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Clinical Trial Results:
A Phase 3, Open Label Trial Evaluating the Safety, Immunogenicity and Impact of 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children.

Summary
EudraCT number	2008-003648-12
Trial protocol	Outside EU/EEA
Global end of trial date	10 Sep 2010

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

6096A1-3010 (B1851009)

ISRCTN number

US NCT number

NCT00743652

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

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

Public contact

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

Scientific contact

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

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

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

17 Oct 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Sep 2010

Was the trial ended prematurely?

Main objective of the trial

To assess the impact of 13vPnC on the incidence of invasive pneumococcal disease (IPD) in the Yukon Kuskokwim (YK) Delta region due to the 13 vaccine Streptococcus (S.) pneumoniae serotypes.

Protection of trial subjects

This study was conducted in accordance with the International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP) and the ethical principles that have their origins in the Declaration of Helsinki. Written informed consent was obtained from all parent(s)/legal guardian(s) of every subject before enrollment in the study and before performance of any study-related procedures.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Jan 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 373

Worldwide total number of subjects

373

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

294

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

Blood sample was optional for subjects living in the Bethel area. Active vaccination stopped when 13vPnC was commercially available in Alaska. Study ended after a 6-month follow-up for safety following the last vaccination.

Screening details

Total 373 subjects were enrolled in 24 centres of United States. Study started on 30 Jan 2009 and completed on 10 Sep 2010.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)

Arm description

Subjects 6 weeks to less than (<) 10 months of age with 0 prior doses of Prevnar received 3 doses of 13-valent pneumococcal conjugate vaccine (13vPnC) at least 28 days apart (infant series) and a single dose of 13vPnC at greater than (>) 12 months of age (toddler dose), at least 60 days after last infant dose.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects 6 weeks to < 10 months of age with 0 prior doses of Prevnar received 3 single intramuscular (IM) 0.5 milliliter (mL) doses of 13vPnC at least 28 days apart (infant series), and a single IM 0.5 mL dose of 13vPnC at > 12 months of age (toddler dose), at least 60 days after last infant dose.

13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)

Arm description

Subjects <12 months of age with 1 prior dose of Prevnar received 2 doses of 13vPnC at least 28 days apart (infant series), and a single dose of 13vPnC at >12 months of age (toddler dose), at least 60 days after last infant dose.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects <12 months of age with 1 prior dose of Prevnar received 2 single IM 0.5 mL doses of 13vPnC at least 28 days apart (infant series), and a single IM 0.5 mL dose of 13vPnC at >12 months of age (toddler dose), at least 60 days after last infant dose.

13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)

Arm description

Subjects <12 months of age with 2 prior doses of Prevnar received a single dose of 13vPnC (infant series) and a single dose of 13vPnC at >12 months of age (toddler dose), at least 60 days after last infant dose.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects <12 months of age with 2 prior doses of Prevnar received a single IM 0.5 mL dose of 13vPnC (infant series) and a single IM 0.5 mL dose of 13vPnC at >12 months of age (toddler dose), at least 60 days after last infant dose.

13vPnC Group 4 (2 Catch-Up Doses)

Arm description

Subjects greater than or equal to (≥) 12 months to <2 years of age received 2 single doses of 13vPnC at least 60 days apart.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects ≥ 12 months to <2 years of age received 2 single IM 0.5 mL doses of 13vPnC at least 60 days apart.

13vPnC Group 5 (1 Catch-Up Dose)

Arm description

Subjects ≥2 years to <5 years of age received a single dose of 13vPnC.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects ≥2 years to <5 years of age received a single IM 0.5 mL dose of 13vPnC.

Number of subjects in period 1	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Started	151	51	25	67	79
Vaccinated Dose 1	151	51	25	66	79
Vaccinated Dose 2	112 ^[1]	41 ^[2]	0 ^[3]	49 ^[4]	0 ^[5]
Vaccinated Dose 3	74 ^[6]	0 ^[7]	0 ^[8]	0 ^[9]	0 ^[10]
Toddler Dose	15 ^[11]	23 ^[12]	16 ^[13]	0 ^[14]	0 ^[15]
Completed	141	48	23	63	79
Not completed	10	3	2	4	0
'Parent/Legal Guardian Request '	3	2	2	2	-
'Adverse Event '	3	-	-	-	-
Death	2	-	-	-	-
Unspecified	1	1	-	-	-
Lost to follow-up	1	-	-	-	-
'Investigator Request '	-	-	-	2	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 4 were not administered with Vaccination Dose 3 and Toddler dose.
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 5 were not administered with Vaccination Dose 2, Vaccination Dose 3 and Toddler dose.
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[7] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[8] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 3 were not administered with Vaccination Dose 2 and Vaccination Dose 3.
[9] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 4 were not administered with Vaccination Dose 3 and Toddler dose.
[10] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 5 were not administered with Vaccination Dose 2, Vaccination Dose 3 and Toddler dose.
[11] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[12] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[13] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who completed the study were not administered with all vaccinations.
[14] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 4 were not administered with Vaccination Dose 3 and Toddler dose.
[15] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects of 13vPnC Group 5 were not administered with Vaccination Dose 2, Vaccination Dose 3 and Toddler dose.

