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Clinical Trial Results:
A phase 3, randomized, Active-Controlled, Double-blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healhy Infants Given With Routine Pediatric Vaccination in Italy

Summary
EudraCT number	2005-004771-38
Trial protocol	IT
Global end of trial date	21 Feb 2008

Results information
Results version number	v1(current)
This version publication date	29 Jun 2016
First version publication date	02 Aug 2015
Other versions

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

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Trial information

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Sponsor protocol code

6096A1-500

ISRCTN number

US NCT number

NCT00366899

WHO universal trial number (UTN)

Other trial identifiers

Alias: B1851096

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

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

Scientific contact

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

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000036-PIP01-07

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

11 Sep 2008

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Feb 2008

Was the trial ended prematurely?

Main objective of the trial

-To evaluate the acceptability of the safety profile of 13vPnC as measured by the incidence rates of local injection site reactions, systemic events, and adverse events (AEs) . - To demonstrate that the immune response induced by Infanrix hexa given with 13vPnC is noninferior to the immune response induced by Infanrix hexa given with 7vPnC when measured 1 month after the toddler dose. Response to the following antigen in Infanrix hexa was assessed: hepatitis B. -- To assess the immune response to 13vPnC 1 month after the infant series as measured by serum immunoglobulin G (IgG) responses. To assess the immune response to 13vPnC before the toddler dose as measured by serum IgG responses.

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 Oct 2006

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Italy: 606

Worldwide total number of subjects

606

EEA total number of subjects

606

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)

606

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were recruited in Italy from October 2006 to March 2007.

Screening details

Subjects were enrolled into the study according to inclusion/exclusion criteria without a screening period. One subject was prerandomized and counted twice.

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 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with diphtheria-tetanus-acellular pertussis (DTPa), hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b (Hib) vaccine (Infanrix hexa) in infant series. At the start, one subject was counted twice, one subject randomized to 13vPnC, incorrectly received 7vPnC. At vaccine dose 1, two subjects randomized to 13vPnC, incorrectly received 7vPnC. At vaccine dose 2, one subject randomized to 13vPnC, incorrectly received 7vPnC.

Arm type

Experimental

Investigational medicinal product name

Infanrix hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5-mL dose of DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) in infant series.

Investigational medicinal product name

13vPnc

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 13vPnC at 3 and 5 months (infant series).

7vPnC Infant Series

Arm description

Subjects received 7-valent pneumococcal conjugate vaccine (7vPnC) coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) in infant series. At the start, one subject randomized to 7vPnC but never vaccinated.

Arm type

Active comparator

Investigational medicinal product name

Infanrix hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of DTPa, hepatitis B, inactivated poliovirus, Hib vaccine (Infanrix hexa) in infant series.

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 7vPnC at 3 and 5 months (infant series).

Number of subjects in period 1	13vPnC Infant Series	7vPnC Infant Series
Started	303	303
Vaccinated Dose 1	302	302
Vaccinated Dose 2	296	293
Completed	294	291
Not completed	9	12
Consent withdrawn by subject	4	7
'Protocol Violation '	2	1
'Randomized but not consented '	1	-
Failed to return	1	1
'Adverse Event '	-	1
'Physician Decision '	1	-
Lost to follow-up	-	2

Period 2 title

After Infant series

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

13vPnC After Infant Series

Arm description

Included subjects who received 13vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) in infant series.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

7vPnC After Infant Series

Arm description

Included subjects who received 7vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) in 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	294	291
Completed	287	282
Not completed	7	9
Consent withdrawn by subject	1	4
'Protocol Violation '	1	-
'Adverse Event '	1	2
Lost to follow-up	4	3

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 13vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) at toddler dose.

Arm type

Experimental

Investigational medicinal product name

13vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 13vPnC at 11 months of age (toddler dose).

Investigational medicinal product name

Infanrix hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) at 11 months of age (toddler dose).

7vPnC Toddler Dose

Arm description

Subjects received 7vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) at toddler dose.

Arm type

Active comparator

Investigational medicinal product name

Infanrix hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 0.5 mL dose of DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) at 11 months of age (toddler dose).

Investigational medicinal product name

7vPnC

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received one single 0.5 mL dose of 7vPnC at 11 months of age (toddler dose).

Number of subjects in period 3	13vPnC Toddler Dose	7vPnC Toddler Dose
Started	287	282
Completed	285	281
Not completed	2	1
Consent withdrawn by subject	1	1
'Protocol Violation '	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

Reporting group values	13vPnC Infant Series	7vPnC Infant Series	Total
Number of subjects	303	303	606
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	2.9 ( 0.3 )	2.9 ( 0.3 )	-
Gender categorical
Units: Subjects
Female	138	133	271
Male	164	170	334
Unknown	1	0	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

Reporting group title

13vPnC After Infant Series

Reporting group description

Included subjects who received 13vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) in infant series.

Reporting group title

7vPnC After Infant Series

Reporting group description

Included subjects who received 7vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) in infant series.

Reporting group title

13vPnC Toddler Dose

Reporting group description

Subjects received 13vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) at toddler dose.

Reporting group title

7vPnC Toddler Dose

Reporting group description

Subjects received 7vPnC coadministered with DTPa, hepatitis B, inactivated poliovirus, and Hib vaccine (Infanrix hexa) at toddler dose.

Subject analysis set title

13vPnC Dose 1

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Infanrix hexa at 3 months of age.

Subject analysis set title

7vPnC Dose 1

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with Infanrix hexa at 3 months of age.

Subject analysis set title

13vPnC Toddler Dose

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Infanrix hexa at 11 months of age.

Subject analysis set title

7vPnC Dose 2

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with Infanrix hexa at 5 months of age.

Subject analysis set title

13vPnC Dose 2

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Infanrix hexa at 5 months of age.

Subject analysis set title

7vPnC Toddler Dose

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with Infanrix hexa at 11 months of age.

Subject analysis set title

7vPnC After 2-Dose Infant Series

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with Infanrix hexa at 3 and 5 months of age (infant series).

Subject analysis set title

13vPnC After 2-Dose Infant Series

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Infanrix hexa at 3 and 5 months of age (infant series).

Subject analysis set title

7vPnC After Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 7vPnC coadministered with Infanrix hexa at 11 months of age (toddler dose).

Subject analysis set title

13vPnC After Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Infanrix hexa at 11 months of age (toddler dose).

Subject analysis set title

13vPnC Before Toddler Dose

Subject analysis set type

Per protocol

Subject analysis set description

Subjects received one single 0.5 mL dose of 13vPnC coadministered with Infanrix hexa at 11 months of age (toddler dose).

Primary: Percentage of Subjects Reporting Pre-Specified Local Reactions

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End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions ^[1]

End point description

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

End point type

Primary

End point timeframe

During the 4-day period after each dose

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	7vPnC Dose 1	13vPnC Dose 1	13vPnC Toddler Dose	7vPnC Dose 2	13vPnC Dose 2	7vPnC Toddler Dose
Number of subjects analysed	255	243	204	226	225	200
Units: Percentage of Subjects
number (not applicable)
Tenderness - Any (n=234,243,214,215,199,188)	30	32.1	47.2	36.7	30.4	44.1
Tenderness-Significant (n=224,231,199,199,164,153)	3.5	2.7	8.5	5	4.5	5.9
Swelling - Any (n=232,240,207,209,175,165)	19.6	19	28.6	28.7	24.6	27.3
Swelling - Mild (n=232,240,207,208,174,161)	18.3	17.7	26.4	26.4	21.7	21.7
Swelling - Moderate (n=223,229,198,195,160,157)	3.1	3.6	7.5	5.1	5.6	10.2
Swelling - Severe (n=222,229,197,194,159,152)	0	0	0	0	0	0
Redness - Any (n=233,245,213,212,178,174)	26.5	25.8	36.5	34.4	31.5	36.2
Redness - Mild (n=233,244,211,211,178,172)	24.6	24	32.6	32.2	28.4	30.8
Redness - Moderate (n=222,231,200,195,160,156)	3	2.7	7.5	3.6	5.5	10.9
Redness - Severe (n=222,229,197,194,159,152)	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Subjects Reporting Pre-Specified Systemic Events

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End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events ^[2]

End point description

Systemic events (fever greater than or equal to [≥]37.5 degrees Celsius [C], fever ≥38 C but less than or equal to [≤]39 C, fever greater than [>]39 C but ≤40 C, fever >40 C, decreased appetite, irritability, increased sleep, decreased sleep, hives, use of medication (meds) to treat symptoms, and use of medication to prevent symptoms) were reported using an electronic diary. Subjects may be represented in more than 1 category. The safety population included all subjects who received at least 1 dose of vaccine, (n) = number of subjects reporting yes for at least 1 day or no for all days.

