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Clinical Trial Results:
A PHASE 3, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE FORMULATED IN MULTIDOSE VIALS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN HEALTHY INFANTS

Summary
EudraCT number	2012-000482-21
Trial protocol	Outside EU/EEA
Global end of trial date	01 Sep 2014

Results information
Results version number	v1(current)
This version publication date	29 Jun 2016
First version publication date	18 Mar 2015
Other versions

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

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Trial information

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Sponsor protocol code

B4671001

ISRCTN number

US NCT number

NCT01964716

WHO universal trial number (UTN)

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

13 Feb 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Sep 2014

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that the immune response induced by 13-valent pneumococcal conjugate vaccine (13vPnC) with 2-phenoxyethanol in multi-dose vials (MDVs) is noninferior to the immune response induced by 13vPnC without 2-phenoxyethanol in single-dose syringes (SDSs) as measured by serotype-specific immunoglobulin G (IgG) concentrations 1 month after the infant series.

Protection of trial subjects

This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed; in particular, those affording greater protection to the safety of study subjects.

Background therapy

Evidence for comparator

Actual start date of recruitment

09 Jan 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Gambia: 500

Worldwide total number of subjects

500

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)

500

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Total number of subjects screened were 526, out of which 500 were enrolled in the study. The study was conducted in Gambia which started on 09 January 2014 and completed on 01 September 2014.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

13vPnC Multi-dose Vial (MDV)

Arm description

Subjects received three doses of 0.5 milliliter (mL) of 13-valent pneumococcal conjugate vaccine (13vPnC) with 2-phenoxyethanol (2-PE) in MDV intramuscularly at 8, 12 and 16 weeks of age.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine in a multidose vial

Investigational medicinal product code

PF-06414256

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received three doses of 0.5 mL of 13vPnC with 2-PE in MDV intramuscularly at 8, 12 and 16 weeks of age.

13vPnC Single-Dose Syringe (SDS)

Arm description

Subjects received three doses of 0.5 milliliter (mL) of 13-valent pneumococcal conjugate vaccine (13vPnC) without 2-phenoxyethanol (2-PE) in single dose syringe (SDS) intramuscularly at 8, 12 and 16 weeks of age.

Arm type

Active comparator

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine in Single-Dose Syringe

Investigational medicinal product code

PF-05208760

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received three doses of 0.5 mL of 13vPnC without 2-PE in single dose syringe (SDS) intramuscularly at 8, 12 and 16 weeks of age.

Number of subjects in period 1	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Started	250	250
Vaccinated Dose 1	250	250
Vaccinated Dose 2	249	248
Vaccinated Dose 3	247	244
Completed	245	244
Not completed	5	6
Consent withdrawn by subject	2	3
Death	1	-
No longer met eligibility criteria	1	1
Lost to follow-up	1	2

Baseline characteristics

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Reporting group title

13vPnC Multi-dose Vial (MDV)

Reporting group description

Subjects received three doses of 0.5 milliliter (mL) of 13-valent pneumococcal conjugate vaccine (13vPnC) with 2-phenoxyethanol (2-PE) in MDV intramuscularly at 8, 12 and 16 weeks of age.

Reporting group title

13vPnC Single-Dose Syringe (SDS)

Reporting group description

Reporting group values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)	Total
Number of subjects	250	250	500
Age categorical
Units: Subjects
Age continuous
Units: days
arithmetic mean (standard deviation)	57.3 ( 8.6 )	56.9 ( 8.8 )	-
Gender categorical
Units: Subjects
Female	129	130	259
Male	121	120	241

End points

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Reporting group title

13vPnC Multi-dose Vial (MDV)

Reporting group description

Subjects received three doses of 0.5 milliliter (mL) of 13-valent pneumococcal conjugate vaccine (13vPnC) with 2-phenoxyethanol (2-PE) in MDV intramuscularly at 8, 12 and 16 weeks of age.

Reporting group title

13vPnC Single-Dose Syringe (SDS)

Reporting group description

Subject analysis set title

Screened Only

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects who were screened for this study but were not randomized, assessed between signing of informed consent form and before randomization.

Primary: Percentage of Subjects Achieving a Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody concentration Greater Than or Equal To (>=) 0.35 Microgram per Milliliter (mcg/mL) 1 Month After the Infant Series for Each Vaccine Group

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End point title

Percentage of Subjects Achieving a Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody concentration Greater Than or Equal To (>=) 0.35 Microgram per Milliliter (mcg/mL) 1 Month After the Infant Series for Each Vaccine Group

End point description

Percentage of subjects achieving predefined antibody threshold >=0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. Exact 2-sided confidence interval (Clopper and Pearson) based on the observed proportion of subjects. Evaluable immunogenicity population: eligible subjects who received vaccine (as randomized) at all 3 doses, had blood drawn within protocol-specified time frames, had at least 1 valid and determinate assay result for proposed analysis, had no major protocol violations. Here “n”= subjects with valid and determinate IgG concentration to the given serotype.

End point type

Primary

End point timeframe

1 month after the infant series

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	245	244
Units: percentage of subjects
number (confidence interval 95%)
Serotype 1 (n=245,244)	99.2 (97.1 to 99.9)	100 (98.5 to 100)
Serotype 3 (n=245,243)	98.8 (96.5 to 99.7)	99.6 (97.7 to 100)
Serotype 4 (n=245,244)	99.6 (97.7 to 100)	99.6 (97.7 to 100)
Serotype 5 (n=245,244)	95.9 (92.6 to 98)	97.1 (94.2 to 98.8)
Serotype 6A (n=243,244)	96.3 (93.1 to 98.3)	97.5 (94.7 to 99.1)
Serotype 6B (n=245,244)	95.1 (91.6 to 97.4)	95.1 (91.6 to 97.4)
Serotype 7F (n=245,244)	99.6 (97.7 to 100)	100 (98.5 to 100)
Serotype 9V (n=245,244)	98 (95.3 to 99.3)	98.4 (95.9 to 99.6)
Serotype 14 (n=245,244)	97.6 (94.7 to 99.1)	98.4 (95.9 to 99.6)
Serotype 18C (n=245,244)	99.2 (97.1 to 99.9)	98 (95.3 to 99.3)
Serotype 19A (n=245,244)	99.6 (97.7 to 100)	98.8 (96.4 to 99.7)
Serotype 19F (n=245,244)	96.7 (93.7 to 98.6)	97.1 (94.2 to 98.8)
Serotype 23F (n=245,244)	95.9 (92.6 to 98)	95.9 (92.6 to 98)

