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Clinical Trial Results:
A Phase 3, Randomised, Active-Controlled, Double-Blind Trial Evaluating the Safety, Tolerability and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Paediatric Vaccinations in India

Summary
EudraCT number	2008-003687-20
Trial protocol	Outside EU/EEA
Global end of trial date	13 Oct 2009

Results information
Results version number	v1(current)
This version publication date	29 Jun 2016
First version publication date	05 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

6096A1-011

ISRCTN number

US NCT number

NCT00452790

WHO universal trial number (UTN)

Other trial identifiers

Alias: B1851002

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.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

14 May 2010

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Oct 2009

Was the trial ended prematurely?

Main objective of the trial

- To assess the pneumococcal immune responses induced by 13-Valent Pneumococcal Conjugate Vaccine (13vPnC) relative to the pneumococcal immune responses induced by 7-Valent Pneumococcal Conjugate Vaccine (7vPnC) when measured 1 month after the infant series. - To assess the immune responses induced by diphtheria, tetanus, whole cell pertussis; Haemphilus influenzae (H influenzae) type b (Hib); and hepatitis B vaccine (DTP-Hib-HBV) given with 13vPnC relative to the immune responses induced by DTP-Hib-HBV given with 7vPnC when measured 1 month after the infant series. The following antigens in DTP-Hib-HBV will be assessed: pertussis antigens (pertussis toxoid [PT], filamentous haemagglutinin [FHA], and pertactin [PRN]).

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

26 Jul 2007

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

India: 709

Worldwide total number of subjects

709

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)

709

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

708 subjects were enrolled and 709 were randomized into the study. One infant in the 13vPnC group was randomly assigned twice because of technical difficulties with the first random assignment. Though this infant participated in the study only once, both random assignments were included in the 354 subjects in the 13vPnC group.

Period 1 title

Infant Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC: Infant series

Arm description

Subjects received 1 single dose of 13vPnC, at 6, 10 and 14 weeks of age co-administered with a commercially available combination vaccine containing diphtheria, tetanus, whole cell pertussis; H influenzae type b and hepatitis B vaccine (DTP-Hib-HBV); and a commercially available oral polio vaccine (OPV).

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 milliliter (mL) dose of 13vPnC at 6, 10 and 14 weeks of age.

Investigational medicinal product name

DTP-Hib-HBV

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received DTP-Hib-HBV dose at 6, 10 and 14 weeks of age.

Investigational medicinal product name

OPV

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Subjects received OPV dose at 6, 10 and 14 weeks of age.

7vPnC: Infant Series

Arm description

Subjects received 1 single dose of 7vPnC at 6, 10 and 14 weeks of age co-administered with a commercially available combination vaccine DTP-Hib-HBV and a commercially available OPV.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 7vPnC at 6, 10 and 14 weeks of age.

Investigational medicinal product name

DTP-Hib-HBV

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received DTP-Hib-HBV dose at 6, 10 and 14 weeks of age.

Investigational medicinal product name

OPV

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral liquid

Routes of administration

Oral use

Dosage and administration details

Subjects received OPV dose at 6, 10 and 14 weeks of age.

Number of subjects in period 1	13vPnC: Infant series	7vPnC: Infant Series
Started	354	355
Vaccinated Dose 1	353	353
Vaccinated Dose 2	300	300
Vaccinated Dose 3	221	218
Completed	219	214
Not completed	135	141
Clinical hold - consent withdrawn	118	123
Failed to return	4	1
Adverse Event	1	2
Parent/legal guardian request	8	6
'Protocol Violation '	1	3
Other reasons	1	2
Lost to follow-up	2	2
'Death '	-	1
Investigator request	-	1

Period 2 title

After Infant Series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC: After Infant series

Arm description

Subjects who received 1 single dose of 13vPnC at 6, 10 and 14 weeks of age, co-administered with a commercially available combination vaccine containing DTP-Hib-HBV and a commercially available OPV in the infant seies.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

7vPnC: After Infant series

Arm description

Subjects who received 1 single dose of 7vPnC at 6, 10 and 14 weeks of age co-administered with a commercially available combination vaccine containing DTP-Hib-HBV and a commercially available OPV in the infant series.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	13vPnC: After Infant series	7vPnC: After Infant series
Started	219	214
Completed	198	200
Not completed	21	14
Adverse Event	4	1
Failed to return	1	-
Parent/legal guardian request	1	3
Other reasons	1	-
Lost to follow-up	4	-
Investigator request	10	10

Period 3 title

Toddler Dose

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC: Toddler Dose

Arm description

Subjects received 1 single dose of 13vPnC administered at 12 months of age.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 13vPnC at 12 months of age.

7vPnC: Toddler Dose

Arm description

Subjects received 1 single dose of 7vPnC administered at 12 months of age.

Arm type

Active comparator

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of 7vPnC at 12 months of age.

Number of subjects in period 3	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Started	198	200
Completed	198	198
Not completed	0	2
'Parent/legal guardian request '	-	1
Failed to return	-	1

Baseline characteristics

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Reporting group title

13vPnC: Infant series

Reporting group description

Reporting group title

7vPnC: Infant Series

Reporting group description

Subjects received 1 single dose of 7vPnC at 6, 10 and 14 weeks of age co-administered with a commercially available combination vaccine DTP-Hib-HBV and a commercially available OPV.

Reporting group values	13vPnC: Infant series	7vPnC: Infant Series	Total
Number of subjects	354	355	709
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	1.6 ( 0.3 )	1.6 ( 0.2 )	-
Gender categorical
Units: Subjects
Female	169	169	338
Male	184	186	370
Unknown	1	0	1
Age continuous
Units: weeks
arithmetic mean (standard deviation)	7.1 ( 1.1 )	7.2 ( 1.1 )	-

End points

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Reporting group title

13vPnC: Infant series

Reporting group description

Reporting group title

7vPnC: Infant Series

Reporting group description

Subjects received 1 single dose of 7vPnC at 6, 10 and 14 weeks of age co-administered with a commercially available combination vaccine DTP-Hib-HBV and a commercially available OPV.

Reporting group title

13vPnC: After Infant series

Reporting group description

Reporting group title

7vPnC: After Infant series

Reporting group description

Reporting group title

13vPnC: Toddler Dose

Reporting group description

Subjects received 1 single dose of 13vPnC administered at 12 months of age.

Reporting group title

7vPnC: Toddler Dose

Reporting group description

Subjects received 1 single dose of 7vPnC administered at 12 months of age.

Primary: Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to (>=) 0.35 Micrograms per Milliliter (mcg/mL), 1 Month After the Infant Series.

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End point title

Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to (>=) 0.35 Micrograms per Milliliter (mcg/mL), 1 Month After the Infant Series. ^[1]

End point description

Percentage of subjects achieving a predefined antibody level of >=0.35 mcg/mL along with the corresponding O'Brien-Fleming-adjusted, exact, 2-sided 95 percent (%) confidence interval (CI) for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F and 19 A) are presented. Evaluable immunogenicity population: had treatments as randomized at all 3 doses, blood drawn within specified timeframes, had at least 1 valid and determinate assay result for the proposed analysis, and no major protocol violations. n=number of subjects with determinate IgG antibody concentration for the specified serotype.

