2.19%)	1 / 162 (0.62%)	4 / 162 (2.47%)	4 / 169 (2.37%)	2 / 169 (1.18%)
occurrences all number	3	3	2	0	0	4	1	4	4	2
Influenza
subjects affected / exposed	3 / 183 (1.64%)	4 / 183 (2.19%)	6 / 183 (3.28%)	0 / 183 (0.00%)	0 / 183 (0.00%)	13 / 183 (7.10%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	3	4	6	0	0	13	0	0	0	0
Laryngitis
subjects affected / exposed	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	2	0	0	0	0	1	0	0	0
Molluscum contagiosum
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	3 / 183 (1.64%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	1 / 169 (0.59%)
occurrences all number	1	1	0	0	0	3	0	0	1	1
Nasopharyngitis
subjects affected / exposed	48 / 183 (26.23%)	58 / 183 (31.69%)	51 / 183 (27.87%)	1 / 183 (0.55%)	2 / 183 (1.09%)	42 / 183 (22.95%)	32 / 162 (19.75%)	21 / 162 (12.96%)	28 / 169 (16.57%)	27 / 169 (15.98%)
occurrences all number	72	90	74	1	2	68	36	23	32	30
Oral candidiasis
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	0	0	0	0	1	0	0	0	0
Oral fungal infection
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Otitis externa
subjects affected / exposed	1 / 183 (0.55%)	2 / 183 (1.09%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	1	2	1	0	0	1	0	0	1	0
Otitis media
subjects affected / exposed	8 / 183 (4.37%)	6 / 183 (3.28%)	7 / 183 (3.83%)	1 / 183 (0.55%)	0 / 183 (0.00%)	8 / 183 (4.37%)	4 / 162 (2.47%)	4 / 162 (2.47%)	5 / 169 (2.96%)	7 / 169 (4.14%)
occurrences all number	11	6	7	1	0	10	4	5	5	7
Otitis media acute
subjects affected / exposed	0 / 183 (0.00%)	5 / 183 (2.73%)	3 / 183 (1.64%)	0 / 183 (0.00%)	0 / 183 (0.00%)	7 / 183 (3.83%)	4 / 162 (2.47%)	0 / 162 (0.00%)	1 / 169 (0.59%)	1 / 169 (0.59%)
occurrences all number	0	7	3	0	0	8	4	0	1	1
Perirectal abscess
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	3 / 183 (1.64%)	3 / 183 (1.64%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	6 / 183 (3.28%)	4 / 162 (2.47%)	3 / 162 (1.85%)	2 / 169 (1.18%)	1 / 169 (0.59%)
occurrences all number	3	3	2	0	0	6	4	3	2	1
Pharyngotonsillitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0
Pneumococcal bacteraemia
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	2	1	0	0	1	0	0	0	0
Pneumonia respiratory syncytial viral
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Rash pustular
subjects affected / exposed	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Respiratory syncytial virus bronchitis
subjects affected / exposed	2 / 183 (1.09%)	1 / 183 (0.55%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	1	2	0	0	0	0	0	0	0
Respiratory syncytial virus infection
subjects affected / exposed	9 / 183 (4.92%)	14 / 183 (7.65%)	4 / 183 (2.19%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	1 / 162 (0.62%)	1 / 169 (0.59%)	2 / 169 (1.18%)
occurrences all number	9	14	4	0	0	1	0	1	1	2
Respiratory tract infection
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	2 / 183 (1.09%)	3 / 183 (1.64%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	3	2	0	0	0	1	0	0	0
Sinusitis
subjects affected / exposed	2 / 183 (1.09%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	2	0	2	0	0	1	0	0	0	0
Skin candida
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	1 / 162 (0.62%)	0 / 162 (0.00%)	1 / 169 (0.59%)	0 / 169 (0.00%)
occurrences all number	1	1	0	0	0	1	1	0	1	0
Skin infection
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	1	1	0	0	0	0	0	1	0	1
Tonsillitis
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	3 / 183 (1.64%)	0 / 183 (0.00%)	0 / 183 (0.00%)	4 / 183 (2.19%)	0 / 162 (0.00%)	3 / 162 (1.85%)	2 / 169 (1.18%)	1 / 169 (0.59%)
occurrences all number	1	1	4	0	0	4	0	3	2	1
Upper respiratory tract infection
subjects affected / exposed	54 / 183 (29.51%)	67 / 183 (36.61%)	65 / 183 (35.52%)	0 / 183 (0.00%)	0 / 183 (0.00%)	62 / 183 (33.88%)	20 / 162 (12.35%)	19 / 162 (11.73%)	28 / 169 (16.57%)	25 / 169 (14.79%)
occurrences all number	78	102	109	0	0	82	26	20	31	28
Urinary tract infection
subjects affected / exposed	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0
Varicella
subjects affected / exposed	4 / 183 (2.19%)	8 / 183 (4.37%)	4 / 183 (2.19%)	0 / 183 (0.00%)	0 / 183 (0.00%)	3 / 183 (1.64%)	2 / 162 (1.23%)	0 / 162 (0.00%)	0 / 169 (0.00%)	2 / 169 (1.18%)
occurrences all number	4	8	4	0	0	3	2	0	0	2
Viral infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	1	0	0	0	1	1	0	0
Viral rash
subjects affected / exposed	3 / 183 (1.64%)	0 / 183 (0.00%)	2 / 183 (1.09%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	3	0	2	0	0	0	0	1	0	1
Gastroenteritis rotavirus
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Genital candidiasis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Gianotti-Crosti syndrome
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Gastroenteritis bacterial
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 162 (0.62%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	2 / 183 (1.09%)	21 / 162 (12.96%)	27 / 162 (16.67%)	21 / 169 (12.43%)	7 / 169 (4.14%)
occurrences all number	0	0	0	0	0	2	21	27	24	7
Herpangina
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	4 / 162 (2.47%)	1 / 162 (0.62%)	6 / 169 (3.55%)	2 / 169 (1.18%)
occurrences all number	0	0	0	0	0	1	4	1	6	2
Rotavirus infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	1 / 183 (0.55%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Streptococcal infection
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Herpes simplex
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	1 / 162 (0.62%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Omphalitis
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Oral herpes
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Paronychia
subjects affected / exposed	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	1 / 169 (0.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
Lactose intolerance
subjects affected / exposed	1 / 183 (0.55%)	1 / 183 (0.55%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 183 (0.00%)	0 / 162 (0.00%)	0 / 162 (0.00%)	0 / 169 (0.00%)	0 / 169 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed 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.
[31] - 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.
[32] - 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.
[33] - 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.
[34] - 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.
[35] - 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.
[36] - 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.
[37] - 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.
[38] - 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.
[39] - 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.
[40] - 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.
[41] - 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.
[42] - 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.
[43] - 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.
[44] - 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.
[45] - 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.
[46] - 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.
[47] - 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.
[48] - 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.
[49] - 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.
[50] - 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.
[51] - 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.
[52] - 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