Serotype 1

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

percent difference

Point estimate

-0.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.4

upper limit

1.2

Notes
[1] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 3

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

percent difference

Point estimate

-0.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.7

upper limit

1.6

Notes
[2] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5%confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 4

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Single-Dose Syringe (SDS) v 13vPnC Multi-dose Vial (MDV)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.3

upper limit

2.4

Notes
[3] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 5

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

percent difference

Point estimate

-1.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-5.4

upper limit

2.8

Notes
[4] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 6A

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

percent difference

Point estimate

-1.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-5.3

upper limit

2.6

Notes
[5] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 6B

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.7

upper limit

4.7

Notes
[6] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 7F

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

percent difference

Point estimate

-0.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.7

upper limit

1.6

Notes
[7] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 9V

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

percent difference

Point estimate

-0.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.8

upper limit

2.8

Notes
[8] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 14

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

percent difference

Point estimate

-0.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.3

upper limit

2.5

Notes
[9] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 18C

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

percent difference

Point estimate

1.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.6

upper limit

4.5

Notes
[10] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 19A

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

percent difference

Point estimate

0.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.6

upper limit

3.6

Notes
[11] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 19F

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

percent difference

Point estimate

-0.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.4

upper limit

3.5

Notes
[12] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Serotype 23F

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.3

upper limit

4.4

Notes
[13] - Non-inferiority for a given antibody was demonstrated if the lower bound of the 2-sided, 97.5% confidence interval, computed using the Chan and Zhang procedure, for the difference in proportions (13vPnC MDV – 13vPnC SDS) was greater than -0.10.

Primary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series for Each Vaccine Group

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End point title

Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series for Each Vaccine Group

End point description

Antibody GMC for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 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. CIs were back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the concentrations. Evaluable immunogenicity population: eligible subjects who received vaccine (as randomized) at all 3 doses, had blood drawn within protocol-specified time frames, had at least 1 valid and determinate assay result for proposed analysis, had no major protocol violations. Here “n”= subjects with valid and determinate IgG concentration to the given serotype.

End point type

Primary

End point timeframe

1 month after the infant series

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	245	244
Units: microgram per milliliter (mcg/mL)
geometric mean (confidence interval 95%)
Serotype 1 (n=245,244)	4.59 (4.11 to 5.12)	4.45 (4.01 to 4.93)
Serotype 3 (n=245,243)	1.38 (1.29 to 1.49)	1.74 (1.62 to 1.87)
Serotype 4 (n=245,244)	5.3 (4.84 to 5.81)	5.28 (4.76 to 5.85)
Serotype 5 (n=245,244)	2 (1.79 to 2.22)	1.98 (1.79 to 2.2)
Serotype 6A (n=243,244)	2.25 (2.02 to 2.5)	2.19 (1.96 to 2.44)
Serotype 6B (n=245,244)	3.42 (2.91 to 4.02)	3.24 (2.77 to 3.78)
Serotype 7F (n=245,244)	3.92 (3.59 to 4.27)	4.18 (3.83 to 4.55)
Serotype 9V (n=245,244)	2.83 (2.56 to 3.13)	2.75 (2.49 to 3.04)
Serotype 14 (n=245,244)	4.78 (4.06 to 5.63)	4.96 (4.27 to 5.77)
Serotype 18C (n=245,244	3.47 (3.17 to 3.79)	2.72 (2.46 to 3)
Serotype 19A (n=245,244)	6.49 (5.7 to 7.38)	6.44 (5.66 to 7.32)
Serotype 19F (n=245,244)	5.19 (4.59 to 5.86)	5 (4.43 to 5.63)
Serotype 23F (n=245,244)	2.61 (2.3 to 2.97)	2.17 (1.92 to 2.46)

Serotype 1

Statistical analysis description

Ratio of GMCs, MDV to SDS, was calculated by back transforming the mean difference between the vaccine groups on the logarithmic scale; CIs for the ratio are back transformations of a confidence interval based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC MDV – 13vPnC SDS).

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.87

upper limit

1.22

Notes
[14] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 3

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

Parameter type

GMC Ratio

Point estimate

0.79

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.71

upper limit

0.9

Notes
[15] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 4

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

Parameter type

GMC Ratio

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.86

upper limit

1.18

Notes
[16] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 5

Statistical analysis description

Comparison groups

13vPnC Single-Dose Syringe (SDS) v 13vPnC Multi-dose Vial (MDV)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

Method

Parameter type

GMC Ratio

Point estimate

1.01

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.85

upper limit

1.19

Notes
[17] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.86

upper limit

1.22

Notes
[18] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 6B

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

Parameter type

GMC Ratio

Point estimate

1.06

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.82

upper limit

1.36

Notes
[19] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

Parameter type

GMC Ratio

Point estimate

0.94

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.82

upper limit

1.08

Notes
[20] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 9V

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

GMC Ratio

Point estimate

1.03

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.87

upper limit

1.21

Notes
[21] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 14

Statistical analysis description

Comparison groups

13vPnC Single-Dose Syringe (SDS) v 13vPnC Multi-dose Vial (MDV)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

GMC Ratio

Point estimate

0.96

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.75

upper limit

1.24

Notes
[22] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 18C

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Parameter type

GMC Ratio

Point estimate

1.28

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.09

upper limit

1.49

Notes
[23] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

Parameter type

GMC Ratio

Point estimate

1.01

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.82

upper limit

1.24

Notes
[24] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 19F

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

Parameter type

GMC Ratio

Point estimate

1.04

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.85

upper limit

1.26

Notes
[25] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Serotype 23F

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

489

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

Parameter type

GMC Ratio

Point estimate

1.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.98

upper limit

1.48

Notes
[26] - Non-inferiority for a given antibody serotype was declared if lower bound of the 2-sided, 97.5% confidence interval for the geometric mean concentration ratio (GMC MDV /GMC SDS) was greater than 0.5 (2-fold criterion).

