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Clinical Trial Results:
A Phase 3, Randomized, Active-Controlled Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) Compared with a 7-Valent Pneumococcal Conjugate Vaccine (7vPnC) in Healthy Infants in China.

Summary
EudraCT number	2014-004953-14
Trial protocol	Outside EU/EEA
Global end of trial date	21 Apr 2014

Results information
Results version number	v1(current)
This version publication date	29 Jun 2016
First version publication date	02 Aug 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

B1851015

ISRCTN number

US NCT number

NCT01692886

WHO universal trial number (UTN)

Other trial identifiers

Alias: 6096A1-3019-CN

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

Clinical Trials.gov Call Center, Pfizer Inc., 001 800-718-1021, clinicaltrials.gov_inquiries@pfizer.com

Scientific contact

Clinical Trials.gov Call Center, Pfizer Inc., 001 800-718-1021, 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

06 Feb 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Apr 2014

Was the trial ended prematurely?

Main objective of the trial

1)To demonstrate that the immune responses to the 13 pneumococcal serotypes induced by 13vPnC in a 3-, 4-, 5-, and 12-month schedule (Group 2) are non inferior to the immune responses induced by 7vPnC in a 3-, 4-, 5-, and 12-month schedule (Group 1) when measured 1 month after the infant series. 2)To demonstrate that the immune responses to the 13 pneumococcal serotypes induced by 13vPnC in a 2-, 4-, 6-, and 12-month schedule (Group 3) are noninferior to the immune responses induced by 7vPnC in a 3-, 4-, 5-, and 12-month schedule (Group 1) when measured 1 month after the infant series. 3) To evaluate the acceptability of the safety profile of 13vPnC as measured by the incidence rates of local reactions, systemic events, and adverse events (AEs).

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Sep 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

China: 1674

Worldwide total number of subjects

1674

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)

1674

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

This phase 3, parallel-group, randomized, active-controlled study randomized 1674 subjects in 5 study centers in China (one coordinating and 4 satellite sites). Subjects were randomized to 1 of 4 groups and were vaccinated with 7vPnC (7-valent pneumococcal conjugate vaccine) or 13vPnC (13-valent pneumococcal conjugate vaccine).

Screening details

Healthy infants (aged 42 to 77 days [approximately 2 months] at the time of enrollment) as determined by medical history, physical examination, and judgment of the investigator were enrolled and vaccinated in this study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

Vaccine allocation for subjects in Groups 1 and 2 were blinded to both the subject’s parent/guardian(s) and the investigator. Vaccine allocations for subjects in Groups 3 and 4 were open to the subject's parent/guardian(s) and the investigator.

Are arms mutually exclusive

Yes

7vPnC Group 1

Arm description

Subjects received 7vPnC vaccine administered at 3, 4, 5, and 12 months of age.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Prevenar

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received single 0.5 mL (milliliter) of 7vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

13vPnC Group 2

Arm description

Subjects received 13vPnC vaccine administered at 3, 4, 5, and 12 months of age.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Prevenar 13

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received single dose 0.5 mL of 13vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

13vPnC Group 3

Arm description

Subjects received 13vPnC vaccine administered at 2, 4, 6, and 12 months of age.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Prevenar 13

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received single 0.5 mL of 13vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

13vPnC Group 4

Arm description

Subjects received 13vPnC vaccine administered at 3, 5, and 12 months of age.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Prevenar 13

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received single dose 0.5 mL of 13vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

Number of subjects in period 1	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Started	478	478	479	239
Treated	472	472	476	234
Completed	417	433	434	221
Not completed	61	45	45	18
Consent withdrawn by subject	29	18	19	8
Does not meet entrance criteria	1	-	1	-
Protocol violation	-	-	1	-
Not specified	23	16	10	7
Adverse event	7	8	7	2
Lost to follow-up	1	3	7	1

Baseline characteristics

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Reporting group title

7vPnC Group 1

Reporting group description

Subjects received 7vPnC vaccine administered at 3, 4, 5, and 12 months of age.

Reporting group title

13vPnC Group 2

Reporting group description

Subjects received 13vPnC vaccine administered at 3, 4, 5, and 12 months of age.

Reporting group title

13vPnC Group 3

Reporting group description

Subjects received 13vPnC vaccine administered at 2, 4, 6, and 12 months of age.

Reporting group title

13vPnC Group 4

Reporting group description

Subjects received 13vPnC vaccine administered at 3, 5, and 12 months of age.

Reporting group values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4	Total
Number of subjects	478	478	479	239	1674
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	1.97 ( 0.343 )	1.96 ( 0.339 )	2 ( 0.334 )	1.99 ( 0.349 )	-
Gender categorical
Units: Subjects
Female	213	229	226	113	781
Male	265	249	253	126	893

End points

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Reporting group title

7vPnC Group 1

Reporting group description

Subjects received 7vPnC vaccine administered at 3, 4, 5, and 12 months of age.

Reporting group title

13vPnC Group 2

Reporting group description

Subjects received 13vPnC vaccine administered at 3, 4, 5, and 12 months of age.

Reporting group title

13vPnC Group 3

Reporting group description

Subjects received 13vPnC vaccine administered at 2, 4, 6, and 12 months of age.

Reporting group title

13vPnC Group 4

Reporting group description

Subjects received 13vPnC vaccine administered at 3, 5, and 12 months of age.

Primary: Percentage of Subjects Achieving a Pneumococcal Immunoglobin G(IgG) Antibody Concentration Greater Than or Equal to (≥)0.35 microgram per milliliter (µg/mL) 1 Month After the Infant Series, 13vPnC Group 2 versus (vs) 7vPnC Group 1

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End point title

Percentage of Subjects Achieving a Pneumococcal Immunoglobin G(IgG) Antibody Concentration Greater Than or Equal to (≥)0.35 microgram per milliliter (µg/mL) 1 Month After the Infant Series, 13vPnC Group 2 versus (vs) 7vPnC Group 1 ^[1]

End point description

The proportion of subjects achieving serotype-specific immunoglobulin G (IgG) concentrations greater than and equal to (≥)0.35 microgram per milliliter (µg/mL) 1 month after the infant series is presented for all common serotypes and 6 additional serotypes. For immunogenicity evaluation, 3 blood samples (approximately 5 mL) were collected during the course of the study. For subjects in Groups 1 and 2, blood samples were collected at the 6-, 12-, and 13-month visits. In the below table 'N' represents the number of subjects with a determinate IgG antibody concentration to the given serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required timeframe, received no prohibited vaccines and had no major protocol deviation.

End point type

Primary

End point timeframe

1 month after the infant series (6 Months of age)

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	446	446
Units: Percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=444, 445)	99.8 (98.8 to 100)	100 (99.2 to 100)
7vPnC - Serotype 6B (N=441, 444)	96.1 (93.9 to 97.7)	93.2 (90.5 to 95.4)
7vPnC - Serotype 9V (N=446, 445)	99.8 (98.8 to 100)	99.8 (98.8 to 100)
7vPnC - Serotype 14 (N=446, 445)	100 (99.2 to 100)	99.6 (98.4 to 99.9)
7vPnC - Serotype 18C (N=446,445)	99.1 (97.7 to 99.8)	98.6 (97.1 to 99.5)
7vPnC - Serotype 19F (N=445,446)	89.2 (86 to 91.9)	99.8 (98.8 to 100)
7vPnC - Serotype 23F (N=444,445)	96.8 (94.8 to 98.3)	96.2 (94 to 97.8)
Additional - Serotype 1 (N=445,444)	1.8 (0.8 to 3.5)	99.5 (98.4 to 99.9)
Additional - Serotype 3 (N=443, 445)	3.2 (1.7 to 5.2)	99.3 (98 to 99.9)
Additional - Serotype 5 (N=445, 446)	23.6 (19.7 to 27.8)	99.6 (98.4 to 99.9)
Additional - Serotype 6A (N=446, 446)	59.9 (55.2 to 64.4)	98.2 (96.5 to 99.2)
Additional - Serotype 7F (N=445, 445)	4 (2.4 to 6.3)	99.8 (98.8 to 100)
Additional - Serotype 19A (N=446, 445)	74.4 (70.1 to 78.4)	99.6 (98.4 to 99.9)

Statistical analysis for 7vPnC - serotype 4.

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group. Percentage of responders was statistically significant between the groups if lower bound of 97.5 percent (%)confidence interval (CI) greater than (>) 0%.

Comparison groups

13vPnC Group 2 v 7vPnC Group 1

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Mean difference (final values)

Point estimate

0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

1.5

Notes
[2] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for 7vPnC -serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Mean difference (final values)

Point estimate

-2.9

Confidence interval

level

97.5%

sides

2-sided

lower limit

-6.5

upper limit

0.5

Notes
[3] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for 7vPnC -serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.3

upper limit

1.3

Notes
[4] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for 7vPnC - serotype 14.

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.9

upper limit

0.6

Notes
[5] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for 7vPnC - serotype 18C.

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.4

upper limit

1.4

Notes
[6] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Mean difference (final values)

Point estimate

10.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

7.5

upper limit

14.3

Notes
[7] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for 7vPnC - serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

-3.6

upper limit

2.2

Notes
[8] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was greater than -10%.

Statistical analysis for Additional serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

97.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

95.6

upper limit

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

96.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

93.6

upper limit

97.9

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

71.1

upper limit

80.4

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

38.3

Confidence interval

level

97.5%

sides

2-sided

lower limit

32.9

upper limit

43.8

Statistical analysis for Additional serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

25.1

Confidence interval

level

97.5%

sides

2-sided

lower limit

20.6

upper limit

Statistical analysis for Additional serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

95.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

93.1

upper limit

97.6

Primary: Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 3 vs 7vPnC Group 1

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End point title

Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 3 vs 7vPnC Group 1 ^[9]

End point description

The proportion of subjects achieving serotype-specific IgG concentrations ≥0.35 µg/mL 1 month after the infant series is presented for all common serotypes and 6 additional serotypes. For immunogenicity evaluation, 3 blood samples (approximately 5 mL) were collected during the course of the study. For subjects in Groups 1, blood samples were collected at the 6-, 12-, and 13-month visits. For Group 3 subjects, blood samples were collected at the 7-, 12-, and 13 month visits. In the below table 'N' represents the number of subjects with a determinate IgG antibody concentration to the given serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Primary

End point timeframe

1 month after the infant series (7 months of age)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	446	440
Units: Percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=444, 436)	99.8 (93.9 to 97.7)	100 (98.4 to 99.9)
7vPnC - Serotype 6B (N=441, 438)	96.1 (98.8 to 100)	94.7 (98.4 to 99.9)
7vPnC - Serotype 9V (N=446, 440)	99.8 (99.2 to 100)	99.5 (96.7 to 99.4)
7vPnC - Serotype 14 (N=446, 440)	100 (97.7 to 99.8)	99.5 (96.4 to 99.2)
7vPnC - Serotype 18C (N=446,440)	99.1 (86 to 91.9)	98.4 (93 to 97.2)
7vPnC - Serotype 19F (N=438,445)	89.2 (94.8 to 98.3)	98.2 (99.2 to 100)
7vPnC - Serotype 23F (N=444,438)	96.8 (0.8 to 3.5)	95.4 (95.3 to 98.6)
Additional - Serotype 1 (N=445, 440)	1.8 (1.7 to 5.2)	100 (97.7 to 99.8)
Additional - Serotype 3 (N=443, 439)	3.2 (19.7 to 27.8)	97.3 (96.1 to 99.1)
Additional - Serotype 5 (N=445, 439)	23.6 (55.2 to 64.4)	99.1 (99.2 to 100)
Additional - Serotype 6A (N=446, 439)	59.9 (98.8 to 100)	97.9 (98 to 99.9)
Additional - Serotype 7F (N=445, 439)	4 (2.4 to 6.3)	100 (99.2 to 100)
Additional - Serotype 19A (N=446, 439)	74.4 (70.1 to 78.4)	99.3 (92.2 to 96.6)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Mean difference (final values)

Point estimate

0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

1.5

Notes
[10] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

Mean difference (final values)

Point estimate

-1.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.7

upper limit

1.8

Notes
[11] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for 7vPnC -serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.7

upper limit

1.1

Notes
[12] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1.9

upper limit

0.7

Notes
[13] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

Parameter type

Mean difference (final values)

Point estimate

-0.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

-2.8

upper limit

1.2

Notes
[14] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

5.3

upper limit

12.9

Notes
[15] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for 7vPnC - serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

Parameter type

Mean difference (final values)

Point estimate

-1.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

-4.6

upper limit

1.6

Notes
[16] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the difference in proportion of responders (13vPnC – 7vPnC) was > -10%.

Statistical analysis for Additional - serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

98.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

96.2

upper limit

99.3

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

94.1

Confidence interval

level

97.5%

sides

2-sided

lower limit

upper limit

96.4

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

13vPnC Group 3 v 7vPnC Group 1

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

75.5

Confidence interval

level

97.5%

sides

2-sided

lower limit

70.6

upper limit

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

13vPnC Group 3 v 7vPnC Group 1

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

38.1

Confidence interval

level

97.5%

sides

2-sided

lower limit

32.7

upper limit

43.6

Statistical analysis for Additional- serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

93.3

upper limit

97.8

Statistical analysis for Additional - serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

24.9

Confidence interval

level

97.5%

sides

2-sided

lower limit

20.3

upper limit

29.8

Primary: Geometric Mean Concentration (GMC) for serotype-specific pneumococcal immunoglobulin G (IgG) antibody 1 month after the infant series, 13vPnC Group 2 vs 7vPnC Group 1

Top of page

End point title

Geometric Mean Concentration (GMC) for serotype-specific pneumococcal immunoglobulin G (IgG) antibody 1 month after the infant series, 13vPnC Group 2 vs 7vPnC Group 1 ^[17]

End point description

Antibody GMC for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC and corresponding 2-sided 95% CI were evaluated. Geometric means (GMs) were calculated using all subjects with available data for the specified blood draw. In the below table 'N' represents the number of subjects with a determinate antibody concentration for the specified serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Primary

End point timeframe

1 month after the infant series (6 months of age)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	446	446
Units: microgram per milliliter (mcg/mL)
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=444, 445)	15.36 (14.14 to 16.69)	11.96 (11.08 to 12.91)
7vPnC - Serotype 6B (N=441, 444)	2.88 (2.57 to 3.21)	2.64 (2.35 to 2.96)
7vPnC - Serotype 9V (N=446, 445)	6.76 (6.28 to 7.27)	5.25 (4.9 to 5.62)
7vPnC - Serotype 14 (N=446, 445)	17.79 (16.21 to 19.53)	16.36 (14.77 to 18.13)
7vPnC - Serotype 18C (N=446,444)	6.01 (5.54 to 6.53)	5.71 (5.23 to 6.23)
7vPnC - Serotype 19F (N=445,446)	5.7 (4.79 to 6.77)	7.4 (6.86 to 7.98)
7vPnC - Serotype 23F (N=444,445)	4.45 (4.03 to 4.91)	3.97 (3.57 to 4.4)
Additional - Serotype 1 (N=445,444)	0.01 (0.01 to 0.01)	7.02 (6.44 to 7.65)
Additional - Serotype 3 (N=443,445)	0.02 (0.02 to 0.02)	4.13 (3.83 to 4.47)
Additional - Serotype 5 (N=445, 446)	0.23 (0.21 to 0.25)	3.43 (3.18 to 3.7)
Additional - Serotype 6A (N=446, 446)	0.5 (0.46 to 0.55)	3.8 (3.5 to 4.13)
Additional - Serotype 7F (N=445, 445)	0.03 (0.03 to 0.03)	7.84 (7.29 to 8.42)
Additional - Serotype 19A (N=446, 445)	0.57 (0.53 to 0.62)	7.96 (7.28 to 8.7)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. GMCs were significantly higher in 13vPnC Group 2 than 7vPnC Group 1 if lower bound of 97.5% CI GMC ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

GMC ratio

Point estimate

0.78

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.68

upper limit

0.89

Notes
[18] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

Parameter type

GMC ratio

Point estimate

0.92

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.76

upper limit

1.1

Notes
[19] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

Parameter type

GMC ratio

Point estimate

0.78

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.69

upper limit

0.87

Notes
[20] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

GMC ratio

Point estimate

0.92

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.79

upper limit

1.08

Notes
[21] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

GMC ratio

Point estimate

0.95

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.83

upper limit

1.09

Notes
[22] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Parameter type

GMC ratio

Point estimate

1.3

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.05

upper limit

1.61

Notes
[23] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

Parameter type

GMC ratio

Point estimate

0.89

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.76

upper limit

1.05

Notes
[24] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for Additional - serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

823.89

Confidence interval

level

97.5%

sides

2-sided

lower limit

697.26

upper limit

973.52

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

240.05

Confidence interval

level

97.5%

sides

2-sided

lower limit

202.16

upper limit

285.05

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

14.93

Confidence interval

level

97.5%

sides

2-sided

lower limit

13.15

upper limit

16.95

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

7.54

Confidence interval

level

97.5%

sides

2-sided

lower limit

6.54

upper limit

8.69

Statistical analysis for Additional serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

256.65

Confidence interval

level

97.5%

sides

2-sided

lower limit

217.11

upper limit

303.38

Statistical analysis for Additional - serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

13.86

Confidence interval

level

97.5%

sides

2-sided

lower limit

12.13

upper limit

15.84

Primary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, Group 3 vs 7vPnC Group 1

Top of page

End point title

GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, Group 3 vs 7vPnC Group 1 ^[25]

End point description

Antibody GMC for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all subjects with available data for the specified blood draw. In the below table 'N' represents the number of subjects with a determinate antibody concentration for the specified serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required timeframe, received no prohibited vaccines and had no major protocol deviation.