Baseline characteristics

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Reporting group title

13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)

Reporting group description

Reporting group title

13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)

Reporting group description

Reporting group title

13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)

Reporting group description

Reporting group title

13vPnC Group 4 (2 Catch-Up Doses)

Reporting group description

Subjects greater than or equal to (≥) 12 months to <2 years of age received 2 single doses of 13vPnC at least 60 days apart.

Reporting group title

13vPnC Group 5 (1 Catch-Up Dose)

Reporting group description

Subjects ≥2 years to <5 years of age received a single dose of 13vPnC.

Reporting group values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)	Total
Number of subjects	151	51	25	67	79	373
Age categorical
Units: Subjects
Age continuous
Units: months
arithmetic mean (standard deviation)	1.4 ( 0.6 )	4.4 ( 0.8 )	7.1 ( 1.6 )	15.2 ( 3.4 )	40.1 ( 11.1 )	-
Gender categorical
Units: Subjects
Female	73	23	11	36	47	190
Male	78	28	14	31	32	183

End points

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Reporting group title

13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)

Reporting group description

Reporting group title

13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)

Reporting group description

Reporting group title

13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)

Reporting group description

Reporting group title

13vPnC Group 4 (2 Catch-Up Doses)

Reporting group description

Subjects greater than or equal to (≥) 12 months to <2 years of age received 2 single doses of 13vPnC at least 60 days apart.

Reporting group title

13vPnC Group 5 (1 Catch-Up Dose)

Reporting group description

Subjects ≥2 years to <5 years of age received a single dose of 13vPnC.

Subject analysis set title

13vPnC (All Subjects)

Subject analysis set type

Safety analysis

Subject analysis set description

Safety population.

Primary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series

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End point title

Percentage of Subjects Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series ^[1] ^[2]

End point description

Percentage of subjects in 13vPnC Groups 1, 2 and 3 achieving predefined antibody threshold ≥0.35 mcg/mL along with the corresponding 95% confidence interval (CI) for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population: received treatments as randomized at all expected doses, blood drawn within specified timeframes, at least 1 valid and determinate assay result for proposed analysis, and no major protocol violations.

End point type

Primary

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3.

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.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11 ^[3]	6 ^[4]	3 ^[5]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotypes - serotype 6B	100 (71.5 to 100)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Common serotypes - serotype 9V	100 (71.5 to 100)	83.3 (35.9 to 99.6)	100 (29.2 to 100)
Common serotypes - serotype 14	90.9 (58.7 to 99.8)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 18C	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotype - serotype 19F	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotype - serotype 23F	90.9 (58.7 to 99.8)	83.3 (35.9 to 99.6)	100 (29.2 to 100)
Additional serotype - serotype 1	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 3	90.9 (58.7 to 99.8)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 5	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 6A	90.9 (58.7 to 99.8)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 7F	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 19A	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)

Notes
[3] - Number of subjects with a determinate IgG antibody concentration to the given serotype.
[4] - Number of subjects with a determinate IgG antibody concentration to the given serotype.
[5] - Number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Toddler Dose

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End point title

Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Toddler Dose ^[6] ^[7]

End point description

Percentage of subjects in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥0.35 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population.

End point type

Primary

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3.

Notes
[6] - 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.
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2 ^[8]	6 ^[9]	2 ^[10]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 6B	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 9V	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 14	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 18C	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 19F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 23F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 1	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 3	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 5	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 6A	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 7F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 19A	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)

Notes
[8] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[9] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[10] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Relevant Catch-Up Dose

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End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Relevant Catch-Up Dose ^[11] ^[12]

End point description

Percentage of subjects in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥0.35 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population.

End point type

Primary

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5.

Notes
[11] - 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.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[13]	9 ^[14]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 6B	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 9V	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 14	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 18C	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 19F	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 23F	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 1	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 3	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 5	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 6A	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 7F	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 19A	100 (39.8 to 100)	100 (66.4 to 100)

Notes
[13] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[14] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Primary: Number of Cases of Invasive Pneumococcal Disease (IPD) in Subjects Less Than 5 Years of Age Due to Any Serotype Contained in 13vPnC

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End point title

Number of Cases of Invasive Pneumococcal Disease (IPD) in Subjects Less Than 5 Years of Age Due to Any Serotype Contained in 13vPnC ^[15]

End point description

In order to assess the impact of 13vPnC on the incidence of IPD in the YK Delta region, the Centers for Disease Control and Prevention (CDC) Arctic Investigation Program (AIP) accessed IPD data through evaluation of ongoing statewide IPD surveillance in Alaska. The CDC’s AIP followed IPD (including serotype and vaccination history) to show whether identified cases of IPD received Prevnar, 13vPnC, or both. These data were combined with statewide data and used to identify the overall trend in IPD in the YK Delta region after introduction of 13vPnC. Safety population.