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 1 in MDV and SDS Group

Top of page

End point title

Number of Subjects Reporting Local Reaction Within 5 Days After Dose 1 in MDV and SDS Group ^[27]

End point description

Local reactions were reported within 5 days (Day 2 to Day 6) using an electronic diary. Tenderness was scaled as Any (tenderness present); Mild (hurt if gently touched; Moderate (hurt if gently touched with crying); Severe (caused limitation of limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.1 to 7.0 cm); Severe (greater than [>] 7.0 cm). Subject may be represented in more than 1 category. Safety population included subects who received at least 1 dose of study vaccine.

End point type

Primary

End point timeframe

Within 5 days after Dose 1 (Day 2 to Day 6) of the infant series

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	248 ^[28]	250
Units: subjects
Redness: Any	1	0
Redness: Mild	1	0
Redness: Moderate	0	0
Redness: Severe	0	0
Swelling: Any	1	0
Swelling: Mild	1	0
Swelling: Moderate	0	0
Swelling: Severe	0	0
Tenderness: Any	42	47
Tenderness: Mild	32	37
Tenderness: Moderate	13	14
Tenderness: Severe	0	0

Notes
[28] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days.

No statistical analyses for this end point

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 2 in MDV and SDS Group

Top of page

End point title

Number of Subjects Reporting Local Reaction Within 5 Days After Dose 2 in MDV and SDS Group ^[29]

End point description

Local reactions were reported within 5 days (Day 2 to Day 6) using an electronic diary. Tenderness was scaled as Any (tenderness present); Mild (hurt if gently touched; Moderate (hurt if gently touched with crying); Severe (caused limitation of limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 cm to 2.0 cm); Moderate (2.1 to 7.0 cm); Severe (>7.0 cm). Subjects may be represented in more than 1 category. Safety population included subjects who received at least 1 dose of study vaccine. Here 'n' = subjects whose response was “Yes” for any day or “No” for all days for specified local reaction.

End point type

Primary

End point timeframe

Within 5 days after Dose 2 (Day 2 to Day 6) of the infant series

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	248 ^[30]	247 ^[31]
Units: subjects
Redness: Any (n=247, 247)	2	0
Redness: Mild (n=247, 247)	2	0
Redness: Moderate (n=247, 247)	0	0
Redness: Severe (n=247, 247)	0	0
Swelling: Any (n=247, 247)	2	0
Swelling: Mild (n=247, 247)	2	0
Swelling: Moderate (n=247, 247)	1	0
Swelling: Severe (n=247, 247)	0	0
Tenderness: Any (n=248, 247)	34	32
Tenderness: Mild (n=248, 247)	27	28
Tenderness: Moderate (n=247, 247)	7	5
Tenderness: Severe (n=247, 247)	0	0

Notes
[30] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days
[31] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days

No statistical analyses for this end point

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 3 in MDV and SDS Group

Top of page

End point title

Number of Subjects Reporting Local Reaction Within 5 Days After Dose 3 in MDV and SDS Group ^[32]

End point description

Local reactions were reported within 5 days (Day 2 to Day 6) using an electronic diary. Tenderness was scaled as Any (tenderness present); Mild (hurt if gently touched; Moderate (hurt if gently touched with crying); Severe (caused limitation of limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 cm to 2.0 cm); Moderate (2.1 to 7.0 cm); Severe (>7.0 cm). Subjects may be represented in more than 1 category. Safety population included subjects who received at least 1 dose of study vaccine.

End point type

Primary

End point timeframe

Within 5 days after Dose 3 (Day 2 to Day 6) of the infant series

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	246 ^[33]	241 ^[34]
Units: subjects
Redness: Any	0	0
Redness: Mild	0	0
Redness: Moderate	0	0
Redness: Severe	0	0
Swelling: Any	0	0
Swelling: Mild	0	0
Swelling: Moderate	0	0
Swelling: Severe	0	0
Tenderness: Any	37	35
Tenderness: Mild	30	32
Tenderness: Moderate	9	4
Tenderness: Severe	0	0

Notes
[33] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days
[34] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days

No statistical analyses for this end point

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 1 in MDV and SDS Group

Top of page

End point title

Number of Subjects Reporting Systemic Events Within 5 Days After Dose 1 in MDV and SDS Group ^[35]

End point description

Systemic events (any fever greater than or equal to [>=] 38.0 degrees Celsius [C], decreased appetite was scaled as; Moderate (decreased oral intake); Severe (refusal to feed). Irritability scaled as; Mild (easily consolable); Moderate (requiring increased attention); Severe (Inconsolable, crying that cannot be comforted). Increased sleep was scale as; mild (increased or prolonged sleeping bouts); Moderate (slightly subdued interfering with daily activity); Severe (Disabling not interested in usual daily activity) and use of antipyretic medication were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population included subjects who received at least 1 dose of study vaccine. Here ‘n’ included subjects whose response was “Yes” for any day or “No” for all days for specified systemic event.