Top of page

Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

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 Given With DTaP Compared to Open-Label DTaP in Healthy Japanese Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Microgram Per Milliliter (mcg/mL) 1 Month After the Infant Series

Primary: Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level Greater Than or Equal to (>=) 0.35 Microgram Per Milliliter (mcg/mL) 1 Month After the Infant Series

Primary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 7 Common Serotypes 1 Month After the Infant Series

Primary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 7 Common Serotypes 1 Month After the Infant Series

Primary: Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Infant Series

Primary: Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 6 Additional Serotypes 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody for 6 Additional Serotypes 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level >=0.35 mcg/mL 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody Level >=0.35 mcg/mL 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) of Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Predefined Antibody Levels for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Antigens 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibodies 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibodies 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibodies 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibodies 1 Month After the Infant Series

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Diphtheria and Tetanus Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibody 1 Month After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Antigen-specific Acellular Pertussis Antibody 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 1 (3 to 6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 1 (3 to 6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 2 (4 to 8 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 2 (4 to 8 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 3 (5 to 10 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Infant Series Dose 3 (5 to 10 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Toddler Dose (12 to 15 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Local Reactions: Toddler Dose (12 to 15 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 1 (3 to 6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 1 (3 to 6 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 2 (4 to 8 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 2 (4 to 8 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 3 (5 to 10 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Infant Series Dose 3 (5 to 10 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Toddler Dose (12 to 15 Months of Age)

Other pre-specified: Percentage of Subjects Reporting Pre-Specified Systemic Events: Toddler Dose (12 to 15 Months of Age)

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 Given With DTaP Compared to Open-Label DTaP in Healthy Japanese Infants