End point type

Primary

End point timeframe

1 month after the infant series (18 weeks of age)

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

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	206	196
Units: Percentage of subjects
number (confidence interval 95.2%)
Common serotypes - serotype 4 (n= 203, 192)	97 (93.6 to 98.9)	97.9 (94.7 to 99.4)
Common serotypes - serotype 6B (n= 196,194)	84.7 (78.8 to 89.5)	87.1 (81.5 to 91.5)
Common serotypes - serotype 9V (n= 204,195)	92.6 (88.1 to 95.8)	94.4 (90.1 to 97.2)
Common serotypes - serotype 14 (n= 185,186)	91.4 (86.3 to 95)	93.5 (89 to 96.6)
Common serotypes - serotype 18C (n= 204,188)	95.1 (91.1 to 97.6)	93.1 (88.4 to 96.3)
Common serotypes - serotype 19F (n= 200,188)	95 (91 to 97.6)	94.7 (90.4 to 97.4)
Common serotypes - serotype 23F (n= 202,186)	90.1 (85.1 to 93.9)	89.2 (83.8 to 93.3)
Additional serotypes - serotype 1 (n= 206,195)	96.6 (93.1 to 98.6)	0.5 (0 to 2.8)
Additional serotypes - serotype 3 (n= 201,187)	87.6 (82.1 to 91.8)	2.1 (0.6 to 5.4)
Additional serotypes - serotype 5 (n= 201,185)	85.1 (79.3 to 89.7)	24.3 (18.3 to 31.2)
Additional serotypes - serotype 6A (n= 200,191)	90 (84.9 to 93.8)	36.1 (29.3 to 43.4)
Additional serotypes - serotype 7F (n= 203,192)	98 (95 to 99.5)	2.6 (0.8 to 6)
Additional serotypes - serotype 19 A (n= 204,190)	99.5 (97.3 to 100)	84.7 (78.8 to 89.6)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving a Predefined Antibody Level for Concomitant Vaccine Pertussis Antigens (Pertussis Toxoid [PT], Filamentous Hemagglutinin [FHA], Pertactin [PRN]), 1 Month After the Infant Series.

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End point title

Percentage of Subjects Achieving a Predefined Antibody Level for Concomitant Vaccine Pertussis Antigens (Pertussis Toxoid [PT], Filamentous Hemagglutinin [FHA], Pertactin [PRN]), 1 Month After the Infant Series. ^[2]

End point description

Percentage of subjects achieving a predefined antibody level (measured in enzyme-linked immunosorbent assay [ELISA] units per mL [EU/mL]) along with the corresponding O'Brien-Fleming-adjusted, exact, 2-sided 95% CI for concomitant antigens pertussis (PT, FHA and PRN) are presented. Evaluable immunogenicity population: had treatments as randomized at all 3 doses, blood drawn within specified timeframes, had at least 1 valid and determinate assay result for the proposed analysis, and no major protocol violations.

End point type

Primary

End point timeframe

1 month after the infant series (18 weeks of age)

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

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	206	196
Units: Percentage of subjects
number (confidence interval 95.2%)
PT >=0.975 EU/mL	100 (98.2 to 100)	100 (98.1 to 100)
FHA >=3.91 EU/mL	100 (98.2 to 100)	100 (98.1 to 100)
PRN >=6 EU/mL	92.7 (88.2 to 95.9)	95.9 (92.1 to 98.2)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to 0.35 Mcg/mL, 1 Month After the Toddler Dose.

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End point title

Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to 0.35 Mcg/mL, 1 Month After the Toddler Dose.

End point description

Percentage of subjects achieving a predefined antibody level of >=0.35 mcg/mL along with the corresponding exact, 2-sided 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F and 19 A) are presented. Evaluable immunogenicity population: had treatments as randomized at all 4 doses, blood drawn within specified timeframes, had at least 1 valid and determinate assay result for the proposed analysis, and no major protocol violations. n=number of subjects with determinate IgG antibody concentration for the specified serotype.

End point type

Secondary

End point timeframe

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

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	193	196
Units: Percentage of subjects
number (confidence interval 95%)
Common serotypes - serotype 4 (n= 193, 196)	100 (98.1 to 100)	100 (98.1 to 100)
Common serotypes - serotype 6B (n= 192,195)	100 (98.1 to 100)	99.5 (97.2 to 100)
Common serotypes - serotype 9V (n= 193,196)	99.5 (97.1 to 100)	99.5 (97.2 to 100)
Common serotypes - serotype 14 (n= 193,196)	99.5 (97.1 to 100)	99.5 (97.2 to 100)
Common serotypes - serotype 18C (n= 193,196)	99.5 (97.1 to 100)	99 (96.4 to 99.9)
Common serotypes - serotype 19F (n= 193,196)	97.9 (94.8 to 99.4)	98 (94.9 to 99.4)
Common serotypes - serotype 23F (n= 193,196)	98.4 (95.5 to 99.7)	99.5 (97.2 to 100)
Additional serotypes - serotype 1 (n= 193,195)	98.4 (95.5 to 99.7)	3.1 (1.1 to 6.6)
Additional serotypes - serotype 3 (n= 193,194)	90.2 (85.1 to 94)	12.9 (8.5 to 18.4)
Additional serotypes - serotype 5 (n= 192,183)	100 (98.1 to 100)	74.3 (67.4 to 80.5)
Additional serotypes - serotype 6A (n= 193,194)	100 (98.1 to 100)	92.8 (88.2 to 96)
Additional serotypes - serotype 7F (n= 193,194)	99 (96.3 to 99)	9.8 (6 to 14.9)
Additional serotypes - serotype 19 A (n= 193,194)	100 (98.1 to 100)	98.5 (95.5 to 99.7)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody, 1 Month After the 3-Dose Infant Series

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End point title

Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody, 1 Month After the 3-Dose Infant Series

End point description

Antibody GMC as measured in mcg/mL for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC (13vPnC) and corresponding O'Brien-Fleming-adjusted, 2-sided 95% CIs were calculated. Evaluable immunogenicity population: had treatments as randomized at all 3 doses, blood drawn within specified timeframes, had at least 1 valid and determinate assay result for the proposed analysis, and no major protocol violations. n=number of subjects with determinate IgG antibody concentration for the specified serotype.

End point type

Other pre-specified

End point timeframe

1 month after the 3-dose infant series (18 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	206	196
Units: mcg/mL
geometric mean (confidence interval 95.2%)
Common serotypes - serotype 4 (n= 203,192)	2.19 (1.95 to 2.46)	2.58 (2.26 to 2.95)
Common serotypes - serotype 6B (n= 196,194)	1.45 (1.2 to 1.75)	1.56 (1.28 to 1.89)
Common serotypes - serotype 9V (n= 204,195)	1.34 (1.19 to 1.5)	1.46 (1.28 to 1.65)
Common serotypes - serotype 14 (n= 185,186)	2.84 (2.35 to 3.43)	2.39 (1.98 to 2.9)
Common serotypes - serotype 18C (n= 204,188)	1.61 (1.42 to 1.82)	1.7 (1.47 to 1.96)
Common serotypes - serotype 19F (n= 200,188)	2.25 (1.97 to 2.56)	2.47 (2.11 to 2.89)
Common serotypes - serotype 23F (n= 202,186)	1.38 (1.18 to 1.6)	1.46 (1.25 to 1.7)
Additional serotypes - serotype 1 (n= 206,195)	1.95 (1.72 to 2.22)	0.03 (0.03 to 0.04)
Additional serotypes - serotype 3 (n= 201,187)	0.8 (0.72 to 0.9)	0.05 (0.05 to 0.06)
Additional serotypes - serotype 5 (n= 201,185)	0.93 (0.82 to 1.06)	0.2 (0.18 to 0.23)
Additional serotypes - serotype 6A (n= 200,191)	1.44 (1.25 to 1.66)	0.28 (0.25 to 0.31)
Additional serotypes - serotype 7F (n= 203,192)	2.27 (2.05 to 2.33)	0.06 (0.05 to 0.06)
Additional serotypes - serotype 19A (n= 204,190)	2.76 (2.46 to 3.1)	0.74 (0.66 to 0.82)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal IgG Antibody, 1 Month After the Toddler Dose

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End point title

Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal IgG Antibody, 1 Month After the Toddler Dose

End point description

Antibody GMC as measured in mcg/mL for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. GMC (13vPnC) and corresponding 2-sided 95% CIs were presented. Evaluable immunogenicity population: had treatments as randomized at all 4 doses, blood drawn within specified timeframes, had at least 1 valid and determinate assay result for the proposed analysis, and no major protocol violations. n=number of subjects with determinate IgG antibody concentration for the specified serotype.