End point type

Primary

End point timeframe

Within 5 days after Dose 1 (Day 2 to Day 6) of infant series

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	249 ^[36]	250
Units: subjects
Fever: >=38.0 degrees C (n=248, 250)	9	7
Fever: >=38.0 but <=39.0 degrees C (n=248, 250)	9	7
Fever: >39.0 but <=40.0 degrees C (n=248, 250)	0	0
Fever: >40.0 degrees C (n=248, 250)	0	0
Decreased appetite: Any (n=248, 250)	17	26
Decreased appetite: Moderate (n=248, 250)	17	26
Decreased appetite: Severe (n=248, 250)	0	0
Irritability: Any (n=249, 250)	103	93
Irritability: Mild (n=249, 250)	86	77
Irritability: Moderate (n=248, 250)	19	17
Irritability: Severe (n=248, 250)	0	0
Increased sleep: Any (n=248, 250)	16	14
Increased sleep: Mild (n=248, 250)	11	10
Increased sleep: Moderate (n=248, 250)	6	4
Increased sleep: Severe (n=248, 250)	0	0
Use of antipyretic medication (n=248, 250)	55	58

Notes
[36] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days

No statistical analyses for this end point

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 2 in MDV and SDS Group

Top of page

End point title

Number of Subjects Reporting Systemic Events Within 5 Days After Dose 2 in MDV and SDS Group ^[37]

End point description

Systemic events (>= 38.0 degrees C, decreased appetite was scaled as; Moderate (decreased oral intake); Severe (refusal to feed). Irritability scaled as; Mild (easily consolable); Moderate (requiring increased attention); Severe (Inconsolable, crying that cannot be comforted). Increased sleep was scale as; mild (increased or prolonged sleeping bouts); Moderate (slightly subdued interfering with daily activity); Severe (Disabling not interested in usual daily activity) and use of antipyretic medication were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population included subjects who received at least 1 dose of study vaccine. Here ‘n’ included subjects whose response was “Yes” for any day or “No” for all days for specified systemic event.

End point type

Primary

End point timeframe

Within 5 days after Dose 2 (Day 2 to Day 6) of infant series

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	248 ^[38]	247 ^[39]
Units: subjects
Fever: >=38.0 degrees C (n=247, 247)	7	7
Fever: >=38.0 but <=39.0 degrees C (n=247, 247)	7	7
Fever: >39.0 but <=40.0 degrees C (n=247, 247)	1	0
Fever: >40.0 degrees C (n=247, 247)	0	0
Decreased appetite: Any(n=247, 247)	28	18
Decreased appetite: Moderate (n=247, 247)	28	18
Decreased appetite: Severe (n=247, 247)	0	0
Irritability: Any (n=248, 247)	93	83
Irritability: Mild (n=248, 247)	75	67
Irritability: Moderate (n=247, 247)	23	17
Irritability: Severe (n=247, 247)	0	3
Increased sleep: Any (n=247, 247)	24	14
Increased sleep: Mild (n=247, 247)	20	12
Increased sleep: Moderate (n=247, 247)	4	1
Increased sleep: Severe (n=247, 247)	0	1
Use of antipyretic medication (n=248, 247)	46	43

Notes
[38] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days
[39] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days

No statistical analyses for this end point

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 3 in MDV and SDS Group

Top of page

End point title

Number of Subjects Reporting Systemic Events Within 5 Days After Dose 3 in MDV and SDS Group ^[40]

End point description

Systemic events (any fever >= 38.0 degrees C, decreased appetite was scaled as; Moderate (decreased oral intake); Severe (refusal to feed). Irritability scaled as; Mild (easily consolable); Moderate (requiring increased attention); Severe (Inconsolable, crying that cannot be comforted). Increased sleep was scale as; mild (increased or prolonged sleeping bouts); Moderate (slightly subdued interfering with daily activity); Severe (Disabling not interested in usual daily activity) and use of antipyretic medication were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population included subjects who received at least 1 dose of study vaccine. Here ‘n’ included subjects whose response was “Yes” for any day or “No” for all days for specified systemic event.

End point type

Primary

End point timeframe

Within 5 days after Dose 3 (Day 2 to Day 6) of infant series

Notes
[40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	246 ^[41]	243 ^[42]
Units: subjects
Fever: >=38.0 degrees C (n=246, 241)	3	8
Fever: >=38.0 but <=39.0 degrees C (n=246, 241)	3	7
Fever: >39.0 but <=40.0 degrees C (n=246, 241)	0	1
Fever: >40.0 degrees C (n=246, 241)	0	0
Decreased appetite: Any (n=246, 242)	24	20
Decreased appetite: Moderate (n=246, 242)	24	19
Decreased appetite: Severe (n=246, 241)	0	1
Irritability: Any (n=246, 243)	83	92
Irritability: Mild (n=246, 242)	71	74
Irritability: Moderate (n=246, 242)	15	18
Irritability: Severe (n=246, 241)	1	5
Increased sleep: Any (n=246, 241)	12	12
Increased sleep: Mild (n=246, 241)	10	11
Increased sleep: Moderate (n=246, 241)	2	1
Increased sleep: Severe (n=246, 241)	1	0
Use of antipyretic medication (n=246, 241)	34	36

Notes
[41] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days
[42] - ‘N’ (number of subjects analyzed)= subjects whose response=Yes for any day or No for all days

No statistical analyses for this end point

Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Infant Series

Top of page

End point title

Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Infant Series ^[43]

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 to 42 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. Safety population included all subjects who received at least 1 dose of study vaccine.

End point type

Primary

End point timeframe

Dose 1 up to 28 to 42 Days after Dose 3

Notes
[43] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	250	250
Units: subjects
AEs	123	127
SAEs	1	0

No statistical analyses for this end point

Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Prior to Dose 1

Top of page

End point title

Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Prior to Dose 1 ^[44]

End point description

An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Adverse events were also reported in subjects who provided consent but were not randomized in this study. The data of these subjects has been reported under ‘Screened Only’ arm. Safety population included subjects who received at least 1 dose of study vaccine.

End point type

Primary

End point timeframe

Informed consent up to Dose 1

Notes
[44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not planned for numbers of subjects with local reactions or systemic events.