End point type

Primary

End point timeframe

During the 4-day period after each dose

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	7vPnC Dose 1	13vPnC Dose 1	13vPnC Toddler Dose	7vPnC Dose 2	13vPnC Dose 2	7vPnC Toddler Dose
Number of subjects analysed	286	291	245	260	269	249
Units: Percentage of Subjects
number (not applicable)
Fever ≥38°C but ≤39°C (n=247,246,227,226,204,197)	38.6	41.7	63.7	60.6	55.5	52.3
Fever >39°C but ≤40°C (n=224,233,204,201,167,160)	4.7	3.6	9.6	7	6.9	12.5
Fever >40°C (n=222,230,198,195,160,152)	0	0	0	0	0	0.7
Decreased appetite (n=246,248,220,218,198,197)	34.3	35.4	52	45.4	47.3	57.4
Irritability (n=258,259,245,243,221,227)	63.7	72.9	74.7	75.3	75.5	74.9
Increased sleep (n=269,276,226,232,195,196)	64.5	65.8	53.8	56.5	57.1	54.6
Decreased sleep (n=244,242,222,213,180,171)	36.4	39.3	35.6	41.8	40.1	35.7
Meds-treat symptoms (n=244,245,219,228,192,190)	30.6	34.8	53.1	47.8	43.4	43.7
Meds-prevent symptoms (n=230,238,208,208,172,169)	18.1	12.6	27.9	24.5	20.2	24.3

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving Predefined Antibody Levels for Concomitant Antigen Pertussis, Hepatitis B, Haemophilus influenzae Type b, Diphtheria, Tetanus and Polio After the 2-Dose Infant Series and After the Toddler Dose

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End point title

Percentage of Subjects Achieving Predefined Antibody Levels for Concomitant Antigen Pertussis, Hepatitis B, Haemophilus influenzae Type b, Diphtheria, Tetanus and Polio After the 2-Dose Infant Series and After the Toddler Dose

End point description

Percentage of Subjects achieving predefined antibody threshold levels for Pertussis Toxoid (PT) ≥5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL), Filamentous Haemagglutinin (FHA) ≥5 or ≥7.82 EU/mL, and Pertactin (PRN) ≥5 EU/mL, ≥10.0 Milli-International Units Per Milliliter (mIU/mL) for Hepatitis B, Hib 0.15 microgram (μg)/mL, 0.01 or 0.1 IU/mL for Diphtheria, 0.1 IU/mL for Tetanus, and ≥1:8 titer for Polio (Type 1, 2, and 3) with the corresponding 95 percent (%) confidence interval (CI) for antigens are presented. Evaluable immunogenicity (per protocol) population who adhered to the protocol requirements, had valid and determinate assay results, and had no other major protocol violations; (n) = number of subjects with a determinate postinfant antibody concentration/titer for the given concomitant antigen.

End point type

Primary

End point timeframe

One month after the infant series (6 months of age) and after the toddler dose (12 months of age)

End point values	13vPnC After 2-Dose Infant Series	7vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	275	279	254	261
Units: percentage of subjects
number (confidence interval 95%)
Pertussis, PT ≥5 EU/mL (n=250,272,235,219)	99.6 (97.8 to 100)	100 (98.7 to 100)	100 (98.4 to 100)	100 (98.1 to 100)
Pertussis, FHA ≥5 EU/mL (n=243,272,229,214)	100 (98.5 to 100)	100 (98.7 to 100)	100 (98.4 to 100)	100 (86.9 to 97.7)
Pertussis, FHA ≥7.82 EU/mL (n=243,272,229,214)	100 (98.5 to 100)	100 (98.7 to 100)	100 (98.4 to 100)	100 (98 to 100)
Pertactin ≥5 EU/mL (n=248,270,234,217)	100 (98.5 to 100)	100 (98.6 to 100)	100 (98.4 to 100)	100 (97.9 to 100)
Hepatitis B ≥ 10.0 mIU/mL	93.8 (90.2 to 96.3)	93.1 (89.5 to 95.8)	98.4 (96 to 99.6)	98.8 (97.9 to 100)
Haemophilus influenzae type b 0.15 μg/mL	87 (82 to 91.1)	90.3 (86.1 to 93.5)	99.6 (97.7 to 100)	98.2 (91.8 to 97.8)
Haemophilus influenzae type b 1.0 μg/mL	49.4 (42.7 to 56)	48.7 (42.6 to 54.9)	96.2 (92.9 to 98.2)	92.2 (91.6 to 97.7)
Diptheria 0.01 IU/mL (n=207,240,164,190)	100 (98.2 to 100)	100 (98.5 to 100)	100 (97.8 to 100)	100 (91.7 to 97.8)
Diptheria 0.1 IU/mL (n=207,240,164,190)	92.8 (88.3 to 95.9)	96.3 (93 to 98.3)	100 (97.8 to 100)	100 (98.1 to 100)
Tetanus 0.1 IU/mL (n=155,214,125,96)	94.2 (89.3 to 97.3)	92.5 (88.1 to 95.7)	97.6 (93.1 to 99.5)	93.8 (98.3 to 100)
Polio, Type 1 ≥1:8	99.5 (97.3 to 100)	99.6 (97.9 to 100)	100 (97.7 to 100)	100 (98.3 to 100)
Polio, Type 2 ≥1:8	95.6 (91.8 to 98)	96.6 (93.6 to 98.4)	100 (97.6 to 100)	100 (98.3 to 100)
Polio, Type 3 ≥1:8	99.5 (97.3 to 100)	98.9 (96.7 to 99.8)	100 (97.6 to 100)	100 (96.6 to 99.8)
Pertussis, PT (infant ≥16; Toddler ≥21) EU/mL	95.2 (91.8 to 97.5)	95.2 (92 to 97.4)	92.8 (88.7 to 95.7)	95.4 (95.4 to 99.5)
Pertussis, FHA (Infant ≥31; Toddler ≥162) EU/mL	94.7 (91 to 97.1)	95.6 (92.4 to 97.7)	95.2 (91.6 to 97.6)	95.3 (87.8 to 95.4)
Pertactin (Infant ≥40; Toddler ≥106) EU/mL	91.9 (87.8 to 95)	95.2 (91.9 to 97.4)	94.9 (91.2 to 97.3)	95.4 (98.1 to 100)

Pertussis PT ≥5 EU/mL

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-2.2

upper limit

Notes
[3] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis PT ≥16 EU/mL

Statistical analysis description

For Pertussis PT the difference in percentages between the two groups (13vPnC – 7vPnC) at ≥16 EU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-4

upper limit

3.8

Notes
[4] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis FHA ≥5 EU/mL

Statistical analysis description

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

Comparison groups

7vPnC After 2-Dose Infant Series v 13vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.4

Notes
[5] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis FHA ≥7.82 EU/mL

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.4

Notes
[6] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis FHA ≥31 EU/mL

Statistical analysis description

For Pertussis FHA the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥31 EU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

2.9

Notes
[7] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertactin ≥5 EU/mL

Statistical analysis description

For Pertactin the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥5 EU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