End point type

Primary

End point timeframe

1 month after the infant series (7 months of age)

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	446	440
Units: mcg/mL
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=444,436)	15.36 (14.14 to 16.69)	9.71 (8.97 to 10.52)
7vPnC - Serotype 6B (N=441, 438)	2.88 (2.57 to 3.21)	3.21 (2.85 to 3.61)
7vPnC - Serotype 9V (N=446, 440)	6.76 (6.28 to 7.27)	4.27 (3.97 to 4.6)
7vPnC - Serotype 14 (N=446, 440)	17.79 (16.21 to 19.53)	17.11 (15.44 to 18.96)
7vPnC - Serotype 18C (N=446, 440)	6.01 (5.54 to 6.53)	5.76 (5.25 to 6.33)
7vPnC - Serotype 19F (N=445,438)	5.7 (4.79 to 6.77)	6.93 (6.26 to 7.66)
7vPnC - Serotype 23F (N=444, 438)	4.45 (4.03 to 4.91)	4.02 (3.58 to 4.51)
Additional - Serotype 1 (N=445, 440)	0.01 (0.01 to 0.01)	7.77 (7.16 to 8.45)
Additional - Serotype 3 (N=443, 439)	0.02 (0.02 to 0.02)	1.68 (1.56 to 1.82)
Additional - Serotype 5 (N=445, 439)	0.23 (0.21 to 0.25)	3.61 (3.33 to 3.9)
Additional - Serotype 6A (N=446, 439)	0.5 (0.46 to 0.55)	4.76 (4.34 to 5.23)
Additional - Serotype 7F (N=445, 439)	0.03 (0.03 to 0.03)	8.28 (7.7 to 8.91)
Additional - Serotype 19A (N=446, 439)	0.57 (0.53 to 0.62)	5.1 (4.68 to 5.57)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. GMCs were significantly higher in 13vPnC Group 3 than 7vPnC Group 1 if lower bound of 97.5% CI GMC ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

Parameter type

GMC ratio

Point estimate

0.63

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.55

upper limit

0.72

Notes
[26] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

Method

Parameter type

GMC ratio

Point estimate

1.12

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.93

upper limit

1.34

Notes
[27] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

Method

Parameter type

GMC ratio

Point estimate

0.63

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.56

upper limit

0.71

Notes
[28] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.82

upper limit

1.13

Notes
[29] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.83

upper limit

1.1

Notes
[30] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

Method

Parameter type

GMC ratio

Point estimate

1.22

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.97

upper limit

1.53

Notes
[31] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

Method

Parameter type

GMC ratio

Point estimate

0.9

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.76

upper limit

1.08

Notes
[32] - Noninferiority of 13vPnC in comparison with 7vPnC was assessed with respect to the 7 common serotypes (only). The noninferiority criterion was met for each serotype if the lower limit of the 97.5% CI for the GMC ratio (13vPnC / 7vPnC) was > 0.5.

Statistical analysis for Additional - serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

912.65

Confidence interval

level

97.5%

sides

2-sided

lower limit

773.95

upper limit

1076.22

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

97.77

Confidence interval

level

97.5%

sides

2-sided

lower limit

82.27

upper limit

116.19

Statistical analysis for Additional - serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

15.69

Confidence interval

level

97.5%

sides

2-sided

lower limit

13.79

upper limit

17.86

Statistical analysis for Additional - serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

9.45

Confidence interval

level

97.5%

sides

2-sided

lower limit

8.13

upper limit

10.97

Statistical analysis for Additional - serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

271.28

Confidence interval

level

97.5%

sides

2-sided

lower limit

229.23

upper limit

321.04

Statistical analysis for Additional - serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

8.89

Confidence interval

level

97.5%

sides

2-sided

lower limit

7.8

upper limit

10.14

Primary: Percentage of subjects reporting local reactions within 7 days after dose 1 in infant series

Top of page

End point title

Percentage of subjects reporting local reactions within 7 days after dose 1 in infant series ^[33]

End point description

Following local reactions were assessed: redness, swelling, and tenderness at the site of the pneumococcal conjugate injection. Details of local reactions were collected via e-diary for 7 days after each 13vPnC or 7vPnC vaccination. The below table included following for redness and swelling: Any, Mild (0.5-2.0 centimeters [cm]), Moderate (greater than [>] 2.0-7.0 cm), and Severe (>7.0 cm).For tenderness following are presented: Any, Present, and Significant (present and interfered with limb movement). N = number of subjects reporting yes for at least 1 day or no for all 7 days. Infant series safety population was used after dose 1. The safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

Within 7 days of dose 1 of infant series

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Number of subjects analysed	472 ^[34]	472 ^[35]	476 ^[36]	234 ^[37]
Units: Percentage of subjects
number (confidence interval 95%)
Redness - Any (N=470, 472, 472, 233)	4 (2.5 to 6.2)	3.2 (1.8 to 5.2)	5.7 (3.8 to 8.2)	3.4 (1.5 to 6.7)
Redness - Mild (N=470, 472, 472, 233)	4 (2.5 to 6.2)	3.2 (1.8 to 5.2)	5.5 (3.6 to 8)	3.4 (1.5 to 6.7)
Redness - Moderate (N=470, 472, 471, 233)	0.2 (0 to 1.2)	0 (0 to 0.8)	0.6 (0.1 to 1.9)	0 (0 to 1.6)
Redness - Severe (N=470, 472, 471, 233)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Swelling - Any (N=470, 472, 472, 233)	5.5 (3.6 to 8)	4 (2.4 to 6.2)	5.5 (3.6 to 8)	5.6 (3 to 9.4)
Swelling - Mild (N=470, 472, 472, 233)	4.9 (3.1 to 7.3)	3.4 (1.9 to 5.4)	5.1 (3.3 to 7.5)	5.2 (2.7 to 8.8)
Swelling - Moderate (N=470, 472, 471, 233)	1.1 (0.3 to 2.5)	0.6 (0.1 to 1.8)	1.1 (0.3 to 2.5)	0.9 (0.1 to 3.1)
Swelling - Severe (N=470, 472, 471, 233)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Tenderness - Any (N=470, 472, 472, 233)	4.3 (2.6 to 6.5)	3.2 (1.8 to 5.2)	7.6 (5.4 to 10.4)	5.2 (2.7 to 8.8)
Tenderness - Present (N=470, 472, 472, 233)	3.8 (2.3 to 6)	3 (1.6 to 4.9)	7.6 (5.4 to 10.4)	3.9 (1.8 to 7.2)
Tenderness - Significant (N=470, 472, 471, 233)	0.4 (0.1 to 1.5)	0.2 (0 to 1.2)	0 (0 to 0.8)	1.3 (0.3 to 3.7)

Notes
[34] - Analysed subjects includes the number of subjects who received dose 1 vaccination.
[35] - Analysed subjects includes the number of subjects who received dose 1 vaccination.
[36] - Analysed subjects includes the number of subjects who received dose 1 vaccination.
[37] - Analysed subjects includes the number of subjects who received dose 1 vaccination.

No statistical analyses for this end point

Primary: Percentage of subjects reporting local reactions within 7 days after dose 2 in infant series

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End point title

Percentage of subjects reporting local reactions within 7 days after dose 2 in infant series ^[38]

End point description

Following local reactions were assessed: redness, swelling, and tenderness at the site of the pneumococcal conjugate injection. Details of local reactions were collected via e-diary for 7 days after each 13vPnC or 7vPnC vaccination. The below table included following for redness and swelling: Any, Mild (0.5-2.0 cm), Moderate (>2.0-7.0 cm), and Severe (>7.0 cm). For tenderness following are presented: Any, Present, and Significant (present and interfered with limb movement). In the below table the section. N = number of subjects reporting yes for at least 1 day or no for all 7 days. Infant series safety population was used after dose 2. The safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

Within 7 days of dose 2 of infant series

Notes
[38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Number of subjects analysed	466 ^[39]	469 ^[40]	467 ^[41]	232 ^[42]
Units: percentage of subjects
number (confidence interval 95%)
Redness - Any (N=459, 462, 460, 232)	2.8 (1.5 to 4.8)	2.2 (1 to 3.9)	4.3 (2.7 to 6.6)	1.7 (0.5 to 4.4)
Redness - Mild (N=459, 462, 460, 232)	2.6 (1.4 to 4.5)	1.7 (0.8 to 3.4)	3.9 (2.3 to 6.1)	1.7 (0.5 to 4.4)
Redness - Moderate (N=459, 462, 460, 232)	0.4 (0.1 to 1.6)	0.6 (0.1 to 1.9)	0.7 (0.1 to 1.9)	1.7 (0.5 to 4.4)
Redness - Severe (N=459, 462, 459, 232)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Swelling - Any (N=459, 462, 459, 232)	3.5 (2 to 5.6)	2.4 (1.2 to 4.2)	4.1 (2.5 to 6.4)	1.7 (0.5 to 4.4)
Swelling - Mild (N=459, 462, 459, 232)	3.3 (1.8 to 5.3)	2.2 (1 to 3.9)	3.7 (2.2 to 5.9)	1.7 (0.5 to 4.4)
Swelling - Moderate (N=459, 462, 459, 232)	0.7 (0.1 to 1.9)	0.4 (0.1 to 1.6)	0.4 (0.1 to 1.6)	0.4 (0 to 2.4)
Swelling - Severe (N=459, 462, 459, 232)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Tenderness - Any (N=459, 462, 460, 232)	2.8 (1.5 to 4.8)	2.4 (1.2 to 4.2)	6.1 (4.1 to 8.7)	2.6 (1 to 5.5)
Tenderness - Present (N=459, 462, 460, 232)	2.6 (1.4 to 4.5)	1.9 (0.9 to 3.7)	6.1 (4.1 to 8.7)	2.6 (1 to 5.5)
Tenderness - Significant (N=459, 462, 459, 232)	0.2 (0 to 1.2)	0.4 (0.1 to 1.6)	0 (0 to 0.8)	0 (0 to 1.6)

Notes
[39] - Analysed subjects includes the number of subjects who received dose 2 vaccination.
[40] - Analysed subjects includes the number of subjects who received dose 2 vaccination.
[41] - Analysed subjects includes the number of subjects who received dose 2 vaccination.
[42] - Analysed subjects includes the number of subjects who received dose 2 vaccination.

No statistical analyses for this end point

Primary: Percentage of subjects reporting local reactions within 7 days after dose 3 in infant series

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End point title

Percentage of subjects reporting local reactions within 7 days after dose 3 in infant series ^[43] ^[44]

End point description

Following local reactions were assessed: redness, swelling, and tenderness at the site of the pneumococcal conjugate injection. Details of local reactions were collected via e-diary for 7 days after each 13vPnC or 7vPnC vaccination. The below table included following for redness and swelling: Any, Mild (0.5-2.0 cm), Moderate (>2.0-7.0 cm), and Severe (>7.0 cm).For tenderness following are presented: Any, Present, and Significant (present and interfered with limb movement). In the below table, N = number of subjects reporting yes for at least 1 day or no for all 7 days. Infant series safety population was used after dose 3. The safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

Within 7 days of dose 3 of infant series

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: Only descriptive data was planned to be reported for this endpoint.
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3
Number of subjects analysed	463	467	460
Units: percentage of subjects
number (confidence interval 95%)
Redness -Any (N=463, 467, 460)	1.9 (0.9 to 3.7)	2.1 (1 to 3.9)	1.7 (0.8 to 3.4)
Redness- Mild (N=463, 467, 460)	1.7 (0.7 to 3.4)	2.1 (1 to 3.9)	1.1 (0.4 to 2.5)
Redness- Moderate (N=463, 467, 460)	0.2 (0 to 1.2)	0.2 (0 to 1.2)	0.9 (0.2 to 2.2)
Redness- Severe (N= 463, 467, 460)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)
Swelling- Any (463, 467, 460)	1.9 (0.9 to 3.7)	1.9 (0.9 to 3.6)	2.4 (1.2 to 4.2)
Swelling -Mild (N=463, 467, 460)	1.9 (0.9 to 3.7)	1.9 (0.9 to 3.6)	2.2 (1 to 4)
Swelling -Moderate (N=463, 467, 460)	0 (0 to 0.8)	0.2 (0 to 1.2)	0.7 (0.1 to 1.9)
Swelling -Severe (N= 463, 467, 460)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)
Tenderness-Any (463, 467, 460)	5 (3.2 to 7.4)	3.4 (2 to 5.5)	3.5 (2 to 5.6)
Tenderness- Present (N=463, 467, 460)	4.3 (2.7 to 6.6)	3.2 (1.8 to 5.2)	3.3 (1.8 to 5.3)
Tenderness-Significant (N=463, 467, 460)	0.6 (0.1 to 1.9)	0.2 (0 to 1.2)	0.2 (0 to 1.2)

No statistical analyses for this end point

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 1 in infant series

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End point title

Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 1 in infant series ^[45]

End point description

Following systemic events were assessed: decreased appetite, irritability, increased sleep, decreased sleep, fever, and use of antipyretic medication to treat or prevent symptoms. N = number of subjects reporting yes for at least 1 day or no for all 7 days. Infant series safety population was used after dose 1. The safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

Within 7 days after dose 1 of infant series

Notes
[45] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Number of subjects analysed	472 ^[46]	472 ^[47]	476 ^[48]	234 ^[49]
Units: percentage of subjects
number (confidence interval 95%)
Temperature ≥38 degree (°)C (N=470, 472, 472, 233)	0.6 (0.1 to 1.9)	1.1 (0.3 to 2.5)	1.7 (0.7 to 3.3)	1.3 (0.3 to 3.7)
Temperature ≥38°C but ≤39°C (N=470, 472, 472, 233)	0.6 (0.1 to 1.9)	1.1 (0.3 to 2.5)	1.7 (0.7 to 3.3)	1.3 (0.3 to 3.7)
Temperature >39°C but ≤40°C (N=470, 472, 471, 233)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Temperature >40°C (N=470, 472, 471, 233)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Decreased appetite (N=470, 472, 471, 233)	4.3 (2.6 to 6.5)	1.9 (0.9 to 3.6)	4.7 (3 to 7)	1.7 (0.5 to 4.3)
Irritability (N=470, 472, 472, 233)	4.7 (3 to 7)	3.4 (1.9 to 5.4)	12.3 (9.5 to 15.6)	4.3 (2.1 to 7.8)
Increased sleep (N=470, 472, 471, 233)	2.6 (1.3 to 4.4)	0.6 (0.1 to 1.8)	7.4 (5.2 to 10.2)	0.9 (0.1 to 3.1)
Decreased sleep (N=470, 472, 471, 233)	2.8 (1.5 to 4.7)	1.9 (0.9 to 3.6)	5.7 (3.8 to 8.2)	2.6 (1 to 5.5)
Antipyretic medication use (N=470, 472, 473, 233)	1.7 (0.7 to 3.3)	1.5 (0.6 to 3)	2.7 (1.5 to 4.7)	3 (1.2 to 6.1)

Notes
[46] - Analysed subjects includes the number of subjects who received dose 1 vaccination.
[47] - Analysed subjects includes the number of subjects who received dose 1 vaccination.
[48] - Analysed subjects includes the number of subjects who received dose 1 vaccination.
[49] - Analysed subjects includes the number of subjects who received dose 1 vaccination.