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)	Screened Only
Number of subjects analysed	250	250	26
Units: subjects
AEs	2	0	9
SAEs	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving a Serotype-Specific Opsonophagocytic Activity (OPA) Titer >= lower limit of quantitation (LLOQ) 1 Month After Infant Series

Top of page

End point title

Percentage of Subjects Achieving a Serotype-Specific Opsonophagocytic Activity (OPA) Titer >= lower limit of quantitation (LLOQ) 1 Month After Infant Series

End point description

Percentage of subjects achieving OPA Titer >= lower limit of quantitation (LLOQ) along with 95% CI for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Exact 2-sided confidence interval (Clopper and Pearson) based on the observed proportion of subjects. Here “n”= Number of subjects with an antibody titer >= LLOQ for the given serotype. Evaluable immunogenicity population: subjects who received vaccine (randomized) at all 3 doses, had blood drawn within protocol-specified time frames, had at least 1 valid and determinate assay result for proposed analysis, had no major protocol violations. OPA analysis was performed in a subset of randomly selected subjects from each group.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	160	160
Units: percentage of subjects
number (confidence interval 95%)
Serotype 1 (n=159,160)	71.7 (64 to 78.5)	79.4 (72.3 to 85.4)
Serotype 3 (n=160,160)	98.8 (95.6 to 99.8)	100 (97.7 to 100)
Serotype 4 (n=159,159)	100 (97.7 to 100)	100 (97.7 to 100)
Serotype 5 (n=160,159)	83.1 (76.4 to 88.6)	85.5 (79.1 to 90.6)
Serotype 6A (n=160,160)	99.4 (96.6 to 100)	99.4 (96.6 to 100)
Serotype 6B (n=156,155)	96.8 (92.7 to 99)	96.8 (92.6 to 98.9)
Serotype 7F (n=159,160)	100 (97.7 to 100)	100 (97.7 to 100)
Serotype 9V (n=158,160)	79.7 (72.6 to 85.7)	75 (67.6 to 81.5)
Serotype 14 (n=157,160)	81.5 (74.6 to 87.3)	89.4 (83.5 to 93.7)
Serotype 18C (n=159,160)	99.4 (96.5 to 100)	99.4 (96.6 to 100)
Serotype 19A (n=160,160)	95.6 (91.2 to 98.2)	97.5 (93.7 to 99.3)
Serotype 19F (n=158,159)	93.7 (88.7 to 96.9)	94.3 (89.5 to 97.4)
Serotype 23F (n=159,160)	96.2 (92 to 98.6)	97.5 (93.7 to 99.3)

Serotype 1

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-17.2

upper limit

1.9

Serotype 3

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Single-Dose Syringe (SDS) v 13vPnC Multi-dose Vial (MDV)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

1.1

Serotype 4

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

2.3

Serotype 5

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-2.4

Confidence interval

level

95%

sides

2-sided

lower limit

-10.6

upper limit

5.7

Serotype 6A

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

2.8

Serotype 6B

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

4.6

Serotype 7F

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

2.3

Serotype 9V

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

4.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.5

upper limit

14.1

Serotype 14

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-15.8

upper limit

Serotype 18C

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

2.9

Serotype 19A

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.6

upper limit

2.4

Serotype 19F

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

4.9

Serotype 23F

Statistical analysis description

Exact 2-sided confidence interval (based on Chan and Zhang) for the difference in proportions, 13vPnC MDV – 13vPnC SDS, expressed as a percentage was analyzed.

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

percent difference

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-5.8

upper limit

Secondary: Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After the Infant Series

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End point title

Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After the Infant Series

End point description

Antibody geometric mean titers as measured by OPA assay for the 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F 9V, 14, 18C, 19A, 19F and 23F) are presented. GMTs were calculated using all subjects with available data for the specified blood draw. CIs were back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the titers. Evaluable immunogenicity population: subjects who received vaccine (randomized) at all 3 doses, had blood drawn within protocol-specified time frames, had at least 1 valid and determinate assay result for proposed analysis, had no major protocol violations. OPA analysis was performed in a subset of randomly selected subjects from each group. Here “n”= subjects evaluable =specified category.

End point type

Secondary

End point timeframe

1 month after the infant series

End point values	13vPnC Multi-dose Vial (MDV)	13vPnC Single-Dose Syringe (SDS)
Number of subjects analysed	160	160
Units: titer
geometric mean (confidence interval 95%)
Serotype 1 (n=159,160)	48 (39 to 58)	52 (43.2 to 62.6)
Serotype 3 (n=160,160)	97 (87.3 to 108.8)	122 (110.1 to 135.7)
Serotype 4 (n=159,159)	1666 (1412.3 to 1966.3)	1492 (1285.2 to 1732.3)
Serotype 5 (n=160,159)	79 (67.7 to 92.4)	80 (69.1 to 92.6)
Serotype 6A (n=160,160)	1690 (1460.5 to 1955.9)	1968 (1698.5 to 2279.3)
Serotype 6B (n=156,155)	1990 (1611.7 to 2456.9)	2014 (1639.1 to 2475.4)
Serotype 7F (n=159,160)	2891 (2565.4 to 3258.5)	3450 (3014.7 to 3947.9)
Serotype 9V (n=158,160)	709 (600.5 to 836.2)	706 (597 to 835.3)
Serotype 14 (n=157,160)	567 (415.4 to 773.5)	786 (607.8 to 1015.3)
Serotype 18C (n=159,160)	2792 (2387.5 to 3264.8)	1605 (1352 to 1904.4)
Serotype 19A (n=160,160)	305 (256.2 to 362.9)	329 (284.8 to 379.8)
Serotype 19F (n=158,159)	430 (357.6 to 517.1)	470 (391.4 to 565.3)
Serotype 23F (n=159,160)	918 (729 to 1156.4)	998 (810.6 to 1229.6)

Serotype 1

Statistical analysis description

Ratio of GMTs, MDV to SDS, was calculated by back transforming the mean difference between the vaccine groups on the logarithmic scale. CIs for the ratio were back transformations of a confidence interval based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC MDV – 13vPnC SDS).

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.2

Serotype 3

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

0.93

Serotype 4

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.39

Serotype 5

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

1.22

Serotype 6A

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.06

Serotype 6B

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.33

Serotype 7F

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

Serotype 9V

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.27

Serotype 14

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.08

Serotype 18C

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

2.19

Serotype 19A

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.16

Serotype 19F

Statistical analysis description

Comparison groups

13vPnC Multi-dose Vial (MDV) v 13vPnC Single-Dose Syringe (SDS)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.18

Serotype 23F

Statistical analysis description

Comparison groups

13vPnC Single-Dose Syringe (SDS) v 13vPnC Multi-dose Vial (MDV)

Number of subjects included in analysis

320

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.25

Adverse events

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Timeframe for reporting adverse events

Adverse events (AEs)/serious AEs (SAEs): recorded from signing of informed consent form to 28 to 42 days after dose 3. Pre-specified AEs were recorded in an electronic diary: local reactions, systemic events (Day 2 to Day 6 after each vaccination).