End point type

Other pre-specified

End point timeframe

1 month after toddler dose (13 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	193	196
Units: mcg/mL
geometric mean (confidence interval 95%)
Common serotypes - serotype 4 (n= 193, 196)	5.33 (4.69 to 6.04)	5.85 (5.13 to 6.68)
Common serotypes - serotype 6B (n= 192, 195)	12.24 (10.6 to 14.13)	11.6 (9.95 to 13.53)
Common serotypes - serotype 9V (n= 193,196)	3.01 (2.68 to 3.37)	3.33 (2.96 to 3.75)
Common serotypes - serotype 14 (n= 193,196)	10.59 (9.21 to 12.18)	10.95 (9.41 to 12.74)
Common serotypes - serotype 18C (n= 193,196)	2.63 (2.33 to 2.97)	2.98 (2.65 to 3.34)
Common serotypes - serotype 19F (n= 193,196)	8.38 (7.11 to 9.87)	5.65 (4.84 to 6.58)
Common serotypes - serotype 23F (n= 193,196)	4.27 (3.66 to 4.98)	5.31 (4.66 to 6.04)
Additional serotypes - serotype 1 (n= 193,195)	5.1 (4.39 to 5.92)	0.04 (0.04 to 0.05)
Additional serotypes - serotype 3 (n= 193,194)	0.91 (0.81 to 1.03)	0.09 (0.08 to 0.11)
Additional serotypes - serotype 5 (n= 192,183)	3.58 (3.2 to 4)	0.64 (0.55 to 0.75)
Additional serotypes - serotype 6A (n= 193,194)	8.13 (7.11 to 9.28)	1.87 (1.62 to 2.17)
Additional serotypes - serotype 7F (n= 193,194)	4.81 (4.27 to 5.42)	0.06 (0.05 to 0.08)
Additional serotypes - serotype 19A (n= 193,194)	14.12 (12.45 to 16.01)	3.56 (3.14 to 4.05)

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 1 (6 Weeks of Age)

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End point title

Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 1 (6 Weeks of Age)

End point description

Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeter [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe ( greater than [>] 7.0 cm). Subjects may be represented in more than 1 category. Safety population: all subjects who received dose 1 of the infant series vaccination (6 weeks of age). n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the dose 1 of the infant series (6 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	353	353
Units: Percentage of subjects
number (not applicable)
Tenderness: Any (n= 347,347)	62.5	59.7
Tenderness: Significant (n= 341,343)	42.2	40.5
Induration: Any (n= 339,342)	21.5	22.5
Induration: Mild (n= 338,340)	19.2	19.1
Induration: Moderate (n= 331,338)	4.8	5.6
Induration: Severe (n= 329,336)	0	0
Erythema: Any (n= 333,339)	12.6	13.3
Erythema: Mild (n= 333,338)	11.4	11.8
Erythema: Moderate (n= 330,337)	1.5	1.8
Erythema: Severe (n= 329,336)	0	0
Any of the above (n= 349,348)	66.8	65.2

Tenderness-any

Statistical analysis description

Difference in incidence rates of tenderness-any within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.483

Method

Fisher exact

Confidence interval

Tenderness-significant

Statistical analysis description

Difference in incidence rates of tenderness-significant within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.698

Method

Fisher exact

Confidence interval

Induration-any

Statistical analysis description

Difference in incidence rates of induration-any within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.782

Method

Fisher exact

Confidence interval

Induration-mild

Statistical analysis description

Difference in incidence rates of induration-mild within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Induration-moderate

Statistical analysis description

Difference in incidence rates of induration-moderate within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.729

Method

Fisher exact

Confidence interval

Induration-severe

Statistical analysis description

Difference in incidence rates of Induration-Severe within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[3]

Method

Fisher exact

Confidence interval

Notes
[3] - Here, "99999" in the p-value signifies not applicable, since no severe induration in both groups.

Erythema-any

Statistical analysis description

Difference in incidence rates of Erythema-Any within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.819

Method

Fisher exact

Confidence interval

Erythema-mild

Statistical analysis description

Difference in incidence rates of erythema-mild within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.904

Method

Fisher exact

Confidence interval

Erythema-moderate

Statistical analysis description

Difference in incidence rates of Erythema-Moderate within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Erythema-severe

Statistical analysis description

Difference in incidence rates of erythema-severe within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[4]

Method

Fisher exact

Confidence interval

Notes
[4] - Here, "99999" in the p-value signifies not applicable, since no severe erythema in both groups".

Any local reaction

Statistical analysis description

Difference in incidence rates of any local reaction (tenderness, induration and erythema) within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.69

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 2 (10 Weeks of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 2 (10 Weeks of Age)

End point description

Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 cm to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category. Safety population: all subjects who received the first 2 doses of the infant series vaccination (10 weeks of age). n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the dose 2 of the infant series (10 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	300	300
Units: Percentage of subjects
number (not applicable)
Tenderness: Any (n= 284,282)	44.4	44
Tenderness: Significant (n= 278,279)	26.6	28
Induration: Any (n= 281,278)	20.6	18.7
Induration: Mild (n= 281,277)	16.7	16.2
Induration: Moderate (n= 273,272)	5.1	4
Induration: Severe (n= 273,271)	0	0
Erythema: Any (n= 275,280)	13.8	17.9
Erythema: Mild (n= 275,279)	13.1	15.8
Erythema: Moderate (n= 273,273)	1.5	2.9
Erythema: Severe (n= 273,271)	0	0
Any of the above (n= 285,286)	51.6	53.1

Tenderness-any

Statistical analysis description

Difference in incidence rates of tenderness-any within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.933

Method

Fisher exact

Confidence interval

Tenderness-significant

Statistical analysis description

Difference in incidence rates of tenderness-significant within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.776

Method

Fisher exact

Confidence interval

Induration-any

Statistical analysis description

Difference in incidence rates of induration-any within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.596

Method

Fisher exact

Confidence interval

Induration-mild

Statistical analysis description

Difference in incidence rates of induration-mild within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.909

Method

Fisher exact

Confidence interval

Induration-moderate

Statistical analysis description

Difference in incidence rates of induration-moderate within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.683

Method

Fisher exact

Confidence interval

Induration-severe

Statistical analysis description

Difference in incidence rates of induration-severe within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[5]

Method

Fisher exact

Confidence interval

Notes
[5] - Here, "99999" in the p-value signifies not applicable, since no severe induration in both groups.