1.4

Notes
[8] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertactin ≥40 EU/mL

Statistical analysis description

For Pertactin the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥40 EU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

Difference

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

Notes
[9] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Hepatitis B ≥ 10.0 mIU/mL

Statistical analysis description

For hepatitis B the difference in percentages between the two groups (13vPnC – 7vPnC) at ≥10.0 mIU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.6

upper limit

Notes
[10] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Haemophilus influenzae type b at 0.15 μg/mL

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

Method

Parameter type

Difference

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.1

upper limit

2.4

Notes
[11] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Haemophilus influenzae type b at 1.0 μg/mL

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

Method

Parameter type

Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-8.2

upper limit

9.5

Notes
[12] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Diptheria at 0.01 IU/mL

Statistical analysis description

For Diptheria the difference in percentages between the two groups (13vPnC – 7vPnC) at 0.01 IU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

1.6

Notes
[13] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Diptheria at 0.1 IU/mL

Statistical analysis description

For Diptheria the difference in percentage between the two groups (13vPnC – 7vPnC) at 0.1 IU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

Method

Parameter type

Difference

Point estimate

-3.5

Confidence interval

level

95%

sides

2-sided

lower limit

-8.3

upper limit

0.8

Notes
[14] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Tetanus at 0.1 IU/mL

Statistical analysis description

For Tetanus the difference in percentage between the two groups (13vPnC – 7vPnC) at 0.1 IU/mL threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

Method

Parameter type

Difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.9

upper limit

7.1

Notes
[15] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Polio, Type 1 ≥1:8

Statistical analysis description

For Polio Type 1 the difference in percentage between the two groups (13vPnC – 7vPnC) at ≥1:8 threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

Method

Parameter type

Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

1.7

Notes
[16] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Polio, Type 2 ≥1:8

Statistical analysis description

For Polio Type 2 the difference in percentage between the two groups ( 13vPnC – 7vPnC) at ≥1:8 threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

Method

Parameter type

Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

2.8

Notes
[17] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Polio, Type 3 ≥1:8

Statistical analysis description

For Polio Type 3 the difference in percentages between the two groups (13vPnC – 7vPnC) at ≥1:8 threshold was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

Method

Parameter type

Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

2.9

Notes
[18] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis, PT ≥5 EU/mL

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.7

Notes
[19] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis FHA at ≥5 EU/mL

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.7

Notes
[20] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis PT ≥21 EU/mL

Statistical analysis description

For Pertussis PT the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥21 EU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

Method

Parameter type

Difference

Point estimate

-2.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.3

upper limit

1.8

Notes
[21] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis FHA at ≥7.82 EU/mL

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.7

Notes
[22] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertussis FHA ≥162 EU/mL

Statistical analysis description

For Pertussis FHA the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥162 EU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Parameter type

Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.3

upper limit

4.1

Notes
[23] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertactin ≥5 EU/mL

Statistical analysis description

For Pertactin the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥5 EU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

1.7

Notes
[24] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Pertactin ≥106 EU/mL

Statistical analysis description

For Pertactin the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥106 EU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

Parameter type

Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-4.7

upper limit

3.7

Notes
[25] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Hepatitis B ≥10.0 mIU/mL

Statistical analysis description

For hepatitis B the difference in percentages between the two groups (13vPnC - 7vPnC) at ≥10.0 mIU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

Parameter type

Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

Notes
[26] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Haemophilus influenzae type b at 0.15 μg/mL

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

Method

Parameter type

Difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

4.2

Notes
[27] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Haemophilus influenzae type b at 1.0 μg/mL

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

8.7

Notes
[28] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Diphtheria at 0.1 IU/mL

Statistical analysis description

For Diphtheria the difference in percentages between the two groups (13vPnC - 7vPnC) at 0.1 IU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Notes
[29] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Diphtheria at 0.01 IU/mL

Statistical analysis description

For Diphtheria the difference in percentages between the two groups (13vPnC - 7vPnC) at 0.01 IU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

Notes
[30] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Tetanus at 0.1 IU/mL

Statistical analysis description

For Tetanus the difference in percentages between the two groups (13vPnC - 7vPnC) at 0.1 IU/mL threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

Method

Parameter type

Difference

Point estimate

3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

10.9

Notes
[31] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Polio, Type 1 ≥1:8

Statistical analysis description

For Polio Type 1 the difference in percentage between the two groups (13vPnC - 7vPnC) at ≥1:8 threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.1

Notes
[32] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Polio, Type 2 ≥1:8

Statistical analysis description

For Polio Type 2 the difference in percentage between the two groups (13vPnC - 7vPnC) at ≥1:8 threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.1

Notes
[33] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Polio, Type 3 ≥1:8

Statistical analysis description

For Polio Type 3 the difference in percentage between the two groups (13vPnC - 7vPnC) at ≥1:8 threshold was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

Method

Parameter type

Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

2.1

Notes
[34] - Non-inferiority for concomitant antigens was declared if the lowest limit of the 2-sided 95% CI for the difference between the two groups was > -10%.

Primary: Geometric Mean Antibody Concentration (GMC) of Pertussis in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Top of page

End point title

Geometric Mean Antibody Concentration (GMC) of Pertussis in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

End point description

GMC of Pertussis (PT, FHA, PRN) were measured using an anti-Bordetella pertussis ELISA. Results were recorded in ELISA units per milliliter (EU/mL). Evaluable immunogenicity (per protocol) population adhered to the protocol requirements, had valid and determinate assay results, and had no other major protocol violations.

End point type

Primary

End point timeframe

One month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age)

End point values	13vPnC After 2-Dose Infant Series	7vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	275	279	254	261
Units: EU/mL
geometric mean (confidence interval 95%)
Pertussis FHA	102.87 (149.54 to 188.18)	105.17 (97.25 to 113.73)	463.23 (425.19 to 504.67)	456.55 (415.06 to 502.18)
Pertussis PT	50.01 (94.35 to 112.16)	48.44 (44.71 to 52.49)	60.89 (55.61 to 66.67)	64.53 (59.13 to 70.42)
Pertussis PRN	167.76 (45.82 to 54.58)	166.19 (150.28 to 183.78)	339.3 (309.16 to 372.38)	361.7 (328.59 to 398.14)

Pertussis PRN: After 2-Dose Infant Series

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

Method

Parameter type

Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.17

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

Pertussis PT: After 2-Dose Infant Series

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

Method

Parameter type

Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.16

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

Pertussis FHA: After 2-Dose Infant Series

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

Method

Parameter type

Ratio

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.1

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

Pertussis PRN: After Toddler dose

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

Method

Parameter type

Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.07

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

Pertussis PT: After Toddler dose

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[39]

Method

Parameter type

Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.07

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

Pertussis FHA: After Toddler dose

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

Method

Parameter type

Ratio

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

1.15

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

Primary: Geometric Mean Antibody Concentration (GMC) for Hepatitis B in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After Toddler Dose

Top of page

End point title

Geometric Mean Antibody Concentration (GMC) for Hepatitis B in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After Toddler Dose

End point description

GMC of anti-hepatitis B surface antigen (HBsAg) using an Food and Drug Administration (FDA) approved in vitro diagnostic kit. Evaluable immunogenicity (per protocol) population had valid and determinate assay results, and had no other major protocol violations.

End point type

Primary

End point timeframe

One month after the infant series (6 months of age) and the toddler dose (12 months of age)

End point values	13vPnC After 2-Dose Infant Series	7vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	273	276	252	255
Units: mIU/mL
geometric mean (confidence interval 95%)	260.46 (214.47 to 316.31)	272.67 (220.83 to 336.68)	1655.3 (1343.3 to 2039.77)	2284.95 (1878.82 to 2778.88)

Hepatitis b: After 2-Dose Infant Series

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

549

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

Method

Parameter type

Ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.27

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

Hepatitis b: After Toddler dose

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

507

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

Method

Parameter type

Ratio

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

0.96

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

Primary: Geometric Mean Antibody Concentration (GMC) of Haemophilus influenzae Type b (Hib) in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

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End point title

Geometric Mean Antibody Concentration (GMC) of Haemophilus influenzae Type b (Hib) in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

End point description

GMC for Hib polyribosylribitol phosphate as measured by ELISA, expressed in μg/mL. Evaluable immunogenicity (per protocol) population had valid and determinate assay results, and had no other major protocol violations.