End point type

Primary

End point timeframe

Baseline to 6 months after last vaccination

Notes
[15] - 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 end point.

End point values	13vPnC (All Subjects)
Number of subjects analysed	373
Units: Subjects
number (not applicable)	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Serum IgG Antibody Level ≥0.35 Mcg/mL Prior to Vaccination With 13vPnC (Groups 4 and 5 Only)

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End point title

Percentage of Subjects Achieving Serum IgG Antibody Level ≥0.35 Mcg/mL Prior to Vaccination With 13vPnC (Groups 4 and 5 Only) ^[16]

End point description

End point type

Secondary

End point timeframe

28 to 56 days before vaccination 2 for Group 4, and before the single vaccination in Group 5.

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[17]	9 ^[18]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	50 (6.8 to 93.2)	50 (15.7 to 84.3)
Common serotypes - serotype 6B	100 (39.8 to 100)	88.9 (51.8 to 99.7)
Common serotypes - serotype 9V	100 (39.8 to 100)	66.7 (29.9 to 92.5)
Common serotypes - serotype 14	100 (29.2 to 100)	88.9 (51.8 to 99.7)
Common serotype - serotype 18C	75 (19.4 to 99.4)	33.3 (7.5 to 70.1)
Common serotype - serotype 19F	100 (39.8 to 100)	88.9 (51.8 to 99.7)
Common serotype - serotype 23F	100 (39.8 to 100)	88.9 (51.8 to 99.7)
Additional serotype - serotype 1	0 (0 to 60.2)	12.5 (0.3 to 52.7)
Additional serotype - serotype 3	0 (0 to 60.2)	37.5 (8.5 to 75.5)
Additional serotype - serotype 5	50 (6.8 to 93.2)	100 (66.4 to 100)
Additional serotype - serotype 6A	100 (39.8 to 100)	88.9 (51.8 to 99.7)
Additional serotype - serotype 7F	0 (0 to 60.2)	33.3 (7.5 to 70.1)
Additional serotype - serotype 19A	100 (39.8 to 100)	88.9 (51.8 to 99.7)

Notes
[17] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[18] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Infant Series

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End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Infant Series ^[19]

End point description

Percentage of subjects in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥1.0 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population.

End point type

Secondary

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3.

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11 ^[20]	6 ^[21]	3 ^[22]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	90.9 (58.7 to 99.8)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotypes - serotype 6B	72.7 (39 to 94)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Common serotypes - serotype 9V	81.8 (48.2 to 97.7)	66.7 (22.3 to 95.7)	66.7 (9.4 to 99.2)
Common serotypes - serotype 14	90.9 (58.7 to 99.8)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Common serotype - serotype 18C	63.6 (30.8 to 89.1)	83.3 (35.9 to 99.6)	100 (29.2 to 100)
Common serotype - serotype 19F	100 (71.5 to 100)	66.7 (22.3 to 95.7)	100 (29.2 to 100)
Common serotype - serotype 23F	63.6 (30.8 to 89.1)	50 (11.8 to 88.2)	100 (29.2 to 100)
Additional serotype - serotype 1	81.8 (48.2 to 97.7)	83.3 (35.9 to 99.6)	100 (29.2 to 100)
Additional serotype - serotype 3	54.5 (23.4 to 83.3)	66.7 (22.3 to 95.7)	100 (29.2 to 100)
Additional serotype - serotype 5	81.8 (48.2 to 97.7)	83.3 (35.9 to 99.6)	66.7 (9.4 to 99.2)
Additional serotype - serotype 6A	72.7 (39 to 94)	83.3 (35.9 to 99.6)	66.7 (9.4 to 99.2)
Additional serotype - serotype 7F	100 (71.5 to 100)	83.3 (35.9 to 99.6)	100 (29.2 to 100)
Additional serotype - serotype 19A	72.7 (39 to 100)	50 (11.8 to 88.2)	33.3 (0.8 to 90.6)

Notes
[20] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[21] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[22] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Toddler Dose

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End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Toddler Dose ^[23]

End point description

End point type

Secondary

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2 ^[24]	6 ^[25]	2 ^[26]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (15.8 to 100)	100 (54.1 to 100)	50 (1.3 to 98.7)
Common serotypes - serotype 6B	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 9V	100 (15.8 to 100)	100 (54.1 to 100)	50 (1.3 to 98.7)
Common serotypes - serotype 14	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 18C	100 (15.8 to 100)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Common serotype - serotype 19F	100 (15.8 to 100)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Common serotype - serotype 23F	