Erythema-any

Statistical analysis description

Difference in incidence rates of erythema-any within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.203

Method

Fisher exact

Confidence interval

Erythema-mild

Statistical analysis description

Difference in incidence rates of Erythema-Mild within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.399

Method

Fisher exact

Confidence interval

Erythema-moderate

Statistical analysis description

Difference in incidence rates of erythema-moderate within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.382

Method

Fisher exact

Confidence interval

Erythema-severe

Statistical analysis description

Difference in incidence rates of erythema-severe within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[6]

Method

Fisher exact

Confidence interval

Notes
[6] - Here, "99999" in the p-value signifies not applicable, since no severe erythema in both groups.

Any local reaction

Statistical analysis description

Difference in incidence rates of any Local reaction (tenderness, induration, erythema) within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.738

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 3 (14 Weeks of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 3 (14 Weeks of Age)

End point description

Local reactions were reported using an electronic diary by the parent/legal guardian. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration and erythema present); Mild (0.5 cm to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category. Safety population: all subjects who received all 3 doses of the infant series vaccination (14 weeks of age). n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the dose 3 of the infant series (14 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	221	218
Units: Percentage of subjects
number (not applicable)
Tenderness: Any (n= 204,200)	37.3	38
Tenderness: Significant (n= 199,196)	24.1	23.5
Induration: Any (n= 198,195)	17.2	13.8
Induration: Mild (n= 196,195)	15.8	11.8
Induration: Moderate (n= 193,193)	2.6	3.6
Induration: Severe (n= 191,193)	0	0
Erythema: Any (n= 192,195)	10.4	9.7
Erythema: Mild (n= 192,195)	10.4	9.2
Erythema: Moderate (n= 191,193)	0	0.5
Erythema: Severe (n= 191,193)	0	0
Any of the above (n= 206,202)	43.2	42.1

Tenderness-any

Statistical analysis description

Difference in incidence rates of tenderness-any within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.918

Method

Fisher exact

Confidence interval

Tenderness-significant

Statistical analysis description

Difference in incidence rates of tenderness-significant within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.906

Method

Fisher exact

Confidence interval

Induration-any

Statistical analysis description

Difference in incidence rates of induration-any within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.404

Method

Fisher exact

Confidence interval

Induration-mild

Statistical analysis description

Difference in incidence rates of induration-mild within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.305

Method

Fisher exact

Confidence interval

Induration-moderate

Statistical analysis description

Difference in incidence rates of induration-moderate within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.771

Method

Fisher exact

Confidence interval

Induration-severe

Statistical analysis description

Difference in incidence rates of induration-severe within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[7]

Method

Fisher exact

Confidence interval

Notes
[7] - Here, "99999" in the p-value signifies not applicable, since no severe induration in both groups.

Erythema-any

Statistical analysis description

Difference in incidence rates of erythema-any within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.867

Method

Fisher exact

Confidence interval

Erythema-mild

Statistical analysis description

Difference in incidence rates of erythema-mild within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.735

Method

Fisher exact

Confidence interval

Erythema-moderate

Statistical analysis description

Difference in incidence rates of erythema-moderate within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Erythema-severe

Statistical analysis description

Difference in incidence rates of erythema-severe within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[8]

Method

Fisher exact

Confidence interval

Notes
[8] - Here, "99999" in the p-value signifies not applicable, since no severe erythema in both groups.

Any local reaction

Statistical analysis description

Difference in incidence rates of any Local Reaction (tenderness, induration, erythema) within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.842

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

End point description

Local reactions were reported using an electronic diary by the parent/legal guardian. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Induration and erythema were scaled as Any (induration and erythema present); Mild (0.5 cm to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may be represented in more than 1 category. Safety population: all subjects who received toddler dose vaccination(after 12 months). n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the toddler dose (12 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	198	200
Units: Percentage of subjects
number (not applicable)
Tenderness: Any (n= 174,176)	29.9	30.7
Tenderness: Significant (n= 171,170)	15.8	17.1
Induration: Any (n= 173,176)	19.7	17.6
Induration: Mild (n= 170,175)	15.9	14.9
Induration: Moderate (n= 170,171)	5.3	7.6
Induration: Severe (n= 167,169)	0	0
Erythema: Any (n= 174,176)	14.9	14.2
Erythema: Mild (n= 172,175)	12.2	10.9
Erythema: Moderate (n= 169,170)	3.6	4.1
Erythema: Severe (n= 167,169)	0	0
Any of the above (n= 177,178)	36.7	41

Tenderness-any

Statistical analysis description

Difference in incidence rates of tenderness-any within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.908

Method

Fisher exact

Confidence interval

Tenderness-significant

Statistical analysis description

Difference in incidence rates of tenderness-significant within 4 days of the toddler dose, dose 4(12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.772

Method

Fisher exact

Confidence interval

Induration-any

Statistical analysis description

Difference in incidence rates of induration-any within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.681

Method

Fisher exact

Confidence interval

Induration-mild

Statistical analysis description

Difference in incidence rates of induration-mild within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.881

Method

Fisher exact

Confidence interval

Induration-moderate

Statistical analysis description

Difference in incidence rates of induration-moderate within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.509

Method

Fisher exact

Confidence interval

Induration-severe

Statistical analysis description

Difference in incidence rates of induration-severe within 4 days of the toddler dose (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[9]

Method

Fisher exact

Confidence interval

Notes
[9] - Here, "99999" in the p-value signifies not applicable, since no severe induration in both groups.

Erythema-any

Statistical analysis description

Difference in incidence rates of erythema-any within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.88

Method

Fisher exact

Confidence interval

Erythema-mild

Statistical analysis description

Difference in incidence rates of erythema-mild within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.739

Method

Fisher exact

Confidence interval

Erythema-moderate

Statistical analysis description

Difference in incidence rates of erythema-moderate within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Erythema-severe

Statistical analysis description

Difference in incidence rates of erythema-severe within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[10]

Method

Fisher exact

Confidence interval

Notes
[10] - Here, "99999" in the p-value signifies not applicable, since no severe erythema in both groups.

Any local reaction

Statistical analysis description

Difference in incidence rates of any local reaction (tenderness, induration, erythema) within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.446

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 1 (6 Weeks of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 1 (6 Weeks of Age)

End point description

Systemic events (any fever >=38 degrees Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population: all subjects who received at least dose 1 of the infant series vaccination (after 6 weeks). n=number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the dose 1 of the infant series (6 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	353	353
Units: Percentage of subjects
number (not applicable)
Fever >=38 but <=39 degrees C (n= 313,324)	19.8	21.6
Fever >39 but <=40 degrees C (n= 309,322)	2.3	1.2
Fever >40 degrees C (n= 309,322)	0.3	0.9
Decreased appetite (n= 343,347)	55.7	55.9
Irritability (n= 345,347)	83.2	79.8
Increased sleep (n= 338,342)	40.8	36.8
Decreased sleep (n= 336,343)	55.7	56
Any systemic event (n= 350,348)	94.3	90.8

Fever >=38 but <=39 degrees C

Statistical analysis description

Difference in incidence rates of fever >=38 but less than or equal to (<=) 39 degrees C within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.625

Method

Fisher exact

Confidence interval

Fever >39 but <=40 degrees C

Statistical analysis description

Difference in incidence rates of fever >39 but <=40 degrees C within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.375