Adverse event reporting additional description

SAEs, AEs grouped by system organ class and summarized. AEs included AEs collected in electronic diary (local, systemic reactions; systematic assessment), events collected on case report form at each visit (non-systematic assessment). AEs also reported in subjects who provided consent but were not randomized (reported under ‘Screened Only’ arm).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

13vPnC MDV: Informed Consent to Dose 1

Reporting group description

Subjects who were randomized to receive 13vPnC (PF-06414256) MDV at 8, 12, and 16 weeks of age, assessed between signing of informed consent and before Dose 1.

Reporting group title

13vPnC SDS: Informed Consent to Dose 1

Reporting group description

Subjects who were randomized to receive 13vPnC (PF-05208760) SDS at 8, 12, and 16 weeks of age, assessed between signing of informed consent and before Dose 1.

Reporting group title

13vPnC MDV: After Dose 1

Reporting group description

Subjects who received single 0.5 mL dose of 13vPnC (PF-06414256) using MDV intramuscularly into the anterolateral thigh muscle of the left leg at 8 weeks of age, assessed after Dose 1 and before Dose 2.

Reporting group title

13vPnC SDS: After Dose 1

Reporting group description

Subjects who received single 0.5 mL dose of 13vPnC (PF-05208760) using SDS intramuscularly into the anterolateral thigh muscle of the left leg at 8 weeks of age, assessed after Dose 1 and before Dose 2.

Reporting group title

13vPnC MDV: After Dose 2

Reporting group description

Subjects who received two 0.5 mL doses of 13vPnC (PF-06414256) using MDV intramuscularly into the anterolateral thigh muscle of the left leg 8, 12 weeks of age, assessed after Dose 2 and before Dose 3.

Reporting group title

13vPnC SDS: After Dose 2

Reporting group description

Subjects who received two 0.5 mL doses of 13vPnC (PF-05208760) using SDS intramuscularly into the anterolateral thigh muscle of the left leg 8, 12 weeks of age, assessed after Dose 2 and before Dose 3.

Reporting group title

13vPnC MDV: After Dose 3

Reporting group description

Subjects who received all three 0.5mL doses of 13vPnC (PF-06414256) using MDV intramuscularly into the anterolateral thigh muscle of the left leg at 8 weeks of age, assessed after Dose 3 and up to blood draw at 4 weeks.

Reporting group title

13vPnC SDS: After Dose 3

Reporting group description

Subjects who received all three 0.5mL doses of 13vPnC (PF-05208760) using SDS intramuscularly into the anterolateral thigh muscle of the left leg at 8 weeks of age, assessed after Dose 3 and up to blood draw at 4 weeks.

Reporting group title

Screened Only

Reporting group description

Subjects who were screened for this study but were not randomized, assessed between signing of informed consent form and before randomization.

Serious adverse events	13vPnC MDV: Informed Consent to Dose 1	13vPnC SDS: Informed Consent to Dose 1	13vPnC MDV: After Dose 1	13vPnC SDS: After Dose 1	13vPnC MDV: After Dose 2	13vPnC SDS: After Dose 2	13vPnC MDV: After Dose 3	13vPnC SDS: After Dose 3	Screened Only
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	1	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Sudden infant death syndrome
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0