End point type

Primary

End point timeframe

One month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age)

End point values	13vPnC After 2-Dose Infant Series	7vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	231	267	235	218
Units: μg/mL
geometric mean (confidence interval 95%)	0.99 (0.8 to 1.21)	1 (0.83 to 1.2)	9.09 (7.8 to 10.6)	8.85 (7.37 to 10.62)

Haemophilus influenzae b:After 2Dose Infant Series

Statistical analysis description

For Haemophilus influenzae type b the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

Method

Parameter type

Ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.3

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

Haemophilus influenzae b: After Toddler dose

Statistical analysis description

For Haemophilus influenzae type b the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

453

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

Method

Parameter type

Ratio

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.3

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

Primary: Geometric Mean Antibody Concentration (GMC) of Diptheria and Tetanus in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

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End point title

Geometric Mean Antibody Concentration (GMC) of Diptheria and Tetanus in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

End point description

GMC of anti-diphtheria and anti-tetanus toxoids as measured by ELISA (IU/mL). Evaluable immunogenicity (per protocol) population had valid and determinate assay results, and had no other major protocol violations; (n) = number of subjects with a determinate antibody concentration/titer for the specified concomitant antigen.

End point type

Primary

End point timeframe

One month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age)

End point values	13vPnC After 2-Dose Infant Series	7vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	275	279	254	261
Units: IU/mL
geometric mean (confidence interval 95%)
Diptheria (n=207,240,164,190)	0.52 (0.46 to 0.6)	0.67 (0.59 to 0.76)	2.77 (2.45 to 3.13)	3.71 (3.28 to 4.2)
Tetanus (n=155,214,125,96)	0.53 (0.45 to 0.63)	0.63 (0.53 to 0.74)	2.62 (2.12 to 3.25)	2.09 (1.56 to 2.81)

Diphtheria toxoid: After 2-Dose Infant Series

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

Method

Parameter type

Ratio

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

0.94

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

Diphtheria toxoid: After Toddler dose

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

Method

Parameter type

Ratio

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

0.89

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

Tetanus: After Toddler dose

Statistical analysis description

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

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

Method

Parameter type

Ratio

Point estimate

1.25

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

1.79

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

Tetanus: After 2-Dose Infant Series

Statistical analysis description

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

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

Method

Parameter type

Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.08

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

Primary: Geometric Mean Antibody Concentration (GMC) of Polio Types 1, 2, and 3 in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

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End point title

Geometric Mean Antibody Concentration (GMC) of Polio Types 1, 2, and 3 in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

End point description

GMC of Polio as measured using a polio in vitro plaque neutralization. Evaluable immunogenicity (per protocol) population had valid and determinate assay results, and had no other major protocol violations; (n) = number of subjects with a determinate antibody concentration/titer for the specified concomitant antigen.

End point type

Primary

End point timeframe

One month after infant series dose 2 (6 months of age) and after the toddler dose (12 months of age)

End point values	13vPnC After 2-Dose Infant Series	7vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	275	279	254	261
Units: Titers
geometric mean (confidence interval 95%)
Polio Type 1 (n=207,262,156,179)	180.72 (154.31 to 211.64)	207.17 (178.64 to 240.25)	924.52 (782.71 to 1092.03)	1348.04 (1163.56 to 1561.77)
Polio Type 2 (n=205,262,153,175)	123.74 (102.68 to 149.13)	130.39 (382.57 to 534.35)	1141.62 (958.68 to 1359.47)	1340.51 (1147.88 to 1565.48)
Polio Type 3 (n=205,262,153,178)	397.32 (327 to 482.76)	452.14 (109.96 to 154.63)	1567.64 (1289.72 to 1905.45)	2421.31 (2072.82 to 2828.39)

Polio Type 1: After 2-Dose Infant Series

Statistical analysis description

For Polio Type 1 the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

Method

Parameter type

Ratio

Point estimate

0.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.08

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

Polio Type 2: After 2-Dose Infant Series

Statistical analysis description

For Polio Type 2 the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

Method

Parameter type

Ratio

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.22

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

Polio Type 3: After 2-Dose Infant Series

Statistical analysis description

For Polio Type 3 the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After 2-Dose Infant Series v 7vPnC After 2-Dose Infant Series

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

Method

Parameter type

Ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.13

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

Polio Type 1: After Toddler dose

Statistical analysis description

For Polio Type 1 the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

Method

Parameter type

Ratio

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

0.86

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

Polio Type 2: After Toddler dose

Statistical analysis description

For Polio Type 2 the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

Method

Parameter type

Ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.07

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

Polio Type 3: After Toddler dose

Statistical analysis description

For Polio Type 3 the GMC ratio (13vPnC/7vPnC) was calculated.

Comparison groups

13vPnC After Toddler Dose v 7vPnC After Toddler Dose

Number of subjects included in analysis

515

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

Method

Parameter type

Ratio

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

0.83

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

Primary: Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Group After the 2-Dose Infant Series and Before the Toddler Dose

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End point title

Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Group After the 2-Dose Infant Series and Before the Toddler Dose ^[55]

End point description

Percentages of Subjects achieving World Health Organization (WHO) predefined antibody threshold ≥0.35 μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. The evaluable pneumococcal immunogenicity (per protocol) population was the primary analysis population consisting of eligible subjects who adhered to the protocol requirements, had valid and determinate assay results, and had no other major protocol violations.

End point type

Primary

End point timeframe

One month after infant series dose 2 (6 months of age) and before the toddler dose (11 months of age)

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

End point values	13vPnC After 2-Dose Infant Series	13vPnC Before Toddler Dose
Number of subjects analysed	265	246
Units: percentage of subjects
number (confidence interval 95%)
Common Serotypes - Serotype 4	96.6 (93.6 to 98.4)	66.9 (60.6 to 72.9)
Common Serotypes - Serotype 6B	58.4 (52.2 to 64.4)	76.3 (70.3 to 81.6)
Common Serotypes - Serotype 9V	94.7 (91.2 to 97.1)	70.5 (64.2 to 76.2)
Common Serotypes - Serotype 14	94.2 (90.6 to 96.7)	94.4 (90.6 to 97)
Common Serotypes - Serotype 18C	92.4 (88.5 to 95.3)	53 (46.4 to 59.5)
Common Serotypes - Serotype 19F	95.1 (91.7 to 97.3)	92.4 (88.2 to 95.4)
Common Serotypes - Serotype 23F	68.6 (62.6 to 74.1)	32.3 (26.4 to 38.7)
Additional Serotypes - Serotype 1	96.6 (93.6 to 98.4)	83.4 (78 to 87.9)
Additional Serotypes - Serotype 3	92.8 (89 to 95.6)	30.8 (24.9 to 37.1)
Additional Serotypes - Serotype 5	91.6 (87.5 to 94.6)	87.3 (82.4 to 91.3)
Additional Serotypes - Serotype 6A	86.5 (81.8 to 90.4)	86.4 (81.4 to 90.5)
Additional Serotypes - Serotype 7F	98.5 (96.2 to 99.6)	90.7 (86.3 to 94.1)
Additional Serotypes - Serotype 19A	98.5 (96.1 to 99.6)	96.2 (92.9 to 98.2)

No statistical analyses for this end point

Primary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Group After the 2-Dose Infant Series and Before Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Group After the 2-Dose Infant Series and Before Toddler Dose ^[56]

End point description

Antibody GMC 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. Evaluable pneumococcal immunogenicity (per protocol) population had valid and determinate assay results, and had no other major protocol violations.

End point type

Primary

End point timeframe

One month after infant series dose 2 (6 months of age) and before the toddler dose (11 months of age)

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

End point values	13vPnC After 2-Dose Infant Series	13vPnC Before Toddler Dose
Number of subjects analysed	265	246
Units: μg/mL
geometric mean (confidence interval 95%)
Common Serotypes - Serotype 4	2.38 (2.11 to 2.67)	0.53 (0.48 to 0.59)
Common Serotypes - Serotype 6B	0.41 (0.36 to 0.47)	0.61 (0.54 to 0.69)
Common Serotypes - Serotype 9V	1.68 (1.51 to 1.86)	0.48 (0.43 to 0.52)
Common Serotypes - Serotype 14	2.84 (2.44 to 3.31)	2.03 (1.79 to 2.3)
Common Serotypes - Serotype 18C	1.72 (1.54 to 1.93)	0.35 (0.32 to 0.39)
Common Serotypes - Serotype 19F	3.42 (2.95 to 3.97)	0.94 (0.83 to 1.06)
Common Serotypes - Serotype 23F	0.61 (0.53 to 0.71)	0.26 (0.23 to 0.29)
Additional Serotypes - Serotype 1	2.3 (2.03 to 2.6)	0.68 (0.61 to 0.75)
Additional Serotypes - Serotype 3	1.15 (1.04 to 1.28)	0.25 (0.22 to 0.27)
Additional Serotypes - Serotype 5	1.27 (1.14 to 1.41)	0.88 (0.8 to 0.97)
Additional Serotypes - Serotype 6A	1.17 (1.02 to 1.33)	0.81 (0.72 to 0.92)
Additional Serotypes - Serotype 7F	2.06 (1.88 to 2.26)	0.76 (0.7 to 0.82)
Additional Serotypes - Serotype 19A	2.87 (2.55 to 3.24)	1.2 (1.06 to 1.35)

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Relative to the 7vPnC Group After the Toddler Dose

Top of page

End point title

Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Relative to the 7vPnC Group After the Toddler Dose

End point description

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

End point type

Secondary

End point timeframe

One month after the toddler dose (12 months of age)

End point values	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	246	249
Units: percentage of subjects
number (confidence interval 95%)
Common Serotypes - Serotype 4 (n=244,245)	100 (98.5 to 100)	100 (98.5 to 100)
Common Serotypes - Serotype 6B (n=243,243)	100 (98.5 to 100)	100 (98.5 to 100)
Common Serotypes - Serotype 9V (n=235,248)	100 (98.4 to 100)	100 (98.5 to 100)
Common Serotypes - Serotype 14 (n=237,240)	99.6 (97.7 to 100)	99.6 (97.7 to 100)
Common Serotypes - Serotype 18C (n=245,247)	99.2 (97.1 to 99.9)	99.6 (97.8 to 100)
Common Serotypes - Serotype 19F (n=243,245)	98.8 (96.4 to 99.7)	98.4 (95.9 to 99.6)
Common Serotypes - Serotype 23F (n=240,243)	99.2 (97 to 99.9)	98.8 (96.4 to 99.7)
Additional Serotypes - Serotype 1 (n=244,240)	99.6 (97.7 to 100)	3.3 (1.4 to 6.5)
Additional Serotypes - Serotype 3 (n=245,240)	93.9 (90.1 to 96.5)	6.7 (3.9 to 10.6)
Additional Serotypes - Serotype 5 (n=245,218)	100 (98.5 to 100)	70.2 (63.6 to 76.2)
Additional Serotypes - Serotype 6A (n=243,243)	99.6 (97.7 to 100)	86.4 (81.5 to 90.5)
Additional Serotypes - Serotype 7F (n=242,243)	99.6 (97.7 to 100)	4.9 (2.6 to 8.5)
Additional Serotypes - Serotype 19A (n=241,241)	100 (98.5 to 100)	99.6 (97.7 to 100)

No statistical analyses for this end point

Secondary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Relative to 7vPnC Group After the Toddler Dose

Top of page

End point title

Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Relative to 7vPnC Group After the Toddler Dose

End point description

Antibody GMC 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. Evaluable pneumococcal immunogenicity (per protocol) had valid and determinate assay results, and had no other major protocol violations; (n) = number of subjects with a determinate antibody concentration for the specified serotype.

End point type

Secondary

End point timeframe

One month after toddler dose (12 months of age)

End point values	13vPnC After Toddler Dose	7vPnC After Toddler Dose
Number of subjects analysed	246	249
Units: μg/mL
geometric mean (confidence interval 95%)
Common Serotypes - Serotype 4 (n=244,245)	4.77 (4.29 to 5.3)	7.08 (6.41 to 7.83)
Common Serotypes - Serotype 6B (n=243,243)	10 (8.79 to 11.38)	10.39 (9.14 to 11.82)
Common Serotypes - Serotype 9V (n=235,248)	3.02 (2.74 to 3.32)	4.1 (3.72 to 4.51)
Common Serotypes - Serotype 14 (n=237,240)	10.3 (9.26 to 11.47)	11.99 (10.77 to 13.35)
Common Serotypes - Serotype 18C (n=245,247)	2.83 (2.55 to 3.14)	4.26 (3.85 to 4.7)
Common Serotypes - Serotype 19F (n=243,245)	9.01 (7.84 to 10.36)	8.06 (7.06 to 9.21)
Common Serotypes - Serotype 23F (n=240,243)	3.43 (3.02 to 3.88)	4.87 (4.3 to 5.51)
Additional Serotypes - Serotype 1 (n=244,240)	5.76 (5.12 to 6.47)	0.03 (0.03 to 0.04)
Additional Serotypes - Serotype 3 (n=245,240)	1.22 (1.09 to 1.35)	0.07 (0.06 to 0.08)
Additional Serotypes - Serotype 5 (n=245,218)	3.59 (3.25 to 3.96)	0.56 (0.49 to 0.64)
Additional Serotypes - Serotype 6A (n=243,243)	6.78 (6.04 to 7.61)	1.42 (1.21 to 1.66)
Additional Serotypes - Serotype 7F (n=242,243)	4.31 (3.94 to 4.72)	0.04 (0.04 to 0.05)
Additional Serotypes - Serotype 19A (n=241,241)	9.81 (8.82 to 10.92)	4.24 (3.85 to 4.67)

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

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End point title

Percentage of Subjects Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

End point description

Percentage of subjects achieving functional antibody titer ≥1:8 as measured by opsonophagocytic activity assay (OPA) along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented (This is not a geometric mean comparison as suggested by the table row heading). OPAs were done in a subset of approximately 100 subjects (range 90-100 per serotype) in the 13vPnC group.

End point type

Other pre-specified

End point timeframe

One month after infant series dose 2 and after the toddler dose

End point values	13vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose
Number of subjects analysed	100	100
Units: % Achieving OPA Titer ≥1:8
number (confidence interval 95%)
Common Serotypes - Serotype 4	100 (96.3 to 100)	100 (95.8 to 100)
Common Serotypes - Serotype 6B	90 (82.4 to 95.1)	99 (94.3 to 100)
Common Serotypes - Serotype 9V	100 (96.3 to 100)	100 (96.1 to 100)
Common Serotypes - Serotype 14	100 (96.3 to 100)	100 (96.2 to 100)
Common Serotypes - Serotype 18C	97 (91.4 to 99.4)	100 (96.3 to 100)
Common Serotypes - Serotype 19F	96 (90.1 to 98.9)	97.9 (92.7 to 99.7)
Common Serotypes - Serotype 23F	97 (91.4 to 99.4)	100 (96.3 to 100)
Additional Serotypes - Serotype 1	94.8 (88.3 to 98.3)	100 (96.2 to 100)
Additional Serotypes - Serotype 3	99 (94.6 to 100)	100 (96.2 to 100)
Additional Serotypes - Serotype 5	96 (90 to 98.9)	100 (96.1 to 100)
Additional Serotypes - Serotype 6A	95.9 (89.9 to 98.9)	100 (96.2 to 100)
Additional Serotypes - Serotype 7F	100 (96.4 to 100)	100 (96.2 to 100)
Additional Serotypes - Serotype 19A	95.6 (89 to 98.8)	100 (96 to 100)

No statistical analyses for this end point

Other pre-specified: Geometric Mean Antibody Titer (OPA) in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

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End point title

Geometric Mean Antibody Titer (OPA) in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

End point description

Antibody functionality/geometric mean titer (GMT) as measured by opsonophagocytic activity assay (OPA) 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. OPAs were done in a subset of approximately 100 subjects (range 90-100 per serotype) in the 13vPnC group.

End point type

Other pre-specified

End point timeframe

One month after infant series dose 2 and after the toddler dose

End point values	13vPnC After 2-Dose Infant Series	13vPnC After Toddler Dose
Number of subjects analysed	100	100
Units: Titers
geometric mean (confidence interval 95%)
Common Serotypes - Serotype 4	526.69 (431.88 to 642.32)	1276.21 (1025.09 to 1588.85)
Common Serotypes - Serotype 6B	191.34 (133.35 to 274.55)	2383.31 (1850.47 to 3069.57)
Common Serotypes - Serotype 9V	3585.8 (2787.34 to 4612.99)	16384 (13066.97 to 20543.06)
Common Serotypes - Serotype 14	1882.96 (1446.51 to 2451.1)	1903.89 (1580.9 to 2292.88)
Common Serotypes - Serotype 18C	294.48 (221.8 to 390.98)	1324.41 (1063.57 to 1649.22)
Common Serotypes - Serotype 19F	222.86 (170.46 to 291.37)	391.97 (296.34 to 518.46)
Common Serotypes - Serotype 23F	487.51 (356.25 to 667.13)	3679.67 (2971.61 to 4556.44)
Additional Serotypes - Serotype 1	62.63 (47.59 to 82.41)	294.07 (226.88 to 381.15)
Additional Serotypes - Serotype 3	176.07 (144.89 to 213.96)	504.66 (435.71 to 584.53)
Additional Serotypes - Serotype 5	127.11 (99.36 to 162.6)	333.24 (274.24 to 404.94)
Additional Serotypes - Serotype 6A	541.81 (392.09 to 748.68)	2217.29 (1821.95 to 2698.42)
Additional Serotypes - Serotype 7F	5914.33 (4710.83 to 7425.3)	14886.35 (12560.25 to 17643.22)
Additional Serotypes - Serotype 19A	157.59 (118.91 to 208.84)	1415.08 (1140.56 to 1755.66)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs were recorded from the signing of the Informed Consent Form (ICF) to 1 month after dose 2 and from toddler dose until toddler dose blood draw. All SAEs were recorded from the signing of the ICF to 6 months after the final study vaccination

Adverse event reporting additional description

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

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

0.0

Reporting group title

7vPnC Infant Series

Reporting group description

Subjects received one single 0.5mL dose of 7vPnC coadministered with Infanrix hexa at 3 and 5 months. Adverse events were collected from dose 1 to approximately one month after dose 2.

Reporting group title

13vPnC Infant Series

Reporting group description

Subjects received one single 0.5mL dose of 13vPnC coadministered with Infanrix hexa at 3 and 5 months. Adverse events were collected from dose 1 to approximately one month after dose 2.

Reporting group title

13vPnC Toddler Series

Reporting group description

Subjects received one single 0.5mL dose of 13vPnC coadministered with Infanrix hexa at 11 months of age. Adverse events were collected for approximately one month after toddler dose.

Reporting group title

7vPnC Toddler Series

Reporting group description

Subjects received one single 0.5mL dose of 7vPnC coadministered with Infanrix hexa at 11 months of age. Adverse events were collected for approximately one month after toddler dose.

Reporting group title

13vPnC After Infant Series

Reporting group description

Subjects received one single 0.5mL dose of 13vPnC coadministered with Infanrix hexa at 3 and 5 months. Adverse events (only any newly diagnosed chronic medical conditions) were collected from approximately one month after dose 2 to toddler dose.

Reporting group title

7vPnC After Infant Series

Reporting group description

Subjects received one single 0.5mL dose of 7vPnC coadministered with Infanrix hexa at 3 and 5 months. Adverse events (only any newly diagnosed chronic medical conditions) were collected from approximately one month after dose 2 to toddler dose.

Reporting group title

13vPnC 6-Month Follow-up

Reporting group description

Subjects received one single 0.5mL dose of 13vPnC coadministered with Infanrix hexa at 3 and 5 months (infant series) and 11 months of age (toddler dose). Adverse events (any newly diagnosed chronic medical conditions, hospitalizations, and SAEs) were collected for approximately six months after last visit.

Reporting group title

7vPnC 6-Month Follow-up

Reporting group description

Subjects received one single 0.5mL dose of 7vPnC coadministered with Infanrix hexa at 3 and 5 months (infant series) and 11 months of age (toddler dose). Adverse events (any newly diagnosed chronic medical conditions, hospitalizations, and SAEs) were collected for approximately six months after last visit.

Serious adverse events	7vPnC Infant Series	13vPnC Infant Series	13vPnC Toddler Series	7vPnC Toddler Series	13vPnC After Infant Series	7vPnC After Infant Series	13vPnC 6-Month Follow-up	7vPnC 6-Month Follow-up
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 302 (3.31%)	6 / 300 (2.00%)	3 / 284 (1.06%)	1 / 281 (0.36%)	8 / 299 (2.68%)	11 / 302 (3.64%)	9 / 299 (3.01%)	11 / 302 (3.64%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wheezing
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laryngospasm
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Crying
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Decreased activity
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Pelizaeus-Merzbacher disease
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrioventricular block complete
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Nervous system disorders
Depressed level of consciousness
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokinesia
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nystagmus
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	2 / 299 (0.67%)	0 / 302 (0.00%)	2 / 299 (0.67%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infantile spasms
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningism
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope vasovagal
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Microcytic anaemia
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Anal fissure
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	2 / 284 (0.70%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	1 / 281 (0.36%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Cough
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	3 / 302 (0.99%)	2 / 300 (0.67%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 302 (0.33%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	3 / 299 (1.00%)	2 / 302 (0.66%)	0 / 299 (0.00%)	4 / 302 (1.32%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 3	0 / 2	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear infection
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	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	0 / 0	0 / 0
Otitis media
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	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	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	2 / 302 (0.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kawasaki's disease
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis adenovirus
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	1 / 299 (0.33%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epstein-Barr virus infection
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Cellulitis orbital
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	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	0 / 0	0 / 0

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

Non-serious adverse events	7vPnC Infant Series	13vPnC Infant Series	13vPnC Toddler Series	7vPnC Toddler Series	13vPnC After Infant Series	7vPnC After Infant Series	13vPnC 6-Month Follow-up	7vPnC 6-Month Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	262 / 302 (86.75%)	271 / 300 (90.33%)	223 / 284 (78.52%)	230 / 281 (81.85%)	96 / 299 (32.11%)	90 / 302 (29.80%)	1 / 299 (0.33%)	0 / 302 (0.00%)
Surgical and medical procedures
Induration (Any) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	60 / 209 (28.71%)	51 / 207 (24.64%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	60	51	0	0	0	0	0	0
General disorders and administration site conditions
Irritability
subjects affected / exposed	2 / 302 (0.66%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	23 / 302 (7.62%)	24 / 300 (8.00%)	25 / 284 (8.80%)	16 / 281 (5.69%)	33 / 299 (11.04%)	34 / 302 (11.26%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	25	25	26	17	40	43	0	0
Injection site swelling
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Fever >39 degree C but <=40 degree C Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	11 / 233 (4.72%)	8 / 224 (3.57%)	16 / 167 (9.58%)	20 / 160 (12.50%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	11	8	16	20	0	0	0	0
Fever >=38 degree C but <=39 degree C Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	95 / 246 (38.62%)	103 / 247 (41.70%)	130 / 204 (63.73%)	103 / 197 (52.28%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	95	103	130	103	0	0	0	0
Fever >40 degree C Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	0 / 230 (0.00%)	0 / 222 (0.00%)	0 / 160 (0.00%)	1 / 152 (0.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Irritability Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	165 / 259 (63.71%)	188 / 258 (72.87%)	165 / 221 (74.66%)	170 / 227 (74.89%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	165	188	165	170	0	0	0	0
Decreased appetite Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	85 / 246 (34.55%)	87 / 246 (35.37%)	103 / 198 (52.02%)	113 / 197 (57.36%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	85	87	103	113	0	0	0	0
Increased sleep Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	178 / 276 (64.49%)	177 / 269 (65.80%)	105 / 195 (53.85%)	107 / 196 (54.59%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	178	177	105	107	0	0	0	0
Decreased sleep Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[8]	88 / 242 (36.36%)	96 / 244 (39.34%)	64 / 180 (35.56%)	61 / 171 (35.67%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	88	96	64	61	0	0	0	0
Fever >=38 degree C but <=39 degree C Dose 2 Infant Series
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[9]	137 / 226 (60.62%)	126 / 227 (55.51%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	137	126	0	0	0	0	0	0
Fever >39 degree C but <=40 degree C Dose 2 Infant Series
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[10]	14 / 201 (6.97%)	14 / 204 (6.86%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	14	14	0	0	0	0	0	0
Irritability Dose 2 Infant Series
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[11]	183 / 243 (75.31%)	185 / 245 (75.51%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	183	185	0	0	0	0	0	0
Decreased appetite Dose 2 Infant Series
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[12]	99 / 218 (45.41%)	104 / 220 (47.27%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	99	104	0	0	0	0	0	0
Increased sleep Dose 2 Infant Series
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[13]	131 / 232 (56.47%)	129 / 226 (57.08%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	131	129	0	0	0	0	0	0
Decreased sleep Dose 2 Infant Series
Additional description: Subjects affected and occurrences for SEs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Systemic Event 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[14]	89 / 213 (41.78%)	89 / 222 (40.09%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	89	89	0	0	0	0	0	0
Reproductive system and breast disorders
Genital rash
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	18 / 302 (5.96%)	18 / 300 (6.00%)	8 / 284 (2.82%)	7 / 281 (2.49%)	8 / 299 (2.68%)	7 / 302 (2.32%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	19	19	8	7	8	7	0	0
Asthma
subjects affected / exposed	0 / 302 (0.00%)	3 / 300 (1.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	3 / 299 (1.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	3	1	0	3	1	0	0
Rhonchi
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 302 (0.00%)	2 / 300 (0.67%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0
Pharyngolaryngeal pain
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0
Wheezing
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	1 / 299 (0.33%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	1	2	0	0
Psychiatric disorders
Sleep disorder
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Limb injury
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Cardiac disorders
Extrasystoles
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Nervous system disorders
Nystagmus
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	4 / 302 (1.32%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	4	0	1	0	1	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	12 / 302 (3.97%)	5 / 300 (1.67%)	8 / 284 (2.82%)	3 / 281 (1.07%)	2 / 299 (0.67%)	5 / 302 (1.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	14	5	8	3	2	5	0	0
Vomiting
subjects affected / exposed	5 / 302 (1.66%)	1 / 300 (0.33%)	4 / 284 (1.41%)	1 / 281 (0.36%)	1 / 299 (0.33%)	3 / 302 (0.99%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	5	1	4	1	1	3	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 302 (0.66%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	2 / 302 (0.66%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	2	0	0	1	0	1	0	0
Constipation
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	2 / 281 (0.71%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0
Flatulence
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Frequent bowel movements
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Haematochezia
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Gingival pain
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Perianal erythema
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Infantile colic
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	1 / 299 (0.33%)	3 / 302 (0.99%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	1	3	0	0
Nausea
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Regurgitation
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Hepatobiliary disorders
Hepatomegaly
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Dermatitis atopic
subjects affected / exposed	5 / 302 (1.66%)	3 / 300 (1.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)
occurrences all number	5	3	0	0	1	0	1	0
Eczema
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0
Rash
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	2 / 284 (0.70%)	1 / 281 (0.36%)	1 / 299 (0.33%)	2 / 302 (0.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	2	1	1	2	0	0
Skin fissures
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Skin lesion
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	2 / 302 (0.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	2	0	0
Tenderness (Any) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[15]	73 / 243 (30.04%)	75 / 234 (32.05%)	94 / 199 (47.24%)	83 / 188 (44.15%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	74	75	94	83	0	0	0	0
Tenderness (Significant) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[16]	8 / 231 (3.46%)	6 / 224 (2.68%)	14 / 164 (8.54%)	9 / 153 (5.88%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	8	6	14	9	0	0	0	0
Induration (Any) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[17]	47 / 240 (19.58%)	44 / 232 (18.97%)	50 / 175 (28.57%)	45 / 165 (27.27%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	47	44	50	45	0	0	0	0
Induration (Mild) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[18]	44 / 244 (18.03%)	41 / 232 (17.67%)	46 / 174 (26.44%)	35 / 161 (21.74%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	44	41	46	35	0	0	0	0
Induration (Moderate) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[19]	7 / 229 (3.06%)	8 / 223 (3.59%)	12 / 160 (7.50%)	16 / 157 (10.19%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	7	8	12	16	0	0	0	0
Erythema (Any) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[20]	65 / 245 (26.53%)	60 / 233 (25.75%)	65 / 178 (36.52%)	63 / 174 (36.21%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	65	60	65	63	0	0	0	0
Erythema (Mild) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[21]	60 / 244 (24.59%)	56 / 233 (24.03%)	58 / 178 (32.58%)	53 / 172 (30.81%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	60	56	58	53	0	0	0	0
Erythema (Moderate) Dose 1 Infant Series and Toddler Dose
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[22]	7 / 231 (3.03%)	6 / 222 (2.70%)	12 / 160 (7.50%)	17 / 156 (10.90%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	7	6	12	17	0	0	0	0
Tenderness (Significant) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[23]	10 / 199 (5.03%)	9 / 199 (4.52%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	10	9	0	0	0	0	0	0
Tenderness (Any) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[24]	79 / 215 (36.74%)	65 / 214 (30.37%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	79	65	0	0	0	0	0	0
Induration (Moderate) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[25]	10 / 195 (5.13%)	11 / 198 (5.56%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	10	11	0	0	0	0	0	0
Induration (Mild) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[26]	55 / 208 (26.44%)	45 / 207 (21.74%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	55	45	0	0	0	0	0	0
Erythema (Any) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[27]	73 / 212 (34.43%)	67 / 213 (31.46%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	73	67	0	0	0	0	0	0
Erythema (Mild) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[28]	68 / 211 (32.23%)	60 / 211 (28.44%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	68	60	0	0	0	0	0	0
Erythema (Moderate) Dose 2 Infant Series
Additional description: Subjects affected and occurrences for LRs is same as data collected through e-diaries cannot be used to distinguish one occurrence from another within a subject/vaccination. Version not captured, here 0.0 is mentioned for dictionary version.
alternative dictionary used: Local Reaction 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[29]	7 / 195 (3.59%)	11 / 200 (5.50%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	7	11	0	0	0	0	0	0
Renal and urinary disorders
Urinary tract pain
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Endocrine disorders
Thyroid cyst
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	10 / 302 (3.31%)	13 / 300 (4.33%)	4 / 284 (1.41%)	7 / 281 (2.49%)	8 / 299 (2.68%)	12 / 302 (3.97%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	10	13	4	8	9	14	0	0
Rhinitis
subjects affected / exposed	10 / 302 (3.31%)	11 / 300 (3.67%)	9 / 284 (3.17%)	5 / 281 (1.78%)	6 / 299 (2.01%)	4 / 302 (1.32%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	11	11	9	6	6	5	0	0
Bronchiolitis
subjects affected / exposed	9 / 302 (2.98%)	8 / 300 (2.67%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	9	8	0	0	1	0	0	0
Bronchitis
subjects affected / exposed	5 / 302 (1.66%)	6 / 300 (2.00%)	3 / 284 (1.06%)	1 / 281 (0.36%)	4 / 299 (1.34%)	8 / 302 (2.65%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	5	6	4	1	4	9	0	0
Pharyngitis
subjects affected / exposed	6 / 302 (1.99%)	8 / 300 (2.67%)	2 / 284 (0.70%)	11 / 281 (3.91%)	16 / 299 (5.35%)	7 / 302 (2.32%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	7	9	2	11	18	8	0	0
Gastroenteritis
subjects affected / exposed	4 / 302 (1.32%)	4 / 300 (1.33%)	5 / 284 (1.76%)	1 / 281 (0.36%)	4 / 299 (1.34%)	5 / 302 (1.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	4	4	5	1	4	5	0	0
Nasopharyngitis
subjects affected / exposed	6 / 302 (1.99%)	4 / 300 (1.33%)	1 / 284 (0.35%)	2 / 281 (0.71%)	0 / 299 (0.00%)	3 / 302 (0.99%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	6	5	1	2	0	3	0	0
Exanthema subitum
subjects affected / exposed	3 / 302 (0.99%)	4 / 300 (1.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	16 / 299 (5.35%)	22 / 302 (7.28%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	3	4	0	0	16	22	0	0
Ear infection
subjects affected / exposed	2 / 302 (0.66%)	4 / 300 (1.33%)	6 / 284 (2.11%)	7 / 281 (2.49%)	7 / 299 (2.34%)	7 / 302 (2.32%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	2	4	6	7	8	7	0	0
Influenza
subjects affected / exposed	5 / 302 (1.66%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	5	1	0	0	1	1	0	0
Varicella
subjects affected / exposed	3 / 302 (0.99%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	8 / 299 (2.68%)	5 / 302 (1.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	3	1	0	0	8	5	0	0
Urinary tract infection
subjects affected / exposed	2 / 302 (0.66%)	1 / 300 (0.33%)	0 / 284 (0.00%)	1 / 281 (0.36%)	3 / 299 (1.00%)	5 / 302 (1.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	3	1	0	1	4	6	0	0
Oral candidiasis
subjects affected / exposed	1 / 302 (0.33%)	1 / 300 (0.33%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0
Otitis media
subjects affected / exposed	2 / 302 (0.66%)	0 / 300 (0.00%)	2 / 284 (0.70%)	0 / 281 (0.00%)	1 / 299 (0.33%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	2	0	2	0	1	1	0	0
Sinusitis
subjects affected / exposed	1 / 302 (0.33%)	1 / 300 (0.33%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0
Viral skin infection
subjects affected / exposed	0 / 302 (0.00%)	2 / 300 (0.67%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0
Tracheitis
subjects affected / exposed	2 / 302 (0.66%)	0 / 300 (0.00%)	1 / 284 (0.35%)	1 / 281 (0.36%)	1 / 299 (0.33%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	2	0	1	1	1	1	0	0
Impetigo
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0
Otitis media acute
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	3 / 284 (1.06%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	3	0	1	0	0	0
Laryngitis
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	2 / 299 (0.67%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	1	3	0	0	0
Pharyngotonsillitis
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	1 / 284 (0.35%)	1 / 281 (0.36%)	3 / 299 (1.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	1	1	3	0	0	0
Tonsillitis
subjects affected / exposed	1 / 302 (0.33%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	2 / 299 (0.67%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	1	0	0	1	2	1	0	0
Enteritis infectious
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	2 / 302 (0.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	2 / 302 (0.66%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Erythema infectiosum
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0
Acute tonsillitis
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Bronchopneumonia
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	1 / 281 (0.36%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0
Cystitis
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	1 / 299 (0.33%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0
Roseola
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	0 / 284 (0.00%)	0 / 281 (0.00%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0
Herpes simplex
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0
Bronchospasm
subjects affected / exposed	3 / 302 (0.99%)	2 / 300 (0.67%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	1 / 302 (0.33%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	3	2	0	1	0	2	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 302 (0.00%)	1 / 300 (0.33%)	0 / 284 (0.00%)	1 / 281 (0.36%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0
Anorexia
subjects affected / exposed	0 / 302 (0.00%)	0 / 300 (0.00%)	1 / 284 (0.35%)	0 / 281 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)	0 / 299 (0.00%)	0 / 302 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0

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

More information

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Were there any global substantial amendments to the protocol? Yes

29 Mar 2007

Secondary objective was added to allow for an immunogenicity analysis of the 13vPnC and 7vPnC groups on serum samples collected after the toddler dose; the responses of 13vPnC relative to 7vPnC were to be measured. The statistics section was updated to state that the secondary endpoints for each of the pneumococcal serotypes were the proportion of subjects with a serotype specific IgG antibody concentration ≥0.35 μg/mL and the geometric mean IgG antibody concentration measured 1 month after the toddler dose.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A phase 3, randomized, Active-Controlled, Double-blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healhy Infants Given With Routine Pediatric Vaccination in Italy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Reporting Pre-Specified Local Reactions

Primary: Percentage of Subjects Reporting Pre-Specified Local Reactions

Primary: Percentage of Subjects Reporting Pre-Specified Systemic Events

Primary: Percentage of Subjects Reporting Pre-Specified Systemic Events

Primary: Percentage of Subjects Achieving Predefined Antibody Levels for Concomitant Antigen Pertussis, Hepatitis B, Haemophilus influenzae Type b, Diphtheria, Tetanus and Polio After the 2-Dose Infant Series and After the Toddler Dose

Primary: Percentage of Subjects Achieving Predefined Antibody Levels for Concomitant Antigen Pertussis, Hepatitis B, Haemophilus influenzae Type b, Diphtheria, Tetanus and Polio After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Pertussis in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Pertussis in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) for Hepatitis B in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) for Hepatitis B in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Haemophilus influenzae Type b (Hib) in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Haemophilus influenzae Type b (Hib) in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Diptheria and Tetanus in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Diptheria and Tetanus in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Polio Types 1, 2, and 3 in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Geometric Mean Antibody Concentration (GMC) of Polio Types 1, 2, and 3 in the 13vPnC Group Relative to the 7vPnC Group After the 2-Dose Infant Series and After the Toddler Dose

Primary: Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Group After the 2-Dose Infant Series and Before the Toddler Dose

Primary: Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Group After the 2-Dose Infant Series and Before the Toddler Dose

Primary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Group After the 2-Dose Infant Series and Before Toddler Dose

Primary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Group After the 2-Dose Infant Series and Before Toddler Dose

Secondary: Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Relative to the 7vPnC Group After the Toddler Dose

Secondary: Percentage of Subjects Achieving an Antibody Level of ≥0.35 μg/mL in the 13vPnC Relative to the 7vPnC Group After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Relative to 7vPnC Group After the Toddler Dose

Secondary: Geometric Mean Concentration (GMC) for Serotype-specific Pneumococcal Immunoglobulin G (IgG) Antibody in 13vPnC Relative to 7vPnC Group After the Toddler Dose

Other pre-specified: Percentage of Subjects Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

Other pre-specified: Percentage of Subjects Achieving Antibody Titer (OPA) ≥1:8 in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

Other pre-specified: Geometric Mean Antibody Titer (OPA) in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

Other pre-specified: Geometric Mean Antibody Titer (OPA) in 13vPnC Group After the 2-Dose Infant Series and the Toddler Dose

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A phase 3, randomized, Active-Controlled, Double-blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine in Healhy Infants Given With Routine Pediatric Vaccination in Italy