Method

Fisher exact

Confidence interval

Fever >40 degrees C

Statistical analysis description

Difference in incidence rates of fever >40 degrees C within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.624

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Difference in incidence rates of decreased appetite within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Difference in incidence rates of irritability within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.282

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Difference in incidence rates of Increased sleep within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.307

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Difference in incidence rates of decreased sleep within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.939

Method

Fisher exact

Confidence interval

Any systemic event

Statistical analysis description

Difference in incidence rates of any systemic event (fever, decrease in appetite, irritability, increased or decreased sleep) within 4 days of the infant series dose 1 (6 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

706

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.085

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 2 (10 Weeks of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 2 (10 Weeks of Age)

End point description

Systemic events (any fever >=38 degrees C, decreased appetite, irritability, increased sleep, decreased sleep) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population: all subjects who received dose 2 of the infant series vaccination (10 weeks of age); n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the dose 2 of the infant series (10 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	300	300
Units: Percentage of subjects
number (not applicable)
Fever >=38 but <=39 degrees C (n= 263,249)	10.3	15.3
Fever >39 but <=40 degrees C (n= 259,247)	0.8	0.4
Fever >40 degrees C (n= 259,247)	0	0.4
Decreased appetite (n= 281,282)	48	46.5
Irritability (n= 290,291)	70.7	69.8
Increased sleep (n= 285,275)	33.7	26.9
Decreased sleep (n= 282,286)	37.9	46.9
Any systemic event (n= 294,297)	80.6	80.5

Fever >=38 but <=39 degrees C

Statistical analysis description

Difference in incidence rates of fever >= 38 but <= 39 degrees C within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.111

Method

Fisher exact

Confidence interval

Fever >39 but <=40 degrees C

Statistical analysis description

Difference in incidence rates of fever >39 but <= 40 degrees C within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Fever >40 degrees C

Statistical analysis description

Difference in incidence rates of fever >40 degrees C within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.488

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Difference in incidence rates of Decreased appetite within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.736

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Difference in incidence rates of Irritability within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.856

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Difference in incidence rates of Increased sleep within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.098

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Difference in incidence rates of Decreased sleep within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.034

Method

Fisher exact

Confidence interval

Any systemic event

Statistical analysis description

Difference in incidence rates of Any systemic event (fever, decrease in appetite, irritability, increased or decreased sleep) within 4 days of the infant series dose 2 (10 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

600

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 3 (14 Weeks of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 3 (14 Weeks of Age)

End point description

Systemic events (any fever >=38 degrees C, decreased appetite, irritability, increased sleep, decreased sleep) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population: all subjects who received dose 3 of the infant series vaccination (14 weeks of age). n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the dose 3 of the infant series (14 weeks of age)

End point values	13vPnC: Infant series	7vPnC: Infant Series
Number of subjects analysed	221	218
Units: Percentage of subjects
number (not applicable)
Fever >=38 but <=39 degrees C (n= 181,172)	7.7	14
Fever >39 but <=40 degrees C (n= 179,170)	0	0
Fever >40 degrees C (n= 179,171)	0	0.6
Decreased appetite (n= 202,200)	42.1	41
Irritability (n= 208,208)	64.4	67.3
Increased sleep (n= 199,195)	20.1	20.5
Decreased sleep (n= 205,201)	42.4	36.8
Any systemic event (n= 213,209)	75.1	78.5

Fever >=38 but <=39 degrees C

Statistical analysis description

Difference in incidence rates of fever >= 38 but <= 39 degrees C within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.085

Method

Fisher exact

Confidence interval

Fever >39 but <=40 degrees C

Statistical analysis description

Difference in incidence rates of fever >39 but <= 40 degrees C within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[11]

Method

Fisher exact

Confidence interval

Notes
[11] - Here, "99999" in the p-value signifies not applicable, since no subject with fever > 39 but <= 40 degrees C in both groups.

Fever >40 degrees C

Statistical analysis description

Difference in incidence rates of fever >40 degrees C within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.489

Method

Fisher exact

Confidence interval

Decreased appetite

Statistical analysis description

Difference in incidence rates of decreased appetite within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.84

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Difference in incidence rates of irritability within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.605

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Difference in incidence rates of increased sleep within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Difference in incidence rates of decreased sleep within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.265

Method

Fisher exact

Confidence interval

Any systemic event

Statistical analysis description

Difference in incidence rates of any systemic event (fever, decrease in appetite, irritability, increased or decreased sleep) within 4 days of the infant series dose 3 (14 weeks of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Infant series v 7vPnC: Infant Series

Number of subjects included in analysis

439

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.422

Method

Fisher exact

Confidence interval

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

Top of page

End point title

Percentage of Subjects With Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

End point description

Systemic events (any fever >=38 degrees Celsius [C], decreased appetite, irritability, increased sleep, decreased sleep) were reported using an electronic diary. Subjects may be represented in more than 1 category. Safety population: all subjects who received toddler dose vaccination (12 months of age).n= number of subjects reporting yes for at least 1 day or no for all days for each treatment group respectively.

End point type

Other pre-specified

End point timeframe

Within 4 days after the toddler dose(12 months of age)

End point values	13vPnC: Toddler Dose	7vPnC: Toddler Dose
Number of subjects analysed	198	200
Units: Percentage of subjects
number (not applicable)
Fever >=38 but <=39 degrees C (n= 161,154)	5.6	6.5
Fever >39 but <=40 degrees (n= 160,152)	0.6	0
Fever >40 degrees C (n= 160,152)	0	0
Decreased appetite (n= 174,179)	28.7	24.6
Irritability (n= 174,183)	38.5	35
Increased sleep (n= 171,170)	12.3	9.4
Decreased sleep (n= 172,178)	22.7	27
Any systemic event (n= 179,186)	54.7	52.7

Fever >=38 but <=39 degrees C

Statistical analysis description

Difference in incidence rates of fever >= 38 but <= 39 degrees within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.815

Method

Fisher exact

Confidence interval

Fever >39 but <=40 degrees C

Statistical analysis description

Difference in incidence rates of fever >39 but <= 40 degrees within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

> 0.99

Method

Fisher exact

Confidence interval

Fever >40 degrees C

Statistical analysis description

Difference in incidence rates of fever >40 degrees C within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 99999 ^[12]

Method

Fisher exact

Confidence interval

Notes
[12] - Here, "99999" in the p-value signifies not applicable, since no subject with fever > 40 degrees C in both groups.

Decreased appetite

Statistical analysis description

Difference in incidence rates of decreased appetite within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.401

Method

Fisher exact

Confidence interval

Irritability

Statistical analysis description

Difference in incidence rates of irritability within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.511

Method

Fisher exact

Confidence interval

Increased sleep

Statistical analysis description

Difference in incidence rates of increased sleep within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.487

Method

Fisher exact

Confidence interval

Decreased sleep

Statistical analysis description

Difference in incidence rates of decreased sleep within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.388

Method

Fisher exact

Confidence interval

Any systemic event

Statistical analysis description

Difference in incidence rates of any systemic event fever, decrease in appetite, irritability, increased or decreased sleep) within 4 days of the toddler dose, dose 4 (12 months of age) reported in the 13vPnC group relative to the incidence rates in the 7vPnC group. No hypothesis testing was performed. The analysis is descriptive.