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

Non-serious adverse events	13vPnC MDV: Informed Consent to Dose 1	13vPnC SDS: Informed Consent to Dose 1	13vPnC MDV: After Dose 1	13vPnC SDS: After Dose 1	13vPnC MDV: After Dose 2	13vPnC SDS: After Dose 2	13vPnC MDV: After Dose 3	13vPnC SDS: After Dose 3	Screened Only
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 250 (0.80%)	0 / 250 (0.00%)	113 / 250 (45.20%)	107 / 250 (42.80%)	114 / 249 (45.78%)	99 / 248 (39.92%)	97 / 247 (39.27%)	102 / 244 (41.80%)	9 / 26 (34.62%)
Injury, poisoning and procedural complications
Burns first degrees
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Contusion
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Fall
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Congenital, familial and genetic disorders
Heart disease congenital
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	0	1
Pregnancy, puerperium and perinatal conditions
Umbilical granuloma
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	2 / 250 (0.80%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
General disorders and administration site conditions
Decreased appetite: Any
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	0 / 250 (0.00%)	0 / 250 (0.00%)	17 / 248 (6.85%)	26 / 250 (10.40%)	28 / 247 (11.34%)	18 / 247 (7.29%)	24 / 246 (9.76%)	20 / 242 (8.26%)	0 / 26 (0.00%)
occurrences all number	0	0	17	26	28	18	24	20	0
Decreased appetite: Moderate
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	0 / 250 (0.00%)	0 / 250 (0.00%)	17 / 248 (6.85%)	26 / 250 (10.40%)	28 / 247 (11.34%)	18 / 247 (7.29%)	24 / 246 (9.76%)	19 / 242 (7.85%)	0 / 26 (0.00%)
occurrences all number	0	0	17	26	28	18	24	19	0
Decreased appetite: Severe
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 248 (0.00%)	0 / 250 (0.00%)	0 / 247 (0.00%)	0 / 247 (0.00%)	0 / 246 (0.00%)	1 / 241 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Fever: >=38.0 but <=39.0 degrees C
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	0 / 250 (0.00%)	0 / 250 (0.00%)	9 / 248 (3.63%)	7 / 250 (2.80%)	7 / 247 (2.83%)	7 / 247 (2.83%)	3 / 246 (1.22%)	7 / 241 (2.90%)	0 / 26 (0.00%)
occurrences all number	0	0	9	7	7	7	3	7	0
Fever: >=38.0 degrees C
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	0 / 250 (0.00%)	0 / 250 (0.00%)	9 / 248 (3.63%)	7 / 250 (2.80%)	7 / 247 (2.83%)	7 / 247 (2.83%)	3 / 246 (1.22%)	8 / 241 (3.32%)	0 / 26 (0.00%)
occurrences all number	0	0	9	7	7	7	3	8	0
Fever: >39.0 but <=40.0 degrees C
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 248 (0.00%)	0 / 250 (0.00%)	1 / 247 (0.40%)	0 / 247 (0.00%)	0 / 246 (0.00%)	1 / 241 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0
Increased sleep: Any
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	0 / 250 (0.00%)	0 / 250 (0.00%)	16 / 248 (6.45%)	14 / 250 (5.60%)	24 / 247 (9.72%)	14 / 247 (5.67%)	12 / 246 (4.88%)	12 / 241 (4.98%)	0 / 26 (0.00%)
occurrences all number	0	0	16	14	24	14	12	12	0
Increased sleep: Mild
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[8]	0 / 250 (0.00%)	0 / 250 (0.00%)	11 / 248 (4.44%)	10 / 250 (4.00%)	20 / 247 (8.10%)	12 / 247 (4.86%)	10 / 246 (4.07%)	11 / 241 (4.56%)	0 / 26 (0.00%)
occurrences all number	0	0	11	10	20	12	10	11	0
Increased sleep: Moderate
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative assessment type: Systematic
subjects affected / exposed ^[9]	0 / 250 (0.00%)	0 / 250 (0.00%)	6 / 248 (2.42%)	4 / 250 (1.60%)	4 / 247 (1.62%)	1 / 247 (0.40%)	2 / 246 (0.81%)	1 / 241 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	6	4	4	1	2	1	0
Increased sleep: Severe
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[10]	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 248 (0.00%)	0 / 250 (0.00%)	0 / 247 (0.00%)	1 / 247 (0.40%)	1 / 246 (0.41%)	0 / 241 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0
Irritability: Any
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[11]	0 / 250 (0.00%)	0 / 250 (0.00%)	103 / 249 (41.37%)	93 / 250 (37.20%)	93 / 248 (37.50%)	83 / 247 (33.60%)	83 / 246 (33.74%)	92 / 243 (37.86%)	0 / 26 (0.00%)
occurrences all number	0	0	103	93	93	83	83	92	0
Irritability: Mild
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[12]	0 / 250 (0.00%)	0 / 250 (0.00%)	86 / 249 (34.54%)	77 / 250 (30.80%)	75 / 248 (30.24%)	67 / 247 (27.13%)	71 / 246 (28.86%)	74 / 242 (30.58%)	0 / 26 (0.00%)
occurrences all number	0	0	86	77	75	67	71	74	0
Irritability: Moderate
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[13]	0 / 250 (0.00%)	0 / 250 (0.00%)	19 / 248 (7.66%)	17 / 250 (6.80%)	23 / 247 (9.31%)	17 / 247 (6.88%)	15 / 246 (6.10%)	18 / 242 (7.44%)	0 / 26 (0.00%)
occurrences all number	0	0	19	17	23	17	15	18	0
Irritability: Severe
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[14]	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 248 (0.00%)	0 / 250 (0.00%)	0 / 247 (0.00%)	3 / 247 (1.21%)	1 / 246 (0.41%)	5 / 241 (2.07%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	3	1	5	0
Pyrexia
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	2 / 250 (0.80%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	2	0	0	1	1	0
Ulcer
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	1 / 248 (0.40%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Vaccination site swelling
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0
Vomiting
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	3 / 250 (1.20%)	1 / 250 (0.40%)	0 / 249 (0.00%)	1 / 248 (0.40%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	3	1	0	1	1	0	0
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Cough
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	2 / 250 (0.80%)	2 / 250 (0.80%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	2	2	0	0	0	0	0
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	1 / 249 (0.40%)	1 / 248 (0.40%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	1	1	0	0	0
Dermatitis
subjects affected / exposed	1 / 250 (0.40%)	0 / 250 (0.00%)	8 / 250 (3.20%)	12 / 250 (4.80%)	5 / 249 (2.01%)	7 / 248 (2.82%)	2 / 247 (0.81%)	6 / 244 (2.46%)	0 / 26 (0.00%)
occurrences all number	1	0	8	12	5	7	2	6	0
Dermatitis atopic
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	1 / 248 (0.40%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Dermatitis diaper
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	2 / 244 (0.82%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	1	2	0
Rash papular
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	1 / 248 (0.40%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Redness: Any
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[15]	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 248 (0.40%)	0 / 250 (0.00%)	2 / 247 (0.81%)	0 / 247 (0.00%)	0 / 246 (0.00%)	0 / 241 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	2	0	0	0	0
Redness: Mild
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[16]	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 248 (0.40%)	0 / 250 (0.00%)	2 / 247 (0.81%)	0 / 247 (0.00%)	0 / 246 (0.00%)	0 / 241 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	2	0	0	0	0
Skin ulcer
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Swelling: Any
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[17]	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 248 (0.40%)	0 / 250 (0.00%)	2 / 247 (0.81%)	0 / 247 (0.00%)	0 / 246 (0.00%)	0 / 241 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	2	0	0	0	0
Swelling: Mild
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[18]	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 248 (0.40%)	0 / 250 (0.00%)	2 / 247 (0.81%)	0 / 247 (0.00%)	0 / 246 (0.00%)	0 / 241 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	2	0	0	0	0
Swelling: Moderate
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[19]	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 248 (0.00%)	0 / 250 (0.00%)	0 / 247 (0.00%)	1 / 247 (0.40%)	0 / 246 (0.00%)	0 / 241 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Tenderness: Any
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[20]	0 / 250 (0.00%)	0 / 250 (0.00%)	42 / 248 (16.94%)	47 / 250 (18.80%)	34 / 248 (13.71%)	32 / 247 (12.96%)	37 / 246 (15.04%)	35 / 241 (14.52%)	0 / 26 (0.00%)
occurrences all number	0	0	42	47	34	32	37	35	0
Tenderness: Mild
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[21]	0 / 250 (0.00%)	0 / 250 (0.00%)	32 / 248 (12.90%)	37 / 250 (14.80%)	27 / 248 (10.89%)	28 / 247 (11.34%)	30 / 246 (12.20%)	32 / 241 (13.28%)	0 / 26 (0.00%)
occurrences all number	0	0	32	37	27	28	30	32	0
Tenderness: Moderate
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[22]	0 / 250 (0.00%)	0 / 250 (0.00%)	13 / 248 (5.24%)	14 / 250 (5.60%)	7 / 247 (2.83%)	5 / 247 (2.02%)	9 / 246 (3.66%)	4 / 241 (1.66%)	0 / 26 (0.00%)
occurrences all number	0	0	13	14	7	5	9	4	0
Musculoskeletal and connective tissue disorders
Growth retardation
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	0	1
Musculoskeletal pain
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Infections and infestations
Atypical pneumonia
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0
Breast abscess
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0
Bronchopneumonia
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	1 / 248 (0.40%)	1 / 247 (0.40%)	4 / 244 (1.64%)	2 / 26 (7.69%)
occurrences all number	0	0	0	0	0	1	1	5	2
Chest wall abscess
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Conjunctivitis
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	3 / 250 (1.20%)	3 / 250 (1.20%)	3 / 249 (1.20%)	1 / 248 (0.40%)	4 / 247 (1.62%)	3 / 244 (1.23%)	1 / 26 (3.85%)
occurrences all number	0	0	3	3	3	1	4	3	1
Dysentery
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Furuncle
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	3 / 247 (1.21%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0
Gastroenteritis
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	1	0	0	1	0
Gastroenteritis viral
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Impetigo
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	2 / 247 (0.81%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0
Injection site abscess
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Otitis media
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	2 / 250 (0.80%)	2 / 249 (0.80%)	1 / 248 (0.40%)	3 / 247 (1.21%)	2 / 244 (0.82%)	0 / 26 (0.00%)
occurrences all number	0	0	1	2	2	1	3	2	0
Otitis media acute
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	2 / 244 (0.82%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Rash pustular
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 250 (0.00%)	1 / 249 (0.40%)	3 / 248 (1.21%)	6 / 247 (2.43%)	3 / 244 (1.23%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	1	3	6	3	0
Tinea capitis
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	4 / 250 (1.60%)	3 / 250 (1.20%)	3 / 249 (1.20%)	1 / 248 (0.40%)	2 / 247 (0.81%)	1 / 244 (0.41%)	0 / 26 (0.00%)
occurrences all number	0	0	4	3	3	1	2	1	0
Tinea faciei
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 249 (0.40%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Tinea infection
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0
Tinea versicolour
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	1 / 250 (0.40%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 250 (0.40%)	0 / 250 (0.00%)	27 / 250 (10.80%)	17 / 250 (6.80%)	17 / 249 (6.83%)	10 / 248 (4.03%)	19 / 247 (7.69%)	25 / 244 (10.25%)	0 / 26 (0.00%)
occurrences all number	1	0	28	17	17	10	19	25	0
Urinary tract infection
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	0 / 244 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	0	1
Varicella
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	1 / 247 (0.40%)	0 / 244 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Viral diarrhoea
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	6 / 250 (2.40%)	10 / 250 (4.00%)	8 / 249 (3.21%)	10 / 248 (4.03%)	5 / 247 (2.02%)	10 / 244 (4.10%)	0 / 26 (0.00%)
occurrences all number	0	0	6	10	8	10	5	10	0
Viral infection
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	3 / 250 (1.20%)	1 / 250 (0.40%)	1 / 249 (0.40%)	3 / 248 (1.21%)	0 / 247 (0.00%)	4 / 244 (1.64%)	0 / 26 (0.00%)
occurrences all number	0	0	3	1	1	3	0	4	0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 250 (0.00%)	0 / 249 (0.00%)	0 / 248 (0.00%)	0 / 247 (0.00%)	1 / 244 (0.41%)	3 / 26 (11.54%)
occurrences all number	0	0	0	0	0	0	0	1	3