No statistical analyses for this end point

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 2 in infant series

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End point title

Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 2 in infant series ^[50]

End point description

Following systemic events were assessed: decreased appetite, irritability, increased sleep, decreased sleep, fever, and use of antipyretic medication to treat or prevent symptoms. N = number of subjects reporting yes for at least 1 day or no for all 7 days.Infant series safety population was used after dose 2. The safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

7 days after dose 2 of infant series

Notes
[50] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Number of subjects analysed	466 ^[51]	469 ^[52]	467 ^[53]	232 ^[54]
Units: Percentage of subjects
number (confidence interval 95%)
Temperature ≥38°C (N=459, 462, 459, 232)	0.9 (0.2 to 2.2)	1.5 (0.6 to 3.1)	1.7 (0.8 to 3.4)	1.3 (0.3 to 3.7)
Temperature ≥38°C but ≤39°C (N=459, 462, 459, 232)	0.9 (3.6 to 7.9)	1.5 (0.6 to 3.1)	1.7 (0.8 to 3.4)	1.3 (0.3 to 3.7)
Temperature >39°C but ≤40°C (N=459, 462, 459, 232)	0 (0.1 to 1.9)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 1.6)
Temperature >40°C (N=459, 462, 459, 232)	0 (0.8 to 3.4)	0 (1.2 to 4.2)	0 (0 to 0.8)	0 (0 to 1.6)
Decreased appetite (N=459, 462, 459, 232)	2.6 (0.6 to 3.1)	1.9 (0 to 0.8)	2 (0.9 to 3.7)	0.4 (0 to 2.4)
Irritability (N=459, 462, 460, 232)	5.4 (0.2 to 2.2)	3.7 (0.9 to 3.7)	3.3 (1.8 to 5.3)	0.9 (0.1 to 3.1)
Increased sleep (N=459, 462, 459, 232)	0.7 (0 to 0.8)	0 (2.2 to 5.8)	0.2 (0 to 1.2)	0.4 (0 to 2.4)
Decreased sleep (N=459, 462, 459, 232)	1.7 (0 to 0.8)	1.7 (0 to 0.8)	1.3 (0.5 to 2.8)	0 (0 to 1.6)
Antipyretic medication use (N=459, 462, 459, 232)	1.5 (1.4 to 4.5)	2.4 (0.8 to 3.4)	2 (0.9 to 3.7)	0.9 (0.1 to 3.1)

Notes
[51] - Analysed subjects includes the number of subjects who received dose 2 vaccination.
[52] - Analysed subjects includes the number of subjects who received dose 2 vaccination.
[53] - Analysed subjects includes the number of subjects who received dose 2 vaccination.
[54] - Analysed subjects includes the number of subjects who received dose 2 vaccination.

No statistical analyses for this end point

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 3 in infant series

Top of page

End point title

Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 3 in infant series ^[55] ^[56]

End point description

Following systemic events were assessed: decreased appetite, irritability, increased sleep, decreased sleep, fever, and use of antipyretic medication to treat or prevent symptoms. N = number of subjects reporting yes for at least 1 day or no for all 7 days. Infant series safety population was used after dose 3. The safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

7 days after dose 3 of infant series

Notes
[55] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.
[56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3
Number of subjects analysed	462 ^[57]	467 ^[58]	464 ^[59]
Units: Percentage of subjects
number (confidence interval 95%)
Temperature ≥38°C (N=463, 467, 460)	1.7 (0.7 to 3.4)	2.1 (1 to 3.9)	1.7 (0.8 to 3.4)
Temperature ≥38°C but ≤39°C (N=463, 467, 460)	1.5 (0.6 to 3.1)	1.9 (0.9 to 3.6)	1.7 (0.8 to 3.4)
Temperature >39°C but ≤40°C (N=463, 467, 460)	0.2 (0 to 1.2)	0.2 (0 to 1.2)	0.2 (0 to 1.2)
Temperature >40°C (N=463, 467, 460)	0 (0 to 0.8)	0 (0 to 0.8)	0 (0 to 0.8)
Decreased appetite (N=463, 467, 460)	2.4 (1.2 to 4.2)	1.3 (0.5 to 2.8)	2.4 (1.2 to 4.2)
Irritability (N=463, 467, 460)	2.4 (1.2 to 4.2)	2.1 (1 to 3.9)	4.3 (2.7 to 6.6)
Increased sleep (N=463, 467, 460)	0.6 (0.1 to 1.9)	0.4 (0.1 to 1.5)	0.4 (0.1 to 1.6)
Decreased sleep (N=463, 467, 460)	0.2 (0 to 1.2)	0.9 (0.2 to 2.2)	1.3 (0.5 to 2.8)
Antipyretic medication use (N=463, 467, 460)	2.2 (1 to 3.9)	1.7 (0.7 to 3.3)	3 (1.7 to 5.1)

Notes
[57] - Analysed subjects includes the number of subjects who received dose 3 vaccination.
[58] - Analysed subjects includes the number of subjects who received dose 3 vaccination.
[59] - Analysed subjects includes the number of subjects who received dose 3 vaccination.

No statistical analyses for this end point

Primary: Percentage of subjects reporting local reactions within 7 days after toddler dose

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End point title

Percentage of subjects reporting local reactions within 7 days after toddler dose ^[60]

End point description

Following local reactions were assessed: redness, swelling, and tenderness at the site of the pneumococcal conjugate injection. Details of local reactions were collected via e-diary for 7 days after each 13vPnC or 7vPnC vaccination. The below table included following for redness and swelling: Any, Mild (0.5-2.0 cm), Moderate (>2.0-7.0 cm), and Severe (>7.0 cm).For tenderness following are presented: Any, Present, and Significant (present and interfered with limb movement).N = number of subjects reporting yes for at least 1 day or no for all 7 days. The safety analysis set after toddler dose was used. Safety analysis set included all subjects who received at least 1 dose of investigational product.

End point type

Primary

End point timeframe

Within 7 days of toddler dose vaccination

Notes
[60] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Number of subjects analysed	436 ^[61]	447 ^[62]	448 ^[63]	225 ^[64]
Units: percentage of subjects
number (confidence interval 95%)
Redness - Any (N=432, 447, 446, 225)	2.1 (1 to 3.9)	3.4 (1.9 to 5.5)	3.6 (2.1 to 5.8)	1.8 (0.5 to 4.5)
Redness - Mild (N=432, 447, 446, 225)	1.4 (0.5 to 3)	2.5 (1.2 to 4.4)	2.5 (1.2 to 4.4)	0.4 (0 to 2.5)
Redness - Moderate (N=432, 447, 446, 225)	1.4 (0.5 to 3)	1.6 (0.6 to 3.2)	1.3 (0.5 to 2.9)	1.3 (0.3 to 3.8)
Redness - Severe (N=432, 447, 446, 225)	0 (0 to 0.9)	0 (0 to 0.8)	0 (0 to 0.8)	0.4 (0 to 2.5)
Swelling - Any (N=432, 447, 446, 225)	3.5 (2 to 5.7)	3.6 (2.1 to 5.7)	3.6 (2.1 to 5.8)	3.1 (1.3 to 6.3)
Swelling - Mild (N=432, 447, 446, 225)	2.3 (1.1 to 4.2)	2.7 (1.4 to 4.6)	2.7 (1.4 to 4.7)	1.8 (0.5 to 4.5)
Swelling - Moderate (N=432, 447, 446, 225)	1.6 (0.7 to 3.3)	1.3 (0.5 to 2.9)	1.3 (0.5 to 2.9)	1.8 (0.5 to 4.5)
Swelling - Severe (N=432, 447, 446, 225)	0 (0 to 0.9)	0 (0 to 0.8)	0 (0 to 0.8)	0.4 (0 to 2.5)
Tenderness - Any (N=432, 447, 446, 225)	6.5 (4.3 to 9.2)	4.9 (3.1 to 7.4)	5.4 (3.5 to 7.9)	5.3 (2.8 to 9.1)
Tenderness - Present (N=432, 447, 446, 225)	6.5 (4.3 to 9.2)	4.5 (2.8 to 6.8)	4.7 (2.9 to 7.1)	5.3 (2.8 to 9.1)
Tenderness - Significant (N=432, 447, 446, 225)	0 (0 to 0.9)	0.4 (0.1 to 1.6)	0.7 (0.1 to 2)	0 (0 to 1.6)

Notes
[61] - Analysed subjects includes the number of subjects who received toddler dose.
[62] - Analysed subjects includes the number of subjects who received toddler dose.
[63] - Analysed subjects includes the number of subjects who received toddler dose.
[64] - Analysed subjects includes the number of subjects who received toddler dose.

No statistical analyses for this end point

Primary: Percentage of Subjects reporting systemic events and antipyretic medication use within 7 days after toddler dose

Top of page

End point title

Percentage of Subjects reporting systemic events and antipyretic medication use within 7 days after toddler dose ^[65]

End point description

End point type

Primary

End point timeframe

within 7 days of toddler dose vaccination

Notes
[65] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive data was planned to be reported for this endpoint.

End point values	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Number of subjects analysed	436 ^[66]	447 ^[67]	448 ^[68]	225 ^[69]
Units: Percentage of subjects
number (confidence interval 95%)
Temperature ≥38°C (N=432, 447, 446, 225)	3.2 (0.8 to 5.4)	6.7 (4.6 to 9.4)	6.7 (4.6 to 9.5)	6.2 (3.4 to 10.2)
Temperature ≥38°C but ≤39°C (N=432, 447, 446, 225)	3.2 (1.8 to 5.4)	6.5 (4.4 to 9.2)	6.3 (4.2 to 8.9)	6.2 (3.4 to 10.2)
Temperature >39°C but ≤40°C (N=432, 447, 446, 225)	0.2 (0 to 1.3)	0.9 (0.2 to 2.3)	0.4 (0.1 to 1.6)	0 (0 to 1.6)
Temperature >40°C (N=432, 447, 446, 225)	0 (0 to 0.9)	0.2 (0 to 1.2)	0 (0 to 0.8)	0 (0 to 1.6)
Decreased appetite (N=433, 447, 446, 225)	3.5 (2 to 5.6)	2.5 (1.2 to 4.4)	2.5 (1.2 to 4.4)	2.2 (0.7 to 5.1)
Irritability (N=432, 447, 446, 225)	4.4 (2.7 to 6.8)	3.4 (1.9 to 5.5)	3.6 (2.1 to 5.8)	3.1 (1.3 to 6.3)
Increased sleep (N=432, 447, 446, 225)	0.7 (0.1 to 2)	0 (0 to 0.8)	0 (0 to 0.8)	0.4 (0 to 2.5)
Decreased sleep (N=432, 447, 446, 225)	1.6 (0.7 to 3.3)	2.2 (1.1 to 4.1)	1.6 (0.6 to 3.2)	0.9 (0.1 to 3.2)
Antipyretic medication use (N=432, 447, 446, 225)	5.3 (3.4 to 7.9)	5.4 (3.5 to 7.9)	5.4 (3.5 to 7.9)	4.4 (2.2 to 8)

Notes
[66] - Analysed subjects includes the number of subjects who received toddler dose.
[67] - Analysed subjects includes the number of subjects who received toddler dose.
[68] - Analysed subjects includes the number of subjects who received toddler dose.
[69] - Analysed subjects includes the number of subjects who received toddler dose.

No statistical analyses for this end point

Secondary: Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1

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End point title

Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1 ^[70]

End point description

The proportion of subjects achieving serotype-specific IgG concentrations ≥0.35 µg/mL 1 month after the infant series is presented for all common serotypes and 6 additional serotypes. For immunogenicity evaluation, 3 blood samples (approximately 5 mL) were collected during the course of the study. For subjects in Groups 1, blood samples were collected at the 6-, 12-, and 13-month visits. For Group 4 subjects, blood samples were collected at the 6-, 12-, and 13 month visits. In the below table 'N' represents the number of subjects with a determinate IgG antibody concentration to the given serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the infant series (6 months of age)

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	446	224
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=444,224)	99.8 (98.8 to 100)	99.6 (97.5 to 100)
7vPnC - Serotype 6B (N=441,224)	96.1 (93.9 to 97.7)	70.1 (63.6 to 76)
7vPnC - Serotype 9V (N= 446, 224)	99.8 (98.8 to 100)	98.2 (95.5 to 99.5)
7vPnC - Serotype 14 (N= 446,223)	100 (99.2 to 100)	99.1 (96.8 to 99.9)
7vPnC - Serotype 18C (N= 446, 223)	99.1 (97.7 to 99.8)	95.5 (91.9 to 97.8)
7vPnC - Serotype 19F (N= 445, 224)	89.2 (86 to 91.9)	98.7 (96.1 to 99.7)
7vPnC - Serotype 23F (N= 444, 224)	96.8 (94.8 to 98.3)	90.6 (86 to 94.1)
Additional - Serotype 1 (N= 445,224)	1.8 (0.8 to 3.5)	100 (98.4 to 100)
Additional - Serotype 3 (N= 443, 224)	3.2 (1.7 to 5.2)	99.6 (97.5 to 100)
Additional - Serotype 5 (N= 445, 224)	23.6 (19.7 to 27.8)	98.2 (95.5 to 99.5)
Additional - Serotype 6A (N=446, 223)	59.9 (55.2 to 64.4)	97.3 (94.2 to 99)
Additional - Serotype 7F (N=445, 224)	4 (2.4 to 6.3)	100 (98.4 to 100)
Additional - Serotype 19A (N= 446, 224)	74.4 (70.1 to 78.4)	98.4 (96.1 to 99.7)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

-26.1

Confidence interval

level

95%

sides

2-sided

lower limit

-32.6

upper limit

-19.9

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1.6

Confidence interval

level

95%

sides

2-sided

lower limit

-4.1

upper limit

-0.1

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

0.1

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-3.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

-0.7

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

9.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

5.9

upper limit

12.9

Statistical analysis for 7vPnC - serotype 23F

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-10.9

upper limit

-2.2

Statistical analysis for Additional - serotype 1

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

98.2

Confidence interval

level

90%

sides

2-sided

lower limit

96.5

upper limit

99.3

Statistical analysis for Additional - serotype 3

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

96.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

93.9

upper limit

97.9

Statistical analysis for Additional - serotype 5

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

74.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

upper limit

78.7

Statistical analysis for Additional - serotype 7F

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

93.7

upper limit

97.6

Statistical analysis for Additional - serotype 6A

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

37.4

Confidence interval

level

95%

sides

2-sided

lower limit

32.3

upper limit

42.5

Statistical analysis for Additional - serotype 19A

Statistical analysis description

Difference in proportions, 13vPnC-7vPnC reference, expressed as percentage. The reference value is the corresponding proportion in 7vPnC group.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

24.2

Confidence interval

level

95%

sides

2-sided

lower limit

19.9

upper limit

28.7

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1

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End point title

GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1 ^[71]

End point description

Antibody GMC for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC and corresponding 2-sided 95% CI were evaluated. GMs were calculated using all subjects with available data for the specified blood draw. In the below table 'N' represents the number of subjects with a determinate antibody concentration for the specified serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the infant series (6 months of age)

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	446	224
Units: mcg/mL
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N= 444,224)	15.36 (2.57 to 13.21)	8.68 (7.62 to 9.88)
7vPnC - Serotype 6B (N= 441,224)	2.88 (6.28 to 7.27)	0.74 (0.62 to 0.89)
7vPnC - Serotype 9V (N= 446,224)	6.76 (16.21 to 19.53)	4.42 (3.88 to 5.04)
7vPnC - Serotype 14 (N= 446,223)	17.79 (14.14 to 16.69)	10.75 (8.99 to 12.87)
7vPnC - Serotype 18C (N= 446,223)	6.01 (5.54 to 6.53)	4.17 (3.6 to 4.84)
7vPnC - Serotype 19F (N= 445, 224)	5.7 (4.79 to 6.77)	10.64 (9 to 12.59)
7vPnC - Serotype 23F (N=444, 224)	4.45 (4.03 to 4.91)	2.29 (1.9 to 2.77)
Additional - Serotype 1 (N= 445,224)	0.01 (0.01 to 0.01)	6.98 (6.2 to 7.85)
Additional - Serotype 3 (N= 443, 224)	0.02 (0.02 to 0.02)	2.59 (2.32 to 2.9)
Additional - Serotype 5 (N= 445, 224)	0.23 (0.21 to 0.25)	3.19 (2.82 to 3.61)
Additional - Serotype 6A (N= 446,223)	0.5 (0.46 to 0.55)	4.18 (3.62 to 4.83)
Additional - Serotype 7F (N= 445,224)	0.03 (0.03 to 0.03)	8.12 (7.26 to 9.07)
Additional - Serotype 19A (N=446, 224)	0.57 (0.53 to 0.62)	6.41 (5.44 to 7.54)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

0.66

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

0.32

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

0.75

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.6

Confidence interval

level

97.5%

sides

2-sided

lower limit

0.5

upper limit

0.73

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.59

upper limit

0.81

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.87

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.42

upper limit

2.45

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

0.63

Statistical analysis for Additional - serotype 1

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

818.84

Confidence interval

level

95%

sides

2-sided

lower limit

680.02

upper limit

985.99

Statistical analysis for Additional - serotype 3

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

150.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

123.61

upper limit

183.73

Statistical analysis for Additional serotype 5

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

13.89

Confidence interval

level

97.5%

sides

2-sided

lower limit

12.03

upper limit

16.03

Statistical analysis for Additional serotype 6A

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

8.29

Confidence interval

level

97.5%

sides

2-sided

lower limit

7.02

upper limit

9.78

Statistical analysis for Additional- serotype 7F

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

265.93

Confidence interval

level

95%

sides

2-sided

lower limit

218.6

upper limit

323.51

Statistical analysis for Additional - serotype 19A

Statistical analysis description

CI for the ratio are back transformations of a CI based on the Student t distribution for the mean difference of the logarithms of the measures (13vPnC-7vPnC reference).

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

11.16

Confidence interval

level

95%

sides

2-sided

lower limit

9.55

upper limit

13.06

Secondary: Percentage of Subjects achieving a pneumococcal Opsonophagocytic Activity (OPA) antibody titer ≥ Lower Limit of Quantitation (LLOQ) in infant series, 13vPnC Group 2 vs 7vPnC Group 1

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End point title

Percentage of Subjects achieving a pneumococcal Opsonophagocytic Activity (OPA) antibody titer ≥ Lower Limit of Quantitation (LLOQ) in infant series, 13vPnC Group 2 vs 7vPnC Group 1 ^[72]

End point description

A randomly selected subset was analyzed for serum OPA elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1 and 2, blood samples (approximately 5 mL) were collected at the 6-, 12-, and 13-month visits. In the below table 'N' indicates the number of subjects with a determinate postinfant series OPA antibody titer to the given serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the infant series (6 Months of age)

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	446	446
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=112, 111)	100 (21.2 to 39.2)	100 (96.7 to 100)
7vPnC - Serotype 6B (N=114, 111)	97.4 (96.8 to 100)	99.1 (96.7 to 100)
7vPnC - Serotype 9V (N=110, 110)	97.3 (92.2 to 99.4)	97.3 (96.8 to 100)
7vPnC - Serotype 14 (N=110, 111)	100 (92.2 to 99.4)	100 (93.6 to 99.8)
7vPnC - Serotype 18C (N=111, 111)	100 (96.7 to 100)	100 (96.7 to 100)
7vPnC - Serotype 19F (N=107, 110)	97.2 (96.7 to 100)	97.2 (95.1 to 100)
7vPnC - Serotype 23F (N=110, 111)	97.3 (92.2 to 99.4)	97.3 (92.2 to 99.4)
Additional - Serotype 1 (N=112, 111)	0 (92.2 to 99.4)	95.5 (96.7 to 100)
Additional - Serotype 3 (N=115, 115)	5.2 (0 to 3.2)	100 (96.7 to 100)
Additional - Serotype 5 (N=113, 112)	0.9 (1.9 to 11)	98.2 (92.2 to 99.4)
Additional - Serotype 6A (N=105, 110)	83.8 (0 to 4.8)	100 (92.2 to 99.4)
Additional - Serotype 7F (N=102, 113)	6.9 (75.3 to 90.3)	100 (89.8 to 98.5)
Additional - Serotype 19A (N=108, 110)	29.6 (2.8 to 13.6)	98.2 (96.8 to 100)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

6.6

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

5.3

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

3.4

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

3.3

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

7.1

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

6.9

Statistical analysis for Additional - serotype 1

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

13vPnC Group 2 v 7vPnC Group 1

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

95.5

Confidence interval

level

95%

sides

2-sided

lower limit

89.8

upper limit

98.5

Statistical analysis for Additional serotype 3

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

94.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

98.1

Statistical analysis for Additional serotype 5

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

97.3

Confidence interval

level

95%

sides

2-sided

lower limit

92.3

upper limit

99.4

Statistical analysis for Additional serotype 6A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

9.7

upper limit

24.7

Statistical analysis for Additional- serotype 7F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

93.1

Confidence interval

level

95%

sides

2-sided

lower limit

86.4

upper limit

97.2

Statistical analysis for Additional - serotype 19A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

68.6

Confidence interval

level

95%

sides

2-sided

lower limit

58.8

upper limit

77.1

Secondary: Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 3 vs 7vPnC Group 1

Top of page

End point title

Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 3 vs 7vPnC Group 1 ^[73]

End point description

A randomly selected subset was analyzed for serum OPA elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1, blood samples were collected at the 6-, 12-, and 13-month visits. For Group 3 subjects, blood samples were collected at the 7-, 12-, and 13 month visits. In the below table 'N' indicates the number of subjects with a determinate postinfant series OPA antibody titer to the given serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the infant series (7 months of age)

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	446	440
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=112, 100)	100 (96.8 to 100)	100 (96.4 to 100)
7vPnC - Serotype 6B (N=114, 101)	97.4 (92.5 to 99.5)	98 (93 to 99.8)
7vPnC - Serotype 9V (N=110, 99)	97.3 (92.2 to 99.4)	97 (91.4 to 99.4)
7vPnC - Serotype 14 (N=110, 96)	100 (96.7 to 100)	100 (96.2 to 100)
7vPnC - Serotype 18C (N=111,98)	100 (96.7 to 100)	100 (96.3 to 100)
7vPnC - Serotype 19F (N=107, 97)	97.2 (92 to 99.4)	99 (94.4 to 100)
7vPnC - Serotype 23F (N=110,98)	97.3 (92.2 to 99.4)	96.9 (91.3 to 99.4)
Additional - Serotype 1 (N=112, 98)	0 (0 to 3.2)	96.9 (91.3 to 99.4)
Additional - Serotype 3 (N=115, 102)	5.2 (1.9 to 11)	100 (96.4 to 100)
Additional - Serotype 5 (N=113, 101)	0.9 (0 to 4.8)	95 (88.8 to 98.4)
Additional - Serotype 6A (N=105,97)	83.8 (75.3 to 90.3)	99 (94.4 to 100)
Additional - Serotype 7F (N=102, 100)	6.9 (2.8 to 13.6)	100 (96.4 to 100)
Additional - Serotype 19A (N=108,98)	29.6 (21.2 to 39.2)	98 (92.8 to 99.8)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

3.3

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

5.8

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.1

upper limit

5.1

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

3.4

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

3.4

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

7.1

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6.2

upper limit

5.1

Statistical analysis for Additional - serotype 1

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

96.9

Confidence interval

level

95%

sides

2-sided

lower limit

91.3

upper limit

99.4

Statistical analysis for Additional serotype 3

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

94.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

98.1

Statistical analysis for Additional serotype 5

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

94.2

Confidence interval

level

95%

sides

2-sided

lower limit

87.7

upper limit

97.8

Statistical analysis for Additional serotype 6A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

15.2

Confidence interval

level

95%

sides

2-sided

lower limit

7.4

upper limit

23.6

Statistical analysis for Additional- serotype 7F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

93.1

Confidence interval

level

95%

sides

2-sided

lower limit

86.4

upper limit

97.2

Statistical analysis for Additional - serotype 19A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

68.3

Confidence interval

level

95%

sides

2-sided

lower limit

58.5

upper limit

77.1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 4 vs 7vPnC Group 1

Top of page

End point title

Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 4 vs 7vPnC Group 1 ^[74]

End point description

A randomly selected subset was analyzed for serum OPA elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1, blood samples were collected at the 6-, 12-, and 13-month visits. For Group 4 subjects, blood samples were collected at the 6-, 12-, and 13 month visits. In the below table 'N' indicates the number of subjects with a determinate postinfant series OPA antibody titer to the given serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the infant series (7 months of age)

Notes
[74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	446	224
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=112, 101)	100 (96.8 to 100)	99 (94.6 to 100)
7vPnC - Serotype 6B (N=114, 99)	97.4 (92.5 to 99.5)	79.8 (70.5 to 87.2)
7vPnC - Serotype 9V (N=110,99)	97.3 (92.2 to 99.4)	90.9 (83.4 to 95.8)
7vPnC - Serotype 14 (N=110, 101)	100 (96.7 to 100)	100 (96.4 to 100)
7vPnC - Serotype 18C (N=111,103)	100 (96.7 to 100)	99 (94.7 to 100)
7vPnC - Serotype 19F (N=107,98)	97.2 (92 to 99.4)	99 (94.4 to 100)
7vPnC - Serotype 23F (N=110,102)	97.3 (92.2 to 99.4)	98 (93.1 to 99.8)
Additional - Serotype 1 (N=112, 102)	0 (0 to 3.2)	95.1 (88.9 to 98.4)
Additional - Serotype 3 (N=115, 107)	5.2 (1.9 to 11)	100 (96.6 to 100)
Additional - Serotype 5 (N=113, 104)	0.9 (0 to 4.8)	98.1 (93.2 to 99.8)
Additional - Serotype 6A (N=105, 102)	83.8 (75.3 to 90.3)	100 (96.4 to 100)
Additional - Serotype 7F (N=102, 104)	6.9 (2.8 to 13.6)	100 (96.4 to 100)
Additional - Serotype 19A (N=108, 102)	29.6 (21.2 to 39.2)	95.1 (88.9 to 98.4)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

2.3

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-6.4

Confidence interval

level

95%

sides

2-sided

lower limit

-14

upper limit

0.1

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-17.6

Confidence interval

level

95%

sides

2-sided

lower limit

-26.9

upper limit

-8.7

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

3.3

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.3

upper limit

2.4

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

7.1

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

6.1

Statistical analysis for Additional - serotype 1

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

13vPnC Group 4 v 7vPnC Group 1

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

95.1

Confidence interval

level

95%

sides

2-sided

lower limit

88.9

upper limit

98.4

Statistical analysis for Additional serotype 3

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

94.8

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

98.1

Statistical analysis for Additional serotype 6A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

16.2

Confidence interval

level

95%

sides

2-sided

lower limit

9.7

upper limit

24.7

Statistical analysis for Additional serotype 5

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

97.2

Confidence interval

level

95%

sides

2-sided

lower limit

92.1

upper limit

99.4

Statistical analysis for Additional- serotype 7F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

93.1

Confidence interval

level

95%

sides

2-sided

lower limit

86.4

upper limit

97.2

Statistical analysis for Additional - serotype 19A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

65.5

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

74.7

Secondary: Serotype-specific OPA Geometric Mean Titer (GMT) 1 month after the infant series 13vPnC Group 2 vs 7vPnC Group 1

Top of page

End point title

Serotype-specific OPA Geometric Mean Titer (GMT) 1 month after the infant series 13vPnC Group 2 vs 7vPnC Group 1 ^[75]

End point description

A randomly selected subset was analyzed for serum OPA GMT elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1 and 2, blood samples (approximately 5 mL) were collected at the 6-, 12-, and 13-month visits. In the below table 'N' represents the number of subjects with a determinate antibody titer for the specified serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the infant series (6 months of age)

Notes
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	446	446
Units: GMT
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=112, 111)	4650 (3890.2 to 7011.5)	4266 (3499.9 to 5198.8)
7vPnC - Serotype 6B (N=114, 111)	3725 (3804.6 to 5682.5)	3471 (2736 to 4402.5)
7vPnC - Serotype 9V (N=110, 110)	2727 (2834.3 to 4894.7)	2502 (1914 to 3270.1)
7vPnC - Serotype 14 (N=110, 111)	4301 (2097.7 to 3544.5)	3391 (2724.7 to 4221.2)
7vPnC - Serotype 18C (N=111, 111)	8548 (3544.8 to 5219.1)	8223 (6999.1 to 9661)
7vPnC - Serotype 19F (N=107, 110)	889 (7293.5 to 10017.2)	1561 (1264 to 1927.6)
7vPnC - Serotype 23F (N=110, 111)	5223 (698.5 to 1130.2)	4992 (3931.4 to 6337.5)
Additional - Serotype 1 (N=112, 111)	4 (-99999 to 99999)	98 (79.6 to 121.8)
Additional - Serotype 3 (N=115, 115)	5 (4.1 to 5)	339 (300.7 to 382.6)
Additional - Serotype 5 (N=113, 112)	4 (3.9 to 4.2)	218 (183.4 to 260.3)
Additional - Serotype 6A (N=105, 110)	491 (309.4 to 778.7)	4230 (3457 to 5175.3)
Additional - Serotype 7F (N=102, 113)	6 (4.4 to 7.3)	3622 (3218.7 to 4075.7)
Additional - Serotype 19A (N=108, 110)	11 (8 to 15.5)	644 (512 to 810.4)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPA GMTs were significantly higher in 13vPnC Group 2 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

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

0.69

upper limit

1.21

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

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

0.65

upper limit

1.34

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

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

0.59

upper limit

1.05

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

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

0.63

upper limit

1.33

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.2

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

1.39

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

1.28

upper limit

2.41

Statistical analysis for Additional - serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

24.6

Confidence interval

level

95%

sides

2-sided

lower limit

19.95

upper limit

30.39

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

75.1

Confidence interval

level

95%

sides

2-sided

lower limit

63.9

upper limit

88.19

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

53.5

Confidence interval

level

95%

sides

2-sided

lower limit

44.81

upper limit

63.96

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

8.6

Confidence interval

level

95%

sides

2-sided

lower limit

5.26

upper limit

14.11

Statistical analysis for Additional - serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

57.8

Confidence interval

level

95%

sides

2-sided

lower limit

38.85

upper limit

85.87

Statistical analysis for Additional- serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

892

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

642.4

Confidence interval

level

95%

sides

2-sided

lower limit

491.58

upper limit

839.53

Secondary: Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 3 vs 7vPnC Group 1

Top of page

End point title

Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 3 vs 7vPnC Group 1 ^[76]

End point description

A randomly selected subset was analyzed for serum OPA GMT elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1, blood samples were collected at the 6-, 12-, and 13- month visits. For Group 3 subjects, blood samples were collected at the 7-, 12-, and 13 month visits. In the below table 'N' represents the number of subjects with a determinate antibody titer for the specified serotype. Evaluable infant pneumococcal immunogenicity population included participants aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation. Here 99999 and -99999 in 95 percent (%) Confidence interval signifies not estimable.

End point type

Secondary

End point timeframe

1 month after the infant series (7 months of age)

Notes
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	446	440
Units: GMT
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=112, 110)	4650 (3804.6 to 5682.5)	3470 (2767.3 to 4350.3)
7vPnC - Serotype 6B (N=114, 101)	3725 (2834.3 to 4894.7)	2402 (1778.5 to 3244.1)
7vPnC - Serotype 9V (N=110,99)	2727 (2097.7 to 3544.5)	2294 (1695.6 to 3103.2)
7vPnC - Serotype 14 (N=110, 96)	4301 (3544.8 to 5219.1)	2288 (1783.6 to 2935.5)
7vPnC - Serotype 18C (N=111,98)	8548 (7293.5 to 10017.2)	8692 (7071.3 to 10684.3)
7vPnC - Serotype 19F (N=107,97)	889 (698.5 to 1130.2)	1087 (855.6 to 1382.2)
7vPnC - Serotype 23F (N=110,98)	5223 (3890.2 to 7011.5)	3608 (2608.1 to 4990.3)
Additional - Serotype 1 (N=112, 98)	4 (-99999 to 99999)	132 (103.8 to 166.7)
Additional - Serotype 3 (N=114, 102)	5 (4.1 to 5)	209 (180.6 to 241.1)
Additional - Serotype 5 (N=113, 101)	4 (3.9 to 4.2)	234 (184.5 to 297.2)
Additional - Serotype 6A (N=105,97)	491 (309.4 to 778.7)	3518 (2781.7 to 4450)
Additional - Serotype 7F (N=102, 100)	6 (4.4 to 7.3)	4164 (3591 to 4828.9)
Additional - Serotype 19A (N=108,98)	11 (8 to 15.5)	529 (407.7 to 687.3)

Statistical analysis for 7vPnC - serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPA GMTs were significantly higher in 13vPnC Group 3 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

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

0.55

upper limit

1.01

Statistical analysis for 7vPnC - serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.6

Confidence interval

level

90%

sides

2-sided

lower limit

0.43

upper limit

0.96

Statistical analysis for 7vPnC - serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

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

0.57

upper limit

1.25

Statistical analysis for 7vPnC - serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

0.72

Statistical analysis for 7vPnC - serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

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

1.31

Statistical analysis for 7vPnC - serotype 19F

Statistical analysis description

Comparison groups

13vPnC Group 3 v 7vPnC Group 1

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.72

Statistical analysis for 7vPnC serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

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

0.45

upper limit

1.07

Statistical analysis for Additional - serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

32.9

Confidence interval

level

95%

sides

2-sided

lower limit

26.38

upper limit

40.97

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

46.2

Confidence interval

level

95%

sides

2-sided

lower limit

38.7

upper limit

55.14

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

57.4

Confidence interval

level

95%

sides

2-sided

lower limit

45.69

upper limit

72.05

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

7.2

Confidence interval

level

95%

sides

2-sided

lower limit

4.23

upper limit

12.15

Statistical analysis for Additional- serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

738.6

Confidence interval

level

95%

sides

2-sided

lower limit

551.83

upper limit

988.55

Statistical analysis for Additional- Serotype 19F

Statistical analysis description

Comparison groups

13vPnC Group 3 v 7vPnC Group 1

Number of subjects included in analysis

886

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT Ratio

Point estimate

47.5

Confidence interval

level

95%

sides

2-sided

lower limit

31.13

upper limit

72.38

Secondary: Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 4 vs 7vPnC Group 1

Top of page

End point title

Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 4 vs 7vPnC Group 1 ^[77]

End point description

A randomly selected subset was analyzed for serum OPA GMT elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Group 1, blood samples were collected at the 6-, 12-, and 13- month visits. For Group 4 subjects, blood samples were collected at the 6-, 12-, and 13 month visits. In the below table 'N' represents the number of subjects with a determinate antibody titer for the specified serotype. Evaluable infant pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after infant series within the required time frame, received no prohibited vaccines and had no major protocol deviation. Here 99999 and -99999 in the confidence interval signifies not estimable.

End point type

Secondary

End point timeframe

1 month after the infant series (6 months of age)

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	446	224
Units: GMT
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=112, 101)	4650 (3804.6 to 5682.5)	3546 (2726.6 to 4611.9)
7vPnC - Serotype 6B (N=114,99)	3725 (2834.3 to 4894.7)	452 (269.7 to 756.9)
7vPnC - Serotype 9V (N=110,99)	2727 (2097.7 to 3544.5)	1439 (945 to 2191.5)
7vPnC - Serotype 14 (N=110, 101)	4301 (3544.8 to 5219.1)	3101 (2436.8 to 3945.2)
7vPnC - Serotype 18C (N=111,103)	8548 (7293.5 to 10017.2)	4742 (3715.6 to 6052.4)
7vPnC - Serotype 19F (N=107,98)	889 (698.5 to 1130.2)	1283 (999.3 to 1646.8)
7vPnC - Serotype 23F (N=110,102)	5223 (3890.2 to 7011.5)	2708 (1917.4 to 3825.4)
Additional - Serotype 1 (N=112,95)	4 (-99999 to 99999)	95 (75.7 to 118.5)
Additional - Serotype 3 (N=115,107)	5 (4.1 to 5)	268 (232.9 to 308.8)
Additional - Serotype 5 (N=113, 104)	4 (3.9 to 4.2)	203 (164.4 to 249.6)
Additional - Serotype 6A (N=105, 102)	491 (309.4 to 778.7)	2486 (1978.1 to 3124.2)
Additional - Serotype 7F (N=102, 104)	6 (4.4 to 7.3)	3527 (3054.8 to 4072.8)
Additional - Serotype 19A (N=108, 102)	11 (8 to 15.5)	447 (327.1 to 611.6)

Statistical analysis for Serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPA GMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

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

0.55

upper limit

1.06

Statistical analysis for Serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

0.21

Statistical analysis for Serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

0.85

Statistical analysis for Serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

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

0.53

upper limit

0.98

Statistical analysis for Serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

0.74

Statistical analysis for Serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

2.04

Statistical analysis for Serotypec 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.33

upper limit

0.81

Statistical analysis for Additional serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

23.7

Confidence interval

level

95%

sides

2-sided

lower limit

19.15

upper limit

29.27

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

59.4

Confidence interval

level

95%

sides

2-sided

lower limit

49.81

upper limit

70.74

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

5.1

Confidence interval

level

95%

sides

2-sided

lower limit

3.02

upper limit

8.49

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

49.6

Confidence interval

level

95%

sides

2-sided

lower limit

40.49

upper limit

60.81

Statistical analysis for Additional serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

40.1

Confidence interval

level

95%

sides

2-sided

lower limit

25.54

upper limit

62.98

Statistical analysis for Additional serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

670

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

625.6

Confidence interval

level

95%

sides

2-sided

lower limit

469.5

upper limit

833.19

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Top of page

End point title

GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1 ^[78]

End point description

Antibody GMC for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC and corresponding 2-sided 95% CIs were evaluated. GMs were calculated using all subjects with available data for the specified blood draw. In the below table 'N' represents the number of subjects with a determinate antibody concentration for the specified serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	399	409
Units: mcg/mL
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=399,409)	14.88 (13.64 to 16.25)	12.75 (11.64 to 13.96)
7vPnC - Serotype 6B (N=399, 409)	11.94 (10.82 to 13.18)	11.64 (10.46 to 12.95)
7vPnC - Serotype 9V (N=399, 409, )	8.36 (7.7 to 9.08)	6.79 (6.24 to 7.38)
7vPnC - Serotype 14 (N= 399,409)	24.55 (22.71 to 26.55)	21.79 (20.13 to 23.6)
7vPnC - Serotype 18C (N=399, 409)	9.02 (8.29 to 9.82)	8.96 (8.22 to 9.76)
7vPnC - Serotype 19F (N=399, 409)	11.36 (10.36 to 12.46)	18.02 (16.48 to 19.7)
7vPnC - Serotype 23F (N=399, 409)	12.61 (11.34 to 14.03)	12.15 (10.82 to 13.65)
Additional - Serotype 1 (N=347,409)	0.06 (0.05 to 0.07)	11.77 (10.62 to 13.03)
Additional - Serotype 3 (N=347,409)	0.14 (0.12 to 0.16)	1.73 (1.62 to 1.85)
Additional - Serotype 5 (N= 398,409)	0.67 (0.61 to 0.74)	8.05 (7.4 to 8.75)
Additional - Serotype 6A (N=399,409)	3.02 (2.68 to 3.4)	11.21 (10.18 to 12.35)
Additional - Serotype 7F (N=394,409)	0.1 (0.08 to 0.12)	9.73 (8.92 to 10.61)
Additional - Serotype 19A (N=399,409)	2.48 (2.27 to 2.7)	15.27 (13.99 to 16.67)

Statistical analysis for Serotype 4

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.97

Statistical analysis for Serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.13

Statistical analysis for Serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.81

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

0.91

Statistical analysis for Serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

0.99

Statistical analysis for Serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.12

Statistical analysis for Serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

1.39

upper limit

1.8

Statistical analysis for Serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.13

Statistical analysis for additional Serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

200.98

Confidence interval

level

95%

sides

2-sided

lower limit

160.75

upper limit

251.28

Statistical analysis for additional Serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

12.22

Confidence interval

level

95%

sides

2-sided

lower limit

10.58

upper limit

14.12

Statistical analysis for additional Serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

11.98

Confidence interval

level

95%

sides

2-sided

lower limit

10.54

upper limit

13.62

Statistical analysis for additional Serotype 6A

Statistical analysis description

Comparison groups

13vPnC Group 2 v 7vPnC Group 1

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

3.71

Confidence interval

level

95%

sides

2-sided

lower limit

3.19

upper limit

4.32

Statistical analysis for additional Serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

96.93

Confidence interval

level

95%

sides

2-sided

lower limit

80.28

upper limit

117.04

Statistical analysis for additional Serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

6.17

Confidence interval

level

95%

sides

2-sided

lower limit

5.4

upper limit

6.97

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Top of page

End point title

GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1 ^[79]

End point description

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[79] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	399	423
Units: mcg/mL
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=399,423)	14.88 (13.64 to 16.25)	13.25 (12.19 to 14.4)
7vPnC - Serotype 6B (N=399,423)	11.94 (10.82 to 13.18)	13.05 (11.88 to 14.35)
7vPnC - Serotype 9V (N=399,423)	8.36 (7.7 to 9.08)	7.04 (6.48 to 7.65)
7vPnC - Serotype 14 (N=423,399)	24.55 (22.71 to 26.55)	20.61 (19.04 to 22.31)
7vPnC - Serotype 18C (N=423,399)	9.02 (8.29 to 9.82)	11.38 (10.49 to 12.34)
7vPnC - Serotype 19F (N=399,423)	11.36 (10.36 to 12.46)	15.96 (14.57 to 17.47)
7vPnC - Serotype 23F (N=399,423)	12.61 (11.34 to 14.03)	13.9 (12.42 to 15.55)
Additional - Serotype 1 (N=423,347)	0.06 (0.05 to 0.07)	11.86 (10.84 to 12.98)
Additional - Serotype 3 (N=370, 421)	0.14 (0.12 to 0.16)	1.41 (1.33 to 1.5)
Additional - Serotype 5 (N=423, 398)	0.67 (0.61 to 0.74)	8.27 (7.62 to 8.97)
Additional - Serotype 6A (N= 423,399)	3.02 (2.68 to 3.4)	14.08 (12.83 to 15.45)
Additional - Serotype 7F (N=394,423)	0.1 (0.08 to 0.12)	13.11 (11.99 to 14.33)
Additional - Serotype 19A (N=399,423)	2.48 (2.27 to 2.7)	14.19 (13.11 to 15.35)

Statistical analysis for serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. GMCsnwere significantly higher in 13vPnC Group 3 than 7vPnC Group 1 if lower bound of 95% CI GMC ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

Statistical analysis for serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

1.25

Statistical analysis for serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.95

Statistical analysis for Serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.95

Statistical analysis for Serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.12

upper limit

1.42

Statistical analysis for Serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.23

upper limit

1.6

Statistical analysis for Serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.29

statistical analysis for Additional serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

202.59

Confidence interval

level

95%

sides

2-sided

lower limit

163.4

upper limit

251.18

statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

9.96

Confidence interval

level

95%

sides

2-sided

lower limit

8.67

upper limit

11.46

statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

12.32

Confidence interval

level

95%

sides

2-sided

lower limit

10.86

upper limit

13.98

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

4.66

Confidence interval

level

95%

sides

2-sided

lower limit

4.01

upper limit

5.41

Statistical analysis for Additional serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

130.55

Confidence interval

level

95%

sides

2-sided

lower limit

108.16

upper limit

157.58

Statistical analysis for Additional serotype 19A

Statistical analysis description

Comparison groups

13vPnC Group 3 v 7vPnC Group 1

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

5.73

Confidence interval

level

95%

sides

2-sided

lower limit

5.1

upper limit

6.44

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Top of page

End point title

GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1 ^[80]

End point description

Antibody GMC for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC and corresponding 2-sided 95% CIs were evaluated. GMs were calculated using all subjects with available data for the specified blood draw. In the below table 'N' represents the number of subjects with a determinate antibody concentration for the specified serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	399	215
Units: mcg/mL
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=399, 215)	14.88 (11.34 to 14.03)	12.15 (10.8 to 13.67)
7vPnC - Serotype 6B (N=399, 215)	11.94 (0.05 to 0.07)	11.92 (10.28 to 13.81)
7vPnC - Serotype 9V (N= 399, 215)	8.36 (0.12 to 0.16)	7.23 (6.49 to 8.06)
7vPnC - Serotype 14 (N=399, 215)	24.55 (0.61 to 0.67)	23.45 (21.08 to 26.09)
7vPnC - Serotype 18C (N= 399, 215)	9.02 (2.68 to 3.4)	8.79 (7.73 to 9.99)
7vPnC - Serotype 19F (N=399, 215)	11.36 (0.08 to 0.12)	22.13 (19.63 to 24.95)
7vPnC - Serotype 23F (N=399, 215)	12.61 (2.27 to 2.7)	9.81 (8.4 to 11.45)
Additional - Serotype 1 (N=347, 215)	0.06 (13.64 to 16.25)	12.55 (11.15 to 14.12)
Additional - Serotype 3 (N= 370, 213)	0.14 (10.82 to 13.18)	1.63 (1.49 to 1.79)
Additional - Serotype 5 (N=398, 215)	0.67 (7.7 to 9.08)	7.9 (7.15 to 8.72)
Additional - Serotype 6A (N=399, 215)	3.02 (22.71 to 26.55)	14.18 (12.57 to 16.01)
Additional - Serotype 7F (N=394, 215)	0.1 (8.29 to 9.82)	10.11 (9.06 to 11.28)
Additional - Serotype 19A (N=399, 215)	2.48 (10.36 to 12.46)	16.71 (14.86 to 18.78)

Statistical analysis for serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. GMCs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMC ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.82

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

0.95

Statistical analysis for serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.19

Statistical analysis for serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.19

Statistical analysis for serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.99

Statistical analysis for serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.12

Statistical analysis for serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

1.39

upper limit

1.8

Statistical analysis for serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.13

Statistical analysis for Additional serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

200.98

Confidence interval

level

95%

sides

2-sided

lower limit

160.75

upper limit

251.28

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

12.22

Confidence interval

level

95%

sides

2-sided

lower limit

10.58

upper limit

14.12

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

11.98

Confidence interval

level

95%

sides

2-sided

lower limit

10.54

upper limit

13.62

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

3.71

Confidence interval

level

95%

sides

2-sided

lower limit

3.19

upper limit

4.32

Statistical analysis for Additional serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

96.93

Confidence interval

level

95%

sides

2-sided

lower limit

80.28

upper limit

117.04

Statistical analysis for Additional serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMC ratio

Point estimate

6.17

Confidence interval

level

95%

sides

2-sided

lower limit

5.46

upper limit

6.97

Secondary: Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Top of page

End point title

Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 2 vs 7vPnC Group 1 ^[81]

End point description

A randomly selected subset was analyzed for serum OPA elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1 and 2, blood samples (approximately 5 mL) were collected at the 6-, 12-, and 13-month visits. In the below table N = number of subjects with a determinate OPA antibody titer to the given serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	399	409
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N= 113, 109)	100 (96.8 to 100)	100 (96.7 to 100)
7vPnC - Serotype 6B (N=111, 109)	99.1 (95.1 to 100)	98.2 (93.5 to 99.8)
7vPnC - Serotype 9V (N=113, 109)	100 (96.8 to 100)	100 (96.7 to 100)
7vPnC - Serotype 14 (N=112, 109)	100 (96.8 to 100)	100 (96.7 to 100)
7vPnC - Serotype 18C (N=111, 110)	100 (96.7 to 100)	100 (96.7 to 100)
7vPnC - Serotype 19F (N=112,106)	97.3 (92.4 to 99.4)	98.1 (93.4 to 99.8)
7vPnC - Serotype 23F (N= 112,108)	100 (96.8 to 100)	100 (96.6 to 100)
Additional - Serotype 1 (N=113,108)	2.7 (0.6 to 7.6)	97.2 (92.1 to 99.4)
Additional - Serotype 3 (N=113,110)	24.8 (17.1 to 33.8)	99.1 (95 to 100)
Additional - Serotype 5 (N=113,111)	0.9 (0 to 4.8)	98.2 (93.6 to 99.8)
Additional - Serotype 6A (N=111,108)	96.4 (91 to 99)	99.1 (94.9 to 100)
Additional - Serotype 7F (N=92,108)	27.2 (18.4 to 37.4)	100 (96.6 to 100)
Additional - Serotype 19A (N=106, 106)	67 (57.2 to 75.8)	99.1 (94.9 to 100)

Statistical analysis for serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for serotype 6B

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

3.3

Statistical analysis for serotype 9V

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for serotype 14

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for serotype 18C

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for serotype 19F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

5.9

Statistical analysis for serotype 23F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for Additional serotype 3

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

74.3

Confidence interval

level

95%

sides

2-sided

lower limit

65.2

upper limit

82.1

Statistical analysis for Additional serotype 5

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

97.3

Confidence interval

level

95%

sides

2-sided

lower limit

92.3

upper limit

99.4

Statistical analysis for Additional serotype 6A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

8.1

Statistical analysis for Additional serotype 7F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

72.8

Confidence interval

level

95%

sides

2-sided

lower limit

62.6

upper limit

81.6

Statistical analysis for Additional serotype 19A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Median difference (final values)

Point estimate

32.1

Confidence interval

level

95%

sides

2-sided

lower limit

23.1

upper limit

41.9

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Top of page

End point title

Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 3 vs 7vPnC Group 1 ^[82]

End point description

A randomly selected subset was analyzed for serum OPA elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Group 1, blood samples were collected at the 6-, 12-, and 13-month visits. For Group 3 subjects , blood samples were collected at the 7-, 12-, and 13 month visits. In the below table N = number of subjects with a determinate OPA antibody titer to the given serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	399	423
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=113, 105)	100 (96.8 to 100)	100 (96.5 to 100)
7vPnC - Serotype 6B (N=111, 103)	99.1 (95.1 to 100)	100 (96.5 to 100)
7vPnC - Serotype 9V (N=113, 105)	100 (96.8 to 100)	100 (96.5 to 100)
7vPnC - Serotype 14 (N=112, 106)	100 (96.7 to 100)	100 (96.6 to 100)
7vPnC - Serotype 18C (N=111, 106)	100 (96.7 to 100)	100 (96.6 to 100)
7vPnC - Serotype 19F (N=112,101)	97.3 (92.4 to 99.4)	100 (96.4 to 100)
7vPnC - Serotype 23F (N=112, 103)	100 (96.8 to 100)	97.1 (91.7 to 99.4)
Additional - Serotype 1 (N=113, 105)	2.7 (0.6 to 7.6)	99 (94.8 to 100)
Additional - Serotype 3 (N=113, 107)	24.8 (17.1 to 33.8)	100 (96.6 to 100)
Additional - Serotype 5 (N=113, 105)	0.9 (0 to 4.8)	99 (94.8 to 100)
Additional - Serotype 6A (N=111,105)	96.4 (91 to 99)	100 (96.5 to 100)
Additional - Serotype 7F (N= 92,104)	27.2 (18.4 to 37.4)	100 (96.5 to 100)
Additional - Serotype 19A (N=106, 105)	67 (57.2 to 75.8)	100 (96.5 to 100)

Statistical analysis for Serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other ^[83]

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

3.3

Notes
[83] - CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed aspercentage.

Statistical analysis for Serotype 6B

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other ^[84]

Method

Parameter type

Mean difference (final values)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.9

upper limit

4.9

Notes
[84] - CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed aspercentage.

Statistical analysis for Serotype 9V

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other ^[85]

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.5

upper limit

3.3

Notes
[85] - CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed aspercentage.

Statistical analysis for Serotype 14

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for Serotype 18C

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for serotype 19F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.2

upper limit

5.9

Statistical analysis for serotype 23F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for Additional serotype 1

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

94.6

Confidence interval

level

95%

sides

2-sided

lower limit

88.3

upper limit

Statistical analysis for Additional serotype 3

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

74.3

Confidence interval

level

95%

sides

2-sided

lower limit

65.2

upper limit

82.1

Statistical analysis for Additional serotype 5

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

97.3

Confidence interval

level

95%

sides

2-sided

lower limit

92.3

upper limit

99.4

Statistical analysis for Additional serotype 6A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

8.1

Statistical analysis for Additional serotype 7F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

72.8

Confidence interval

level

95%

sides

2-sided

lower limit

62.6

upper limit

81.6

Statistical analysis for Additional serotype 19A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Mean difference (final values)

Point estimate

32.1

Confidence interval

level

95%

sides

2-sided

lower limit

23.1

upper limit

41.9

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Top of page

End point title

Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 4 vs 7vPnC Group 1 ^[86]

End point description

A randomly selected subset was analyzed for serum OPA elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1, blood samples were collected at the 6-, 12-, and 13-month visits. For Group 4 subjects, blood samples were collected at the 6-, 12-, and 13 month visits. In the below table N = number of subjects with a determinate OPA antibody titer to the given serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	399	215
Units: percentage of subjects
number (confidence interval 95%)
7vPnC - Serotype 4 (N=113, 108)	100 (96.8 to 100)	100 (96.6 to 100)
7vPnC - Serotype 6B (N=111, 103)	99.1 (95.1 to 100)	96.1 (90.4 to 98.9)
7vPnC - Serotype 9V (N= 113, 107)	100 (96.8 to 100)	99.1 (94.9 to 100)
7vPnC - Serotype 14 (N=112, 107)	100 (96.8 to 100)	100 (96.6 to 100)
7vPnC - Serotype 18C (N=111, 113)	100 (96.7 to 100)	100 (96.8 to 100)
7vPnC - Serotype 19F (N=112, 106)	97.3 (92.4 to 99.4)	100 (96.6 to 100)
7vPnC - Serotype 23F (N= 112, 104)	100 (96.8 to 100)	95.2 (89.1 to 98.4)
Additional - Serotype 1 (N=113, 117)	2.7 (0.6 to 7.6)	98.3 (94 to 99.8)
Additional - Serotype 3 (N=113,118)	24.8 (17.1 to 33.8)	99.2 (95.4 to 100)
Additional - Serotype 5 (N=113,118)	0.9 (0 to 4.8)	99.2 (95.4 to 100)
Additional - Serotype 6A (N=111,108)	96.4 (91 to 99)	100 (96.6 to 100)
Additional - Serotype 7F (N=92,115)	27.2 (18.4 to 37.4)	99.1 (95.3 to 100)
Additional - Serotype 19A (N=106,113)	67 (57.2 to 75.8)	99.1 (95.2 to 100)

Statistical analysis for Serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for Serotype 4

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

1.6

Statistical analysis for Serotype 9V

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.1

upper limit

2.4

Statistical analysis for Serotype 14

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

3.3

Statistical analysis for Serotype 18C

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

3.3

Statistical analysis for Serotype 19F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

7.6

Statistical analysis for Serotype 23F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-10.9

upper limit

-1

Statistical analysis for additional Serotype 1

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

95.6

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

98.6

Statistical analysis for additional Serotype 3

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

74.4

Confidence interval

level

95%

sides

2-sided

lower limit

65.3

upper limit

82.1

Statistical analysis for additional Serotype 5

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

98.3

Confidence interval

level

95%

sides

2-sided

lower limit

93.9

upper limit

99.8

Statistical analysis for additional Serotype 6B

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

3.3

Statistical analysis for Additional serotype 7F

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

13vPnC Group 4 v 7vPnC Group 1

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

61.7

upper limit

80.7

Statistical analysis for Additional serotype 19A

Statistical analysis description

CI for the difference in proportions is computed using the Chan and Zhang procedure, 13vPnC-7vPnC reference, expressed as percentage.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Mean difference (final values)

Point estimate

32.1

Confidence interval

level

95%

sides

2-sided

lower limit

23.2

upper limit

41.9

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Top of page

End point title

Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1 ^[87]

End point description

A randomly selected subset was analyzed for serum OPA GMT elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Groups 1 and 2, blood samples (approximately 5 mL) were collected at the 6-, 12-, and 13-month visits. In the below table 'N' represents the number of subjects with a determinate antibody titer for the specified serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 2
Number of subjects analysed	399	409
Units: GMT
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=113, 109)	7662 (6171.2 to 9513.2)	6915 (5700.3 to 8389.1)
7vPnC - Serotype 6B (N=111,109)	4958 (3931.7 to 6251.5)	4894 (3695.5 to 6481.9)
7vPnC - Serotype 9V (N= 113,109)	7825 (6469.6 to 9463.4)	7679 (6251.4 to 9433.6)
7vPnC - Serotype 14 (N=112, 109)	3269 (2773 to 3854.4)	2694 (2248.9 to 3226.7)
7vPnC - Serotype 18C (N=111,110)	22011 (18687.5 to 25925.5)	20661 (16762.4 to 25467)
7vPnC - Serotype 19F (N=112,106)	1410 (1066.7 to 1864.3)	3860 (2897.1 to 5144)
7vPnC - Serotype 23F (N=112,108)	13098 (10963.1 to 15648.6)	11141 (8895.2 to 13953.7)
Additional - Serotype 1 (N=113,108)	4 (3.9 to 4.8)	372 (299.8 to 460.7)
Additional - Serotype 3 (N=113,110)	7 (5.8 to 8.8)	289 (246.8 to 338.5)
Additional - Serotype 5 (N=113,111)	4 (3.9 to 4.8)	656 (527.7 to 816.5)
Additional - Serotype 6A (N=111,108)	2569 (1879.1 to 3511.4)	10013 (7740.8 to 12952)
Additional - Serotype 7F (N=92,108)	17 (10.5 to 28.8)	5141 (4373.1 to 6044.1)
Additional - Serotype 19A (N=106,106)	48 (32.4 to 70.4)	1713 (1382.2 to 2124)

statistical analysis for serotype 4

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

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

0.68

upper limit

1.21

Statistical analysis for serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.42

Statistical analysis for serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

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

1.3

Statistical analysis for serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

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

0.65

upper limit

1.05

Statistical analysis for serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

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

0.72

upper limit

1.22

Statistical analysis for serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

1.84

upper limit

4.08

Statistical analysis for serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

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

0.64

upper limit

1.13

Statistical analysis for Additional serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

85.9

Confidence interval

level

95%

sides

2-sided

lower limit

68.25

upper limit

108.01

Statistical analysis for Additional serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

40.6

Confidence interval

level

95%

sides

2-sided

lower limit

31.26

upper limit

52.74

Statistical analysis for Additional serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

160.3

Confidence interval

level

95%

sides

2-sided

lower limit

128.62

upper limit

199.75

Statistical analysis for Additional serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

3.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

5.84

Statistical analysis for Additional serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

296.1

Confidence interval

level

95%

sides

2-sided

lower limit

180.45

upper limit

485.91

Statistical analysis for Additional serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 2

Number of subjects included in analysis

808

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

35.9

Confidence interval

level

95%

sides

2-sided

lower limit

23.09

upper limit

55.68

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Top of page

End point title

Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1 ^[88]

End point description

A randomly selected subset was analyzed for serum OPA GMT elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Group 1, blood samples were collected at the 6-, 12-, and 13- month visits. For Group 3 subjects, blood samples were collected at the 7-, 12-, and 13 month visits. In the below table 'N' represents the number of subjects with a determinate antibody titer for the specified serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 3
Number of subjects analysed	399	423
Units: GMT
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N= 113, 105)	7662 (32.4 to 70.4)	7319 (5960.5 to 8988)
7vPnC - Serotype 6B (N= 111,103)	4958 (6171.2 to 9513.2)	5740 (4723.9 to 6975.2)
7vPnC - Serotype 9V (N=113,105)	7825 (3931.7 to 6251.5)	8892 (7563.3 to 10452.9)
7vPnC - Serotype 14 (N= 112,106)	3269 (6469.6 to 9463.4)	2776 (2268.6 to 3396.8)
7vPnC - Serotype 18C (N= 111, 106)	22011 (2773 to 3854.4)	20098 (17265.9 to 23393.5)
7vPnC - Serotype 19F (N=112, 101)	1410 (18687.5 to 25925.5)	4513 (3685.1 to 5528.1)
7vPnC - Serotype 23F (N=112, 103)	13098 (1066.7 to 1864.3)	9845 (7137.2 to 13578.9)
Additional - Serotype 1 (N=113, 105)	4 (10963.1 to 15648.6)	424 (349 to 516.1)
Additional - Serotype 3 (N=113, 107)	7 (3.9 to 4.8)	309 (269 to 354.8)
Additional - Serotype 5 (N=113, 105)	4 (5.8 to 8.8)	727 (592.6 to 891.6)
Additional - Serotype 6A (N= 111,105)	2569 (3.9 to 4.3)	11347 (9501.1 to 13551.5)
Additional - Serotype 7F (N=92,104)	17 (1879.1 to 3511.4)	7123 (6163.8 to 8230.9)
Additional - Serotype 19A (N=106,105)	48 (10.5 to 28.8)	2041 (1753.6 to 2376.4)

Statistical analysis for serotype 4

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.29

Statistical analysis for serotype 6B

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

1.57

Statistical analysis for Serotype 9V

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

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

0.88

upper limit

1.46

Statistical analysis for Serotype 18C

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

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

0.73

upper limit

1.14

Statistical analysis for Serotype 14

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

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

0.66

upper limit

1.1

Statistical analysis for Serotype 19F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

2.26

upper limit

4.45

Statistical analysis for Serotype 23F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

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

0.53

upper limit

1.07

Statistical analysis for additional Serotype 1

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

98.1

Confidence interval

level

95%

sides

2-sided

lower limit

79.41

upper limit

121.08

Statistical analysis for additional Serotype 5

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

177.5

Confidence interval

level

95%

sides

2-sided

lower limit

145.12

upper limit

217.11

Statistical analysis for additional Serotype 3

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

43.4

Confidence interval

level

95%

sides

2-sided

lower limit

33.73

upper limit

55.85

Statistical analysis for additional Serotype 6A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

4.4

Confidence interval

level

95%

sides

2-sided

lower limit

3.07

upper limit

6.35

Statistical analysis for additional Serotype 7F

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

410.2

Confidence interval

level

95%

sides

2-sided

lower limit

249.67

upper limit

674.1

Statistical analysis for additional Serotype 19A

Statistical analysis description

Comparison groups

7vPnC Group 1 v 13vPnC Group 3

Number of subjects included in analysis

822

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

GMT ratio

Point estimate

42.7

Confidence interval

level

95%

sides

2-sided

lower limit

28.22

upper limit

64.69

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Top of page

End point title

Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1 ^[89]

End point description

A randomly selected subset was analyzed for serum OPA GMT elicited by the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). For subjects in Group1 1, blood samples were collected at the 6-, 12-, and 13- month visits. For Group 4 subjects, blood samples were collected at the 6-, 12-, and 13 month visits. In the below table 'N' represents the number of subjects with a determinate antibody titer for the specified serotype. Evaluable toddler pneumococcal immunogenicity population included subjects aged 41 to 78 days, received vaccinations as they were randomized to receive, had valid and determinate pneumococcal assay result, had blood draw after toddler dose within the required time frame, received no prohibited vaccines and had no major protocol deviation.

End point type

Secondary

End point timeframe

1 month after the toddler dose (13 Months of age)

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The end point is not reporting statistics for all the arms in the baseline period.

End point values	7vPnC Group 1	13vPnC Group 4
Number of subjects analysed	399	215
Units: GMT
geometric mean (confidence interval 95%)
7vPnC - Serotype 4 (N=113, 108)	7662 (3931.7 to 6251.5)	7193 (5716.6 to 9049.6)
7vPnC - Serotype 6B (N=111,103)	4958 (6469.6 to 9463.4)	2713 (1973.3 to 3729.5)
7vPnC - Serotype 9V (N=113, 107)	7825 (2773 to 3854.4)	7861 (6237.6 to 9907.1)
7vPnC - Serotype 14 (N=112, 107)	3269 (18687.5 to 25925.5)	2928 (2481.8 to 3453.7)
7vPnC - Serotype 18C (N=111, 113)	22011 (6171.2 to 9513.2)	18425 (15495.1 to 21909)
7vPnC - Serotype 19F (N=112, 106)	1410 (1066.7 to 1864.3)	3636 (3046.5 to 4340)
7vPnC - Serotype 23F (N=112, 104)	13098 (10963.1 to 15648.6)	6255 (4289.5 to 9120.3)
Additional - Serotype 1 (N=113,117)	4 (3.9 to 4.8)	391 (317.7 to 480.4)
Additional - Serotype 3 (N=113,118)	7 (5.8 to 8.8)	351 (305.5 to 402.9)
Additional - Serotype 5 (N=113,118)	4 (3.9 to 4.3)	661 (547.7 to 797.8)
Additional - Serotype 6A (N=111,108)	2569 (1879.1 to 3511.4)	7755 (6548.9 to 9184)
Additional - Serotype 7F (N=92,115)	17 (10.5 to 28.8)	5700 (4741.5 to 6853.3)
Additional - Serotype 19A (N=106,113)	48 (32.4 to 70.4)	1503 (1209.3 to 1868.5)

Statistical analysis for serotype 4

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.69

upper limit

1.28

Statistical analysis for serotype 6B

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.37

upper limit

0.81

Statistical analysis for serotype 9V

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.13

Statistical analysis for serotype 14

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.13

Statistical analysis for serotype 18C

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.66

upper limit

11.06

Statistical analysis for serotype 19F

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.85

upper limit

3.6

Statistical analysis for serotype 23F

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

0.72

Statistical analysis for additional serotype 1

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

90.3

Confidence interval

level

95%

sides

2-sided

lower limit

71.82

upper limit

113.42

Statistical analysis for additional serotype 3

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

49.3

Confidence interval

level

95%

sides

2-sided

lower limit

38.49

upper limit

63.12

Statistical analysis for additional serotype 5

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

161.4

Confidence interval

level

95%

sides

2-sided

lower limit

132.63

upper limit

196.46

Statistical analysis for additional serotype 6A

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

2.11

upper limit

4.31

Statistical analysis for additional serotype 7F

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

328.3

Confidence interval

level

95%

sides

2-sided

lower limit

200.4

upper limit

537.89

Statistical analysis for additional serotype 19A

Statistical analysis description

CIs of ratio are back transformations of CI based on Student t distribution for mean difference of logarithms of measures. OPAGMTs were significantly higher in 13vPnC Group 4 than 7vPnC Group 1 if lower bound of 95% CI GMT ratios >1.

Comparison groups

7vPnC Group 1 v 13vPnC Group 4

Number of subjects included in analysis

614

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

GMT ratio

Point estimate

31.5

Confidence interval

level

95%

sides

2-sided

lower limit

20.37

upper limit

48.58

Adverse events

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Timeframe for reporting adverse events

AEs/ SAEs: recorded from informed consent till the end of study (up to 18 months of age).Subjects recorded prespecified AEs in electronic diary:local reactions; systemic events; (within 7 days post 13vPnC or 7vPnc dose for infant and toddler doses).

Adverse event reporting additional description

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

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

17.0

Reporting group title

7vPnC Group 1

Reporting group description

Subjects received 7vPnC vaccine administered at 3, 4, 5, and 12 months of age. Single dose (0.5 mL) of 7vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

Reporting group title

13vPnC Group 2

Reporting group description

Subjects received 13vPnC vaccine administered at 3, 4, 5, and 12 months of age. Single dose (0.5 mL) of 13vPnCwas administered intramuscularly into the anterolateral muscle of the left thigh.

Reporting group title

13vPnC Group 3

Reporting group description

Subjects received 13vPnC vaccine administered at 2, 4, 6, and 12 months of age. Single dose (0.5 mL) of 13vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

Reporting group title

13vPnC Group 4

Reporting group description

Subjects received 13vPnC vaccine administered at 3, 5, and 12 months of age. Single dose (0.5 mL) of 13vPnC was administered intramuscularly into the anterolateral muscle of the left thigh.

Serious adverse events	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 472 (1.27%)	10 / 472 (2.12%)	11 / 474 (2.32%)	5 / 234 (2.14%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangioma
subjects affected / exposed ^[1]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Cerebral palsy
subjects affected / exposed ^[2]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Heart disease congenital
subjects affected / exposed ^[3]	0 / 472 (0.00%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular septal defect
subjects affected / exposed ^[4]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Coordination abnormal
subjects affected / exposed ^[5]	0 / 472 (0.00%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures
subjects affected / exposed ^[6]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Enteritis
subjects affected / exposed ^[7]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed ^[8]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed ^[9]	0 / 472 (0.00%)	1 / 471 (0.21%)	3 / 474 (0.63%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed ^[10]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed ^[11]	3 / 472 (0.64%)	7 / 471 (1.49%)	4 / 474 (0.84%)	4 / 234 (1.71%)
occurrences causally related to treatment / all	0 / 3	0 / 7	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed ^[12]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Measles
subjects affected / exposed ^[13]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed ^[14]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed ^[15]	0 / 472 (0.00%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed ^[16]	1 / 472 (0.21%)	1 / 471 (0.21%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed ^[17]	0 / 472 (0.00%)	1 / 471 (0.21%)	2 / 474 (0.42%)	0 / 234 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.

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

Non-serious adverse events	7vPnC Group 1	13vPnC Group 2	13vPnC Group 3	13vPnC Group 4
Total subjects affected by non serious adverse events
subjects affected / exposed	159 / 472 (33.69%)	166 / 472 (35.17%)	130 / 474 (27.43%)	73 / 234 (31.20%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma
subjects affected / exposed ^[18]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	0	0	0
Congenital, familial and genetic disorders
Heart disease congenital
subjects affected / exposed ^[19]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	0	0	1
Nervous system disorders
Hypersomnia
subjects affected / exposed ^[20]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed ^[21]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Crying
subjects affected / exposed ^[22]	1 / 472 (0.21%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	1	0	0
Injection site erythema
subjects affected / exposed ^[23]	12 / 472 (2.54%)	13 / 471 (2.76%)	10 / 474 (2.11%)	6 / 234 (2.56%)
occurrences all number	13	14	10	6
Injection site swelling
subjects affected / exposed ^[24]	2 / 472 (0.42%)	2 / 471 (0.42%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	2	2	0	1
Pyrexia
subjects affected / exposed ^[25]	5 / 472 (1.06%)	5 / 471 (1.06%)	11 / 474 (2.32%)	3 / 234 (1.28%)
occurrences all number	6	6	11	3
Temperature ≥38°C: Infant series Dose 1
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[26]	3 / 470 (0.64%)	5 / 472 (1.06%)	8 / 472 (1.69%)	3 / 233 (1.29%)
occurrences all number	3	5	8	3
Temperature ≥38°C but ≤39°C : Infant series Dose 1
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.
alternative assessment type: Systematic
subjects affected / exposed ^[27]	3 / 470 (0.64%)	5 / 472 (1.06%)	8 / 472 (1.69%)	3 / 233 (1.29%)
occurrences all number	3	5	8	3
Decreased Appetite:Infant series Dose 1
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[28]	20 / 470 (4.26%)	9 / 472 (1.91%)	22 / 471 (4.67%)	4 / 233 (1.72%)
occurrences all number	20	9	22	4
Irritability: Infant series Dose 1
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[29]	22 / 470 (4.68%)	16 / 472 (3.39%)	58 / 472 (12.29%)	10 / 233 (4.29%)
occurrences all number	22	16	58	10
Increased sleep: Infant series Dose 1
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[30]	12 / 470 (2.55%)	3 / 472 (0.64%)	35 / 471 (7.43%)	2 / 233 (0.86%)
occurrences all number	12	3	35	2
Decreased Sleep: Infant series Dose 1
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[31]	13 / 470 (2.77%)	9 / 472 (1.91%)	27 / 471 (5.73%)	6 / 233 (2.58%)
occurrences all number	13	9	27	6
Temperature ≥ 38°C : Infant series Dose 2
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[32]	4 / 459 (0.87%)	7 / 462 (1.52%)	8 / 459 (1.74%)	3 / 232 (1.29%)
occurrences all number	4	7	8	3
Decreased appetite: Infant series Dose 2
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[33]	12 / 459 (2.61%)	9 / 462 (1.95%)	9 / 459 (1.96%)	1 / 232 (0.43%)
occurrences all number	12	9	9	1
Irritability: Infant series Dose 2
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[34]	25 / 459 (5.45%)	17 / 462 (3.68%)	15 / 460 (3.26%)	2 / 232 (0.86%)
occurrences all number	25	17	15	2
Increased sleep: Infant series Dose 2
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[35]	3 / 459 (0.65%)	0 / 462 (0.00%)	1 / 459 (0.22%)	1 / 232 (0.43%)
occurrences all number	3	0	1	1
Decreased sleep: Infant series Dose 2
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[36]	8 / 459 (1.74%)	8 / 462 (1.73%)	6 / 459 (1.31%)	0 / 232 (0.00%)
occurrences all number	8	8	6	0
Temperature ≥ 38°C : Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[37]	8 / 463 (1.73%)	10 / 467 (2.14%)	8 / 460 (1.74%)	0 / 234 (0.00%)
occurrences all number	8	10	8	0
Temperature ≥38°C but ≤39°C : Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[38]	7 / 463 (1.51%)	9 / 467 (1.93%)	8 / 460 (1.74%)	0 / 234 (0.00%)
occurrences all number	7	9	8	0
Temperature >39°C but ≤40°C: Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[39]	1 / 463 (0.22%)	1 / 467 (0.21%)	1 / 460 (0.22%)	0 / 234 (0.00%)
occurrences all number	1	1	1	0
Decreased appetite: Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[40]	11 / 463 (2.38%)	6 / 467 (1.28%)	11 / 460 (2.39%)	0 / 234 (0.00%)
occurrences all number	11	6	11	0
Irritability: Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed	11 / 472 (2.33%)	10 / 472 (2.12%)	20 / 474 (4.22%)	0 / 234 (0.00%)
occurrences all number	11	10	20	0
Increased sleep: Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[41]	3 / 463 (0.65%)	2 / 467 (0.43%)	2 / 460 (0.43%)	0 / 234 (0.00%)
occurrences all number	3	2	2	0
Decreased sleep: Infant series Dose 3
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[42]	1 / 463 (0.22%)	4 / 467 (0.86%)	6 / 460 (1.30%)	0 / 234 (0.00%)
occurrences all number	1	4	6	0
Temperature ≥ 38°C : after toddler dose
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[43]	14 / 432 (3.24%)	30 / 447 (6.71%)	30 / 446 (6.73%)	14 / 225 (6.22%)
occurrences all number	14	30	30	14
Temperature ≥38°C but ≤39°C : after toddler dose
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[44]	14 / 432 (3.24%)	29 / 447 (6.49%)	28 / 446 (6.28%)	14 / 225 (6.22%)
occurrences all number	14	29	28	14
Temperature >39°C but ≤40°C: after toddler dose
subjects affected / exposed	1 / 472 (0.21%)	4 / 472 (0.85%)	2 / 474 (0.42%)	0 / 234 (0.00%)
occurrences all number	1	4	2	0
Decreased appetite: after toddler dose
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[45]	15 / 433 (3.46%)	11 / 447 (2.46%)	11 / 446 (2.47%)	5 / 225 (2.22%)
occurrences all number	15	11	11	5
Irritability: after toddler dose
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[46]	19 / 432 (4.40%)	15 / 447 (3.36%)	16 / 446 (3.59%)	7 / 225 (3.11%)
occurrences all number	19	15	16	7
Increased sleep: after toddler dose
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[47]	3 / 432 (0.69%)	0 / 447 (0.00%)	0 / 446 (0.00%)	1 / 225 (0.44%)
occurrences all number	3	0	0	1
Decreased sleep: after toddler dose
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[48]	7 / 432 (1.62%)	10 / 447 (2.24%)	7 / 446 (1.57%)	2 / 225 (0.89%)
occurrences all number	7	10	7	2
Temperature ≥38°C but ≤39°C: Infant series dose 2
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.
alternative dictionary used: Systemic events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[49]	4 / 459 (0.87%)	7 / 462 (1.52%)	8 / 459 (1.74%)	3 / 232 (1.29%)
occurrences all number	4	7	8	3
Eye disorders
Dacryoadenitis acquired
subjects affected / exposed ^[50]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	0	0	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed ^[51]	21 / 472 (4.45%)	24 / 471 (5.10%)	15 / 474 (3.16%)	12 / 234 (5.13%)
occurrences all number	22	24	16	14
Dyspepsia
subjects affected / exposed ^[52]	9 / 472 (1.91%)	12 / 471 (2.55%)	5 / 474 (1.05%)	3 / 234 (1.28%)
occurrences all number	9	12	5	3
Mouth ulceration
subjects affected / exposed ^[53]	0 / 472 (0.00%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	0	0	1	0
Enteritis
subjects affected / exposed ^[54]	12 / 472 (2.54%)	13 / 471 (2.76%)	5 / 474 (1.05%)	4 / 234 (1.71%)
occurrences all number	13	13	5	4
Vomiting
subjects affected / exposed ^[55]	0 / 472 (0.00%)	1 / 471 (0.21%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	0	1	1	0
Respiratory, thoracic and mediastinal disorders
Alveolitis allergic
subjects affected / exposed ^[56]	0 / 472 (0.00%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	0	0	1	0
Nasal congestion
subjects affected / exposed ^[57]	0 / 472 (0.00%)	1 / 471 (0.21%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	0	1	1	0
Cough
subjects affected / exposed ^[58]	5 / 472 (1.06%)	4 / 471 (0.85%)	4 / 474 (0.84%)	2 / 234 (0.85%)
occurrences all number	5	4	4	2
Rhinorrhoea
subjects affected / exposed ^[59]	1 / 472 (0.21%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	1	0	1	0
Wheezing
subjects affected / exposed ^[60]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	0	0	1
Skin and subcutaneous tissue disorders
Eczema
subjects affected / exposed ^[61]	2 / 472 (0.42%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	2	0	1	0
Rash
subjects affected / exposed ^[62]	1 / 472 (0.21%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	1	0	0
Erythema
subjects affected / exposed ^[63]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	0	0	0
Urticaria
subjects affected / exposed ^[64]	0 / 472 (0.00%)	1 / 471 (0.21%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	0	1	1	0
Redness (any): Infant series Dose 1
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[65]	19 / 470 (4.04%)	15 / 472 (3.18%)	27 / 472 (5.72%)	8 / 233 (3.43%)
occurrences all number	19	15	27	8
Redness (Mild): Infant Series Dose 1
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[66]	19 / 470 (4.04%)	15 / 472 (3.18%)	26 / 472 (5.51%)	8 / 233 (3.43%)
occurrences all number	19	15	26	8
Redness (Moderate): Infant series Dose 1
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[67]	1 / 470 (0.21%)	0 / 472 (0.00%)	3 / 471 (0.64%)	0 / 233 (0.00%)
occurrences all number	1	0	3	0
Swelling (Any): Infant series Dose 1
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[68]	26 / 470 (5.53%)	19 / 472 (4.03%)	26 / 472 (5.51%)	13 / 233 (5.58%)
occurrences all number	26	19	26	13
Swelling (mild): Infant series Dose 1
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[69]	23 / 470 (4.89%)	16 / 472 (3.39%)	24 / 472 (5.08%)	12 / 233 (5.15%)
occurrences all number	23	16	24	12
Swelling (Moderate): Infant series Dose 1
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[70]	5 / 470 (1.06%)	3 / 472 (0.64%)	5 / 471 (1.06%)	2 / 233 (0.86%)
occurrences all number	5	3	5	2
Tenderness (any): Infant series Dose 1
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[71]	20 / 470 (4.26%)	15 / 472 (3.18%)	36 / 472 (7.63%)	12 / 233 (5.15%)
occurrences all number	20	15	36	12
Tenderness (Present): Infant series Dose 1
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[72]	18 / 470 (3.83%)	14 / 472 (2.97%)	36 / 472 (7.63%)	9 / 233 (3.86%)
occurrences all number	18	14	36	9
Tenderness (Significant): Infant series Dose 1
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[73]	2 / 470 (0.43%)	1 / 472 (0.21%)	0 / 472 (0.00%)	3 / 233 (1.29%)
occurrences all number	2	1	0	3
Redness (any): Infant series Dose 2
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.
alternative dictionary used: Local Reactions 0.0
subjects affected / exposed ^[74]	13 / 459 (2.83%)	10 / 462 (2.16%)	20 / 460 (4.35%)	4 / 232 (1.72%)
occurrences all number	13	10	20	4
Redness (Moderate): Infant series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[75]	2 / 459 (0.44%)	3 / 462 (0.65%)	3 / 460 (0.65%)	0 / 232 (0.00%)
occurrences all number	2	3	3	0
Redness (Mild): Infant Series Dose 2
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative assessment type: Systematic
subjects affected / exposed ^[76]	12 / 459 (2.61%)	8 / 462 (1.73%)	18 / 460 (3.91%)	4 / 232 (1.72%)
occurrences all number	12	8	18	4
Swelling (Any): Infant series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[77]	16 / 459 (3.49%)	11 / 462 (2.38%)	19 / 459 (4.14%)	4 / 232 (1.72%)
occurrences all number	16	11	19	4
Swelling (mild): Infant series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[78]	15 / 459 (3.27%)	10 / 462 (2.16%)	17 / 459 (3.70%)	4 / 232 (1.72%)
occurrences all number	15	10	17	4
Swelling (Moderate): Infant series Dose 2
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[79]	3 / 459 (0.65%)	2 / 462 (0.43%)	2 / 459 (0.44%)	1 / 232 (0.43%)
occurrences all number	3	2	2	1
Tenderness (any): Infant series Dose 2
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[80]	13 / 459 (2.83%)	11 / 462 (2.38%)	28 / 460 (6.09%)	6 / 232 (2.59%)
occurrences all number	13	11	28	6
Tenderness (Present): Infant series Dose 2
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative assessment type: Systematic
subjects affected / exposed ^[81]	12 / 459 (2.61%)	9 / 462 (1.95%)	28 / 459 (6.10%)	6 / 232 (2.59%)
occurrences all number	12	9	28	6
Tenderness (Significant): Infant series Dose 2
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[82]	1 / 459 (0.22%)	2 / 462 (0.43%)	0 / 460 (0.00%)	0 / 232 (0.00%)
occurrences all number	1	2	0	0
Redness (any): Infant series Dose 3
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[83]	9 / 463 (1.94%)	10 / 467 (2.14%)	8 / 460 (1.74%)	0 / 234 (0.00%)
occurrences all number	9	10	8	0
Redness (Mild): Infant Series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[84]	8 / 463 (1.73%)	10 / 467 (2.14%)	5 / 460 (1.09%)	0 / 234 (0.00%)
occurrences all number	8	10	5	0
Redness (Moderate): Infant series Dose 3
Additional description: Subjects affected and occurrences for LRsand SEs is same as data collected through e- diaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[85]	1 / 463 (0.22%)	1 / 467 (0.21%)	4 / 460 (0.87%)	0 / 234 (0.00%)
occurrences all number	1	1	4	0
Swelling (Any): Infant series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[86]	9 / 463 (1.94%)	9 / 467 (1.93%)	11 / 460 (2.39%)	0 / 234 (0.00%)
occurrences all number	9	9	11	0
Swelling (mild): Infant series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[87]	9 / 463 (1.94%)	9 / 467 (1.93%)	10 / 460 (2.17%)	0 / 234 (0.00%)
occurrences all number	9	9	10	0
Swelling (Moderate): Infant series Dose 3
Additional description: 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.
alternative assessment type: Systematic
subjects affected / exposed ^[88]	0 / 463 (0.00%)	1 / 467 (0.21%)	3 / 460 (0.65%)	0 / 234 (0.00%)
occurrences all number	0	1	3	0
Tenderness (any): Infant series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[89]	23 / 463 (4.97%)	16 / 467 (3.43%)	16 / 460 (3.48%)	0 / 234 (0.00%)
occurrences all number	23	16	16	0
Tenderness (Present): Infant series Dose 3
Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[90]	20 / 463 (4.32%)	15 / 467 (3.21%)	15 / 460 (3.26%)	0 / 234 (0.00%)
occurrences all number	20	15	15	0
Tenderness (Significant): Infant series Dose 3
Additional description: 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.
alternative assessment type: Systematic
subjects affected / exposed ^[91]	3 / 463 (0.65%)	1 / 467 (0.21%)	1 / 460 (0.22%)	0 / 234 (0.00%)
occurrences all number	3	1	1	0
Redness (any): After toddler dose
Additional description: 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.
alternative assessment type: Systematic
subjects affected / exposed ^[92]	9 / 432 (2.08%)	15 / 447 (3.36%)	16 / 446 (3.59%)	4 / 225 (1.78%)
occurrences all number	9	15	16	4
Redness (Mild): After toddler dose
Additional description: 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.
alternative assessment type: Systematic
subjects affected / exposed ^[93]	6 / 432 (1.39%)	11 / 447 (2.46%)	11 / 446 (2.47%)	1 / 225 (0.44%)
occurrences all number	6	11	11	1
Redness (Moderate): After toddler dose
Additional description: 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.
alternative assessment type: Systematic
subjects affected / exposed ^[94]	6 / 432 (1.39%)	7 / 447 (1.57%)	6 / 446 (1.35%)	3 / 225 (1.33%)
occurrences all number	6	7	6	3
Swelling (Any): After toddler dose
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
subjects affected / exposed ^[95]	15 / 432 (3.47%)	16 / 447 (3.58%)	16 / 446 (3.59%)	7 / 225 (3.11%)
occurrences all number	15	16	16	7
Swelling (mild):After toddler dose
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative assessment type: Systematic
subjects affected / exposed ^[96]	10 / 432 (2.31%)	12 / 447 (2.68%)	12 / 446 (2.69%)	4 / 225 (1.78%)
occurrences all number	10	12	12	4
Swelling (Moderate): After toddler dose
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative assessment type: Systematic
subjects affected / exposed ^[97]	7 / 432 (1.62%)	6 / 447 (1.34%)	6 / 446 (1.35%)	4 / 225 (1.78%)
occurrences all number	7	6	6	4
Swelling (Severe): After toddler dose
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative assessment type: Systematic
subjects affected / exposed ^[98]	0 / 432 (0.00%)	0 / 447 (0.00%)	0 / 446 (0.00%)	1 / 225 (0.44%)
occurrences all number	0	0	0	1
Tenderness (any): After toddler dose
Additional description: Additional description: Subjects affected and occurrences for LRs and SEs is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative assessment type: Systematic
subjects affected / exposed ^[99]	28 / 432 (6.48%)	22 / 447 (4.92%)	24 / 446 (5.38%)	12 / 225 (5.33%)
occurrences all number	28	22	24	12
Tenderness (Present): After toddler dose
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[100]	28 / 432 (6.48%)	20 / 447 (4.47%)	21 / 446 (4.71%)	12 / 225 (5.33%)
occurrences all number	28	20	21	12
Tenderness (Significant): After toddler dose
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.
alternative assessment type: Systematic
subjects affected / exposed ^[101]	0 / 432 (0.00%)	2 / 447 (0.45%)	3 / 446 (0.67%)	0 / 225 (0.00%)
occurrences all number	0	2	3	0
Redness (Severe): After toddler dose
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.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[102]	0 / 432 (0.00%)	0 / 447 (0.00%)	0 / 446 (0.00%)	1 / 225 (0.44%)
occurrences all number	0	0	0	1
Psychiatric disorders
Irritability
subjects affected / exposed ^[103]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	0	0	1
Infections and infestations
Bronchitis
subjects affected / exposed ^[104]	10 / 472 (2.12%)	11 / 471 (2.34%)	6 / 474 (1.27%)	3 / 234 (1.28%)
occurrences all number	10	11	6	3
Bronchopneumonia
subjects affected / exposed ^[105]	7 / 472 (1.48%)	7 / 471 (1.49%)	7 / 474 (1.48%)	0 / 234 (0.00%)
occurrences all number	7	7	7	0
Gastroenteritis
subjects affected / exposed ^[106]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	0	0	0	0
Gingivitis
subjects affected / exposed ^[107]	0 / 472 (0.00%)	0 / 471 (0.00%)	1 / 474 (0.21%)	0 / 234 (0.00%)
occurrences all number	0	0	1	0
Laryngitis
subjects affected / exposed ^[108]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	0	1	0	0
Nasopharyngitis
subjects affected / exposed ^[109]	97 / 472 (20.55%)	91 / 471 (19.32%)	68 / 474 (14.35%)	34 / 234 (14.53%)
occurrences all number	122	123	91	43
Oral candidiasis
subjects affected / exposed ^[110]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	0	0	0
Oral fungal infection
subjects affected / exposed ^[111]	1 / 472 (0.21%)	0 / 471 (0.00%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	1	0	0	0
Pneumonia
subjects affected / exposed ^[112]	1 / 472 (0.21%)	3 / 471 (0.64%)	2 / 474 (0.42%)	1 / 234 (0.43%)
occurrences all number	1	3	2	1
Rhinitis
subjects affected / exposed ^[113]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	0	1	0	0
Tonsillitis
subjects affected / exposed ^[114]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	1	0	1
Upper respiratory tract infection
subjects affected / exposed ^[115]	38 / 472 (8.05%)	34 / 471 (7.22%)	31 / 474 (6.54%)	19 / 234 (8.12%)
occurrences all number	43	38	35	20
Tracheitis
subjects affected / exposed ^[116]	2 / 472 (0.42%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	2	1	0	0
Viral skin infection
subjects affected / exposed ^[117]	0 / 472 (0.00%)	0 / 471 (0.00%)	0 / 474 (0.00%)	1 / 234 (0.43%)
occurrences all number	0	0	0	1
Metabolism and nutrition disorders
Calcium deficiency
subjects affected / exposed ^[118]	0 / 472 (0.00%)	1 / 471 (0.21%)	0 / 474 (0.00%)	0 / 234 (0.00%)
occurrences all number	0	1	0	0

Notes
[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 evaluable for adverse event.
[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 evaluable for adverse event.
[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 evaluable for adverse event.
[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 evaluable for adverse event.
[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 evaluable for adverse event.
[23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[40] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[41] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[42] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[43] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[44] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[45] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[46] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[47] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[48] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[49] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all 7 days.
[50] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[51] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[52] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects evaluable for adverse event.
[53] - 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 evaluable for adverse event.
[54] - 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 evaluable for adverse event.
[55] - 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 evaluable for adverse event.
[56] - 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 evaluable for adverse event.
[57] - 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 evaluable for adverse event.
[58] - 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 evaluable for adverse event.
[59] - 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 evaluable for adverse event.
[60] - 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 evaluable for adverse event.
[61] - 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 evaluable for adverse event.
[62] - 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 evaluable for adverse event.
[63] - 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 evaluable for adverse event.
[64] - 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 evaluable for adverse event.
[65] - 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 7 days.
[66] - 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 7 days.
[67] - 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 7 days.
[68] - 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 7 days.
[69] - 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 7 days.
[70] - 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 7 days.
[71] - 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 7 days.
[72] - 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 7 days.
[73] - 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 7 days.
[74] - 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 7 days.
[75] - 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 7 days.
[76] - 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 7 days.
[77] - 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 7 days.
[78] - 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 7 days.
[79] - 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 7 days.
[80] - 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 7 days.
[81] - 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 7 days.
[82] - 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 7 days.
[83] - 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 7 days.
[84] - 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 7 days.
[85] - 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 7 days.
[86] - 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 7 days.
[87] - 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 7 days.
[88] - 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 7 days.
[89] - 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 7 days.
[90] - 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 7 days.
[91] - 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 7 days.
[92] - 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 7 days.
[93] - 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 7 days.
[94] - 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 7 days.
[95] - 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 7 days.
[96] - 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 7 days.
[97] - 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 7 days.
[98] - 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 7 days.
[99] - 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 7 days.
[100] - 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 7 days.
[101] - 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 7 days.
[102] - 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 7 days.
[103] - 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 evaluable for adverse event.
[104] - 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 evaluable for adverse event.
[105] - 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 evaluable for adverse event.
[106] - 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 evaluable for adverse event.
[107] - 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 evaluable for adverse event.
[108] - 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 evaluable for adverse event.
[109] - 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 evaluable for adverse event.
[110] - 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 evaluable for adverse event.
[111] - 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 evaluable for adverse event.
[112] - 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 evaluable for adverse event.
[113] - 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 evaluable for adverse event.
[114] - 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 evaluable for adverse event.
[115] - 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 evaluable for adverse event.
[116] - 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 evaluable for adverse event.
[117] - 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 evaluable for adverse event.
[118] - 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 evaluable for adverse event.

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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, Active-Controlled Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) Compared with a 7-Valent Pneumococcal Conjugate Vaccine (7vPnC) in Healthy Infants in China.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving a Pneumococcal Immunoglobin G(IgG) Antibody Concentration Greater Than or Equal to (≥)0.35 microgram per milliliter (µg/mL) 1 Month After the Infant Series, 13vPnC Group 2 versus (vs) 7vPnC Group 1

Primary: Percentage of Subjects Achieving a Pneumococcal Immunoglobin G(IgG) Antibody Concentration Greater Than or Equal to (≥)0.35 microgram per milliliter (µg/mL) 1 Month After the Infant Series, 13vPnC Group 2 versus (vs) 7vPnC Group 1

Primary: Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 3 vs 7vPnC Group 1

Primary: Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 3 vs 7vPnC Group 1

Primary: Geometric Mean Concentration (GMC) for serotype-specific pneumococcal immunoglobulin G (IgG) antibody 1 month after the infant series, 13vPnC Group 2 vs 7vPnC Group 1

Primary: Geometric Mean Concentration (GMC) for serotype-specific pneumococcal immunoglobulin G (IgG) antibody 1 month after the infant series, 13vPnC Group 2 vs 7vPnC Group 1

Primary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, Group 3 vs 7vPnC Group 1

Primary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, Group 3 vs 7vPnC Group 1

Primary: Percentage of subjects reporting local reactions within 7 days after dose 1 in infant series

Primary: Percentage of subjects reporting local reactions within 7 days after dose 1 in infant series

Primary: Percentage of subjects reporting local reactions within 7 days after dose 2 in infant series

Primary: Percentage of subjects reporting local reactions within 7 days after dose 2 in infant series

Primary: Percentage of subjects reporting local reactions within 7 days after dose 3 in infant series

Primary: Percentage of subjects reporting local reactions within 7 days after dose 3 in infant series

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 1 in infant series

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 1 in infant series

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 2 in infant series

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 2 in infant series

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 3 in infant series

Primary: Percentage of subjects reporting systemic events and antipyretic medication use within 7 days after dose 3 in infant series

Primary: Percentage of subjects reporting local reactions within 7 days after toddler dose

Primary: Percentage of subjects reporting local reactions within 7 days after toddler dose

Primary: Percentage of Subjects reporting systemic events and antipyretic medication use within 7 days after toddler dose

Primary: Percentage of Subjects reporting systemic events and antipyretic medication use within 7 days after toddler dose

Secondary: Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal IgG antibody concentration ≥0.35 µg/mL 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the infant series, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal Opsonophagocytic Activity (OPA) antibody titer ≥ Lower Limit of Quantitation (LLOQ) in infant series, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal Opsonophagocytic Activity (OPA) antibody titer ≥ Lower Limit of Quantitation (LLOQ) in infant series, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ in infant series, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Serotype-specific OPA Geometric Mean Titer (GMT) 1 month after the infant series 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Serotype-specific OPA Geometric Mean Titer (GMT) 1 month after the infant series 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the infant series 13vPnC Group 4 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: GMC for serotype-specific pneumococcal IgG antibody 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Percentage of Subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Percentage of subjects achieving a pneumococcal OPA antibody titer ≥ LLOQ after toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 2 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 3 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Secondary: Serotype-specific OPA GMT 1 month after the toddler dose, 13vPnC Group 4 vs 7vPnC Group 1

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Randomized, Active-Controlled Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) Compared with a 7-Valent Pneumococcal Conjugate Vaccine (7vPnC) in Healthy Infants in China.