Comparison groups

13vPnC: Toddler Dose v 7vPnC: Toddler Dose

Number of subjects included in analysis

398

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.753

Method

Fisher exact

Confidence interval

Adverse events

Top of page

Timeframe for reporting adverse events

AEs were recorded from signing of ICF to 1 month after infant series and toddler dose to 1 month after toddler dose. SAEs were recorded from signing of ICF to 1 month after toddler dose. Local and systemic events assessed within 4 days of each vaccination

Adverse event reporting additional description

Safety population = all randomized subjects with at least 1 dose of study treatment. An Adverse Event (AE) term may be reported as both a serious and non-serious AE, but are distinct events. AE may = serious for 1 subject and = non-serious for another subject or subject may have experienced both a serious and non-serious episode of the same event.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

12.1

Reporting group title

Infant Series 13vPnC

Reporting group description

Subjects received 1 single 0.5 mL dose of 13vPnC, administered intramuscularly, at 6, 10 and 14 weeks of age (infant series), co-administered with a commercially available combination vaccine containing DTP-Hib-HBV and a commercially available OPV.

Reporting group title

Infant Series 7vPnC

Reporting group description

Subjects received 1 single 0.5 mL dose of 7vPnC, administered intramuscularly, at 6, 10 and 14 weeks of age (infant series), co-administered with a commercially available combination vaccine containing DTP-Hib-HBV and a commercially available OPV.

Reporting group title

After the Infant Series 13vPnC

Reporting group description

Subjects received 1 single 0.5 mL dose of 13vPnC, administered intramuscularly, at 6, 10 and 14 weeks of age (infant series), co-administered with a commercially available combination vaccine DTP-Hib-HBV and a commercially available OPV. AEs were collected from approximately 1 month after Dose 3 to the Toddler dose.

Reporting group title

After the Infant Series 7vPnC

Reporting group description

Reporting group title

Toddler Dose 13vPnC

Reporting group description

Subjects received 1 single 0.5 mL dose of 13vPnC, administered intramuscularly, at 12 months of age (toddler dose).

Reporting group title

Toddler Dose 7vPnC

Reporting group description

Subjects received 1 single 0.5 mL dose of 7vPnC, administered intramuscularly, at 12 months of age (toddler dose).

Serious adverse events	Infant Series 13vPnC	Infant Series 7vPnC	After the Infant Series 13vPnC	After the Infant Series 7vPnC	Toddler Dose 13vPnC	Toddler Dose 7vPnC
Total subjects affected by serious adverse events
subjects affected / exposed	8 / 353 (2.27%)	6 / 353 (1.70%)	8 / 353 (2.27%)	11 / 353 (3.12%)	4 / 198 (2.02%)	1 / 200 (0.50%)
number of deaths (all causes)	0	0	0	1	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pneumonitis
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory arrest
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Breath holding
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	1 / 200 (0.50%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Heart disease congenital
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac failure congestive
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Infantile colic
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatosplenomegaly
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Drug eruption
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	2 / 353 (0.57%)	4 / 353 (1.13%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	3 / 353 (0.85%)	0 / 353 (0.00%)	1 / 353 (0.28%)	1 / 353 (0.28%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis bacterial
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	4 / 353 (1.13%)	2 / 198 (1.01%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 4	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection viral
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysentery
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral myocarditis
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypocalcaemia
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Infant Series 13vPnC	Infant Series 7vPnC	After the Infant Series 13vPnC	After the Infant Series 7vPnC	Toddler Dose 13vPnC	Toddler Dose 7vPnC
Total subjects affected by non serious adverse events
subjects affected / exposed	330 / 353 (93.48%)	316 / 353 (89.52%)	5 / 353 (1.42%)	9 / 353 (2.55%)	98 / 198 (49.49%)	98 / 200 (49.00%)
Vascular disorders
Pallor
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	1 / 200 (0.50%)
occurrences all number	0	0	0	0	1	1
Pregnancy, puerperium and perinatal conditions
Umbilical granuloma
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	75 / 353 (21.25%)	70 / 353 (19.83%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	131	118	0	0	0	0
Injection site swelling
subjects affected / exposed	55 / 353 (15.58%)	57 / 353 (16.15%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	89	83	0	0	0	0
Pyrexia
subjects affected / exposed	29 / 353 (8.22%)	21 / 353 (5.95%)	0 / 353 (0.00%)	0 / 353 (0.00%)	2 / 198 (1.01%)	6 / 200 (3.00%)
occurrences all number	31	22	0	0	2	6
Injection site erythema
subjects affected / exposed	12 / 353 (3.40%)	12 / 353 (3.40%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	15	14	0	0	0	0
Injection site nodule
subjects affected / exposed	5 / 353 (1.42%)	12 / 353 (3.40%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	5	12	0	0	0	0
Irritability
subjects affected / exposed	1 / 353 (0.28%)	3 / 353 (0.85%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	3	0	0	0	0
Tenderness
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Fever ≥38°C but ≤39°C Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[1]	62 / 313 (19.81%)	70 / 324 (21.60%)	0 / 353 (0.00%)	0 / 353 (0.00%)	9 / 161 (5.59%)	10 / 154 (6.49%)
occurrences all number	62	70	0	0	9	10
Fever >39°C but ≤40°C Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[2]	7 / 309 (2.27%)	4 / 322 (1.24%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 160 (0.63%)	0 / 152 (0.00%)
occurrences all number	7	4	0	0	1	0
Fever >40°C Dose Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[3]	1 / 309 (0.32%)	3 / 322 (0.93%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 160 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	3	0	0	0	0
Decreased appetite Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[4]	191 / 343 (55.69%)	194 / 347 (55.91%)	0 / 353 (0.00%)	0 / 353 (0.00%)	50 / 174 (28.74%)	44 / 179 (24.58%)
occurrences all number	191	194	0	0	50	44
Irritability Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[5]	287 / 345 (83.19%)	277 / 347 (79.83%)	0 / 353 (0.00%)	0 / 353 (0.00%)	67 / 174 (38.51%)	64 / 183 (34.97%)
occurrences all number	287	277	0	0	67	64
Increased sleep Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[6]	138 / 338 (40.83%)	126 / 342 (36.84%)	0 / 353 (0.00%)	0 / 353 (0.00%)	21 / 171 (12.28%)	16 / 170 (9.41%)
occurrences all number	138	126	0	0	21	16
Decreased sleep Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[7]	187 / 336 (55.65%)	192 / 343 (55.98%)	0 / 353 (0.00%)	0 / 353 (0.00%)	39 / 172 (22.67%)	48 / 178 (26.97%)
occurrences all number	187	192	0	0	39	48
Fever ≥38°C but ≤39°C Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[8]	27 / 263 (10.27%)	38 / 249 (15.26%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	27	38	0	0	0	0
Fever >39°C but ≤40°C Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[9]	2 / 259 (0.77%)	1 / 247 (0.40%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	1	0	0	0	0
Decreased appetite Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[10]	135 / 281 (48.04%)	131 / 282 (46.45%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	135	131	0	0	0	0
Fever >40°C Dose Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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]	0 / 259 (0.00%)	1 / 247 (0.40%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Irritability Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[12]	205 / 290 (70.69%)	203 / 291 (69.76%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	205	203	0	0	0	0
Increased sleep Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[13]	96 / 285 (33.68%)	74 / 275 (26.91%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	96	74	0	0	0	0
Decreased sleep Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[14]	107 / 282 (37.94%)	134 / 286 (46.85%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	107	134	0	0	0	0
Fever ≥38°C but ≤39°C Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[15]	14 / 181 (7.73%)	24 / 172 (13.95%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	14	24	0	0	0	0
Fever >40°C Dose Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[16]	0 / 179 (0.00%)	1 / 171 (0.58%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Decreased appetite Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[17]	85 / 202 (42.08%)	82 / 200 (41.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	85	82	0	0	0	0
Irritability Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[18]	134 / 208 (64.42%)	140 / 208 (67.31%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	134	140	0	0	0	0
Increased sleep Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[19]	40 / 199 (20.10%)	40 / 195 (20.51%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	40	40	0	0	0	0
Decreased sleep Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for SE is same as data collected through ediaries 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 ^[20]	87 / 205 (42.44%)	74 / 201 (36.82%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	87	74	0	0	0	0
Immune system disorders
Allergy to arthropod bite
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences all number	0	0	0	0	1	0
Reproductive system and breast disorders
Penile adhesion
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	37 / 353 (10.48%)	40 / 353 (11.33%)	0 / 353 (0.00%)	2 / 353 (0.57%)	5 / 198 (2.53%)	6 / 200 (3.00%)
occurrences all number	41	49	0	2	6	6
Upper airway obstruction
subjects affected / exposed	1 / 353 (0.28%)	3 / 353 (0.85%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	3	0	1	0	0
Nasal congestion
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Productive cough
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Wheezing
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Bronchial hyperreactivity
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	1	1	0	0
Rhinitis allergic
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Asthma
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences all number	0	0	0	0	1	0
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Limb injury
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Congenital, familial and genetic disorders
Macrocephaly
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	0	0	1	0	0
Phimosis
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences all number	0	0	0	0	1	0
Cardiac disorders
Ventricular extrasystoles
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Nervous system disorders
Crying
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Convulsion
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Somnolence
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Febrile convulsion
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	0	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	2 / 200 (1.00%)
occurrences all number	0	0	0	0	1	3
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Otorrhoea
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Eye disorders
Eye discharge
subjects affected / exposed	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	1	0	0	0	0
Lacrimation increased
subjects affected / exposed	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	21 / 353 (5.95%)	26 / 353 (7.37%)	1 / 353 (0.28%)	0 / 353 (0.00%)	1 / 198 (0.51%)	3 / 200 (1.50%)
occurrences all number	24	29	1	0	1	3
Vomiting
subjects affected / exposed	4 / 353 (1.13%)	6 / 353 (1.70%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	4	6	0	0	0	0
Constipation
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Infantile colic
subjects affected / exposed	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	3	0	0	0	0	0
Abdominal discomfort
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Flatulence
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Perianal erythema
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	2 / 353 (0.57%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	2	0	0	0	0
Seborrhoeic dermatitis
subjects affected / exposed	2 / 353 (0.57%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	3	2	0	0	0	0
Rash papular
subjects affected / exposed	1 / 353 (0.28%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	2	0	0	0	0
Alopecia
subjects affected / exposed	0 / 353 (0.00%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	2	0	0	0	0
Rash
subjects affected / exposed	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	0	0	0	0	0
Skin hypopigmentation
subjects affected / exposed	0 / 353 (0.00%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	2	0	0	0	0
Acne infantile
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Dandruff
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Dermatitis
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Rash generalised
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Urticaria
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	0	1	0	0	0
Tenderness (Any) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[21]	217 / 347 (62.54%)	207 / 347 (59.65%)	0 / 353 (0.00%)	0 / 353 (0.00%)	52 / 174 (29.89%)	54 / 176 (30.68%)
occurrences all number	217	207	0	0	52	54
Tenderness (Significant) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[22]	144 / 341 (42.23%)	139 / 343 (40.52%)	0 / 353 (0.00%)	0 / 353 (0.00%)	27 / 171 (15.79%)	29 / 170 (17.06%)
occurrences all number	144	139	0	0	27	29
Induration (Any) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[23]	73 / 339 (21.53%)	77 / 342 (22.51%)	0 / 353 (0.00%)	0 / 353 (0.00%)	34 / 173 (19.65%)	31 / 176 (17.61%)
occurrences all number	73	77	0	0	34	31
Induration (Mild) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[24]	65 / 338 (19.23%)	65 / 340 (19.12%)	0 / 353 (0.00%)	0 / 353 (0.00%)	27 / 170 (15.88%)	26 / 175 (14.86%)
occurrences all number	65	65	0	0	27	26
Induration (Moderate) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[25]	16 / 331 (4.83%)	19 / 338 (5.62%)	0 / 353 (0.00%)	0 / 353 (0.00%)	9 / 170 (5.29%)	13 / 171 (7.60%)
occurrences all number	16	19	0	0	9	13
Erythema (Any) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[26]	42 / 333 (12.61%)	45 / 339 (13.27%)	0 / 353 (0.00%)	0 / 353 (0.00%)	26 / 174 (14.94%)	25 / 176 (14.20%)
occurrences all number	42	45	0	0	26	25
Erythema (Mild) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[27]	38 / 333 (11.41%)	40 / 338 (11.83%)	0 / 353 (0.00%)	0 / 353 (0.00%)	21 / 172 (12.21%)	19 / 175 (10.86%)
occurrences all number	38	40	0	0	21	19
Erythema (Moderate) Infant Series Dose 1 and Toddler Dose
Additional description: Dose 1 and Toddler Dose: Subjects affected and occurrences for LR 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 ^[28]	5 / 330 (1.52%)	6 / 337 (1.78%)	0 / 353 (0.00%)	0 / 353 (0.00%)	6 / 169 (3.55%)	7 / 170 (4.12%)
occurrences all number	5	6	0	0	6	7
Tenderness (Any) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[29]	126 / 284 (44.37%)	124 / 282 (43.97%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	126	124	0	0	0	0
Tenderness (Significant) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[30]	74 / 278 (26.62%)	78 / 279 (27.96%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	74	78	0	0	0	0
Induration (Any) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[31]	58 / 281 (20.64%)	52 / 278 (18.71%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	58	52	0	0	0	0
Induration (Mild) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[32]	47 / 281 (16.73%)	45 / 277 (16.25%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	47	45	0	0	0	0
Induration (Moderate) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[33]	14 / 273 (5.13%)	11 / 272 (4.04%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	14	11	0	0	0	0
Erythema (Any) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[34]	38 / 275 (13.82%)	50 / 280 (17.86%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	38	50	0	0	0	0
Erythema (Mild) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[35]	36 / 275 (13.09%)	44 / 279 (15.77%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	36	44	0	0	0	0
Erythema (Moderate) Infant Series Dose 2
Additional description: Dose 2: Subjects affected and occurrences for LR 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 ^[36]	4 / 273 (1.47%)	8 / 273 (2.93%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	4	8	0	0	0	0
Tenderness (Any) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[37]	76 / 204 (37.25%)	76 / 200 (38.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	76	76	0	0	0	0
Tenderness (Significant) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[38]	48 / 199 (24.12%)	46 / 196 (23.47%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	48	46	0	0	0	0
Induration (Any) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[39]	34 / 198 (17.17%)	27 / 195 (13.85%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	34	27	0	0	0	0
Induration (Mild) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[40]	31 / 196 (15.82%)	23 / 195 (11.79%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	31	23	0	0	0	0
Induration (Moderate) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[41]	5 / 193 (2.59%)	7 / 193 (3.63%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	5	7	0	0	0	0
Erythema (Any) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[42]	20 / 192 (10.42%)	19 / 195 (9.74%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	20	19	0	0	0	0
Erythema (Mild) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[43]	20 / 192 (10.42%)	18 / 195 (9.23%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	20	18	0	0	0	0
Erythema (Moderate) Infant Series Dose 3
Additional description: Dose 3: Subjects affected and occurrences for LR 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 ^[44]	0 / 191 (0.00%)	1 / 193 (0.52%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Rickets
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	0	0	1	0	0
Infections and infestations
Rhinitis
subjects affected / exposed	47 / 353 (13.31%)	37 / 353 (10.48%)	0 / 353 (0.00%)	3 / 353 (0.85%)	1 / 198 (0.51%)	4 / 200 (2.00%)
occurrences all number	57	50	0	3	1	4
Upper respiratory tract infection
subjects affected / exposed	39 / 353 (11.05%)	45 / 353 (12.75%)	2 / 353 (0.57%)	2 / 353 (0.57%)	11 / 198 (5.56%)	6 / 200 (3.00%)
occurrences all number	56	53	2	2	13	6
Nasopharyngitis
subjects affected / exposed	11 / 353 (3.12%)	17 / 353 (4.82%)	0 / 353 (0.00%)	1 / 353 (0.28%)	1 / 198 (0.51%)	2 / 200 (1.00%)
occurrences all number	14	20	0	1	1	2
Gastroenteritis
subjects affected / exposed	8 / 353 (2.27%)	5 / 353 (1.42%)	0 / 353 (0.00%)	0 / 353 (0.00%)	2 / 198 (1.01%)	3 / 200 (1.50%)
occurrences all number	10	5	0	0	2	3
Lower respiratory tract infection
subjects affected / exposed	5 / 353 (1.42%)	2 / 353 (0.57%)	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	5	2	1	1	0	0
Bronchiolitis
subjects affected / exposed	4 / 353 (1.13%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences all number	4	2	0	0	1	0
Respiratory tract infection
subjects affected / exposed	2 / 353 (0.57%)	3 / 353 (0.85%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	3	0	0	0	0
Bronchopneumonia
subjects affected / exposed	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	1	0	0	0	0
Otitis media
subjects affected / exposed	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	1	0	0	0	0
Viral infection
subjects affected / exposed	2 / 353 (0.57%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	1 / 200 (0.50%)
occurrences all number	2	1	0	0	0	1
Acarodermatitis
subjects affected / exposed	0 / 353 (0.00%)	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences all number	0	2	0	0	1	0
Omphalitis
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	1	0	0	0	0
Viral diarrhoea
subjects affected / exposed	2 / 353 (0.57%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	1 / 200 (0.50%)
occurrences all number	1	1	0	0	0	1
Abscess neck
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Body tinea
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	1	0	0	0
Bronchitis
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	2	0	0	0	0	0
Fungal infection
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Impetigo
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Otitis externa
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Rash pustular
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	0	0
Respiratory tract infection viral
subjects affected / exposed	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 198 (0.51%)	0 / 200 (0.00%)
occurrences all number	1	0	0	0	1	0
Viral rash
subjects affected / exposed	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	1	0	0	0	0
Tuberculosis
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	1 / 353 (0.28%)	0 / 198 (0.00%)	0 / 200 (0.00%)
occurrences all number	0	0	0	1	0	0
Furuncle
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	1 / 200 (0.50%)
occurrences all number	0	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 353 (0.00%)	0 / 198 (0.00%)	1 / 200 (0.50%)
occurrences all number	0	0	0	0	0	1

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[16] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[17] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[18] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[19] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[20] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[21] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[22] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[23] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[24] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[25] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[26] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[27] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[28] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[29] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[30] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[31] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[32] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[33] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[34] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[35] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[36] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[37] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[38] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[39] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[40] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[41] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[42] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[43] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.
[44] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: Here number of subjects exposed signifies subjects reporting yes for at least 1 day or no for all days.

More information

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Were there any global substantial amendments to the protocol? Yes

29 Aug 2007

1- Volume of blood samples reduced from 5mL to 3mL based on the actual weight of babies enrolled in the study as some infants were too small for a 5-mL blood draw at 18 weeks of age as specified in the study protocol. 2- An additional inclusion criterion of subject weight of 3.5 kg or greater at the time of enrollment was added.

13 Feb 2008

1- A cohort 2 was added to the study because the original subjects would not be fully representative of a 6-, 10-, and 14-week infant series schedule owing to the clinical hold. 2- Analysis endpoint for the pertussis responses was modified from the specific cutoff of 5 EU/mL to a comparison based on the level of serum IgG attained by 95% of subjects in the 7vPnC group. 3- Coprimary whole-cell pertussis antigens endpoint was changed to a primary endpoint. 4- A second interim analysis for the cohort 2 infant series was allowed.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
10 Oct 2007	This study was placed temporarily on clinical hold to allow review of safety data. It was suspended based on the review of 4 serious adverse events (SAEs) reported as serious, unexpected, and possibly related by investigators from studies of 13vPnC or 7vPnC conducted outside of India. All 4 of the SAEs considered to be possibly related to vaccine by the investigator and reviewed by the Drug Controller General of India DCG(I) occurred in subjects who received the comparator 7vPnC, that is (ie), Prevenar.	01 Dec 2007
07 Nov 2008	The study was put temporarily on hold at all sites due to the death of a subject. This occurred 1 week after administration of the 14-week vaccination. The SAE was reported as possibly related to test article, and a report was generated. The investigator subsequently changed the causality assessment to “not related” to vaccination.	01 Apr 2009

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, Randomised, Active-Controlled, Double-Blind Trial Evaluating the Safety, Tolerability and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Paediatric Vaccinations in India

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to (>=) 0.35 Micrograms per Milliliter (mcg/mL), 1 Month After the Infant Series.

Primary: Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to (>=) 0.35 Micrograms per Milliliter (mcg/mL), 1 Month After the Infant Series.

Primary: Percentage of Subjects Achieving a Predefined Antibody Level for Concomitant Vaccine Pertussis Antigens (Pertussis Toxoid [PT], Filamentous Hemagglutinin [FHA], Pertactin [PRN]), 1 Month After the Infant Series.

Primary: Percentage of Subjects Achieving a Predefined Antibody Level for Concomitant Vaccine Pertussis Antigens (Pertussis Toxoid [PT], Filamentous Hemagglutinin [FHA], Pertactin [PRN]), 1 Month After the Infant Series.

Secondary: Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to 0.35 Mcg/mL, 1 Month After the Toddler Dose.

Secondary: Percentage of Subjects Achieving a Predefined Antibody Level of Greater Than or Equal to 0.35 Mcg/mL, 1 Month After the Toddler Dose.

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody, 1 Month After the 3-Dose Infant Series

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody, 1 Month After the 3-Dose Infant Series

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal IgG Antibody, 1 Month After the Toddler Dose

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal IgG Antibody, 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 1 (6 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 1 (6 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 2 (10 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 2 (10 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 3 (14 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Infant Series Dose 3 (14 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Local Reactions: Toddler Dose (12 Months of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 1 (6 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 1 (6 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 2 (10 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 2 (10 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 3 (14 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Infant Series Dose 3 (14 Weeks of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

Other pre-specified: Percentage of Subjects With Pre-specified Systemic Events: Toddler Dose (12 Months of Age)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Randomised, Active-Controlled, Double-Blind Trial Evaluating the Safety, Tolerability and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants Given With Routine Paediatric Vaccinations in India