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.

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A PHASE 3, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE FORMULATED IN MULTIDOSE VIALS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN HEALTHY INFANTS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving a Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody concentration Greater Than or Equal To (>=) 0.35 Microgram per Milliliter (mcg/mL) 1 Month After the Infant Series for Each Vaccine Group

Primary: Percentage of Subjects Achieving a Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody concentration Greater Than or Equal To (>=) 0.35 Microgram per Milliliter (mcg/mL) 1 Month After the Infant Series for Each Vaccine Group

Primary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series for Each Vaccine Group

Primary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Month After the Infant Series for Each Vaccine Group

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 1 in MDV and SDS Group

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 1 in MDV and SDS Group

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 2 in MDV and SDS Group

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 2 in MDV and SDS Group

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 3 in MDV and SDS Group

Primary: Number of Subjects Reporting Local Reaction Within 5 Days After Dose 3 in MDV and SDS Group

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 1 in MDV and SDS Group

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 1 in MDV and SDS Group

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 2 in MDV and SDS Group

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 2 in MDV and SDS Group

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 3 in MDV and SDS Group

Primary: Number of Subjects Reporting Systemic Events Within 5 Days After Dose 3 in MDV and SDS Group

Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Infant Series

Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) in the Infant Series

Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Prior to Dose 1

Primary: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) Prior to Dose 1

Secondary: Percentage of Subjects Achieving a Serotype-Specific Opsonophagocytic Activity (OPA) Titer >= lower limit of quantitation (LLOQ) 1 Month After Infant Series

Secondary: Percentage of Subjects Achieving a Serotype-Specific Opsonophagocytic Activity (OPA) Titer >= lower limit of quantitation (LLOQ) 1 Month After Infant Series

Secondary: Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After the Infant Series

Secondary: Serotype-Specific Opsonophagocytic Activity (OPA) Geometric Mean Titer (GMT) 1 Month After the Infant Series

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A PHASE 3, RANDOMIZED, OPEN-LABEL TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE FORMULATED IN MULTIDOSE VIALS GIVEN WITH ROUTINE PEDIATRIC VACCINATIONS IN HEALTHY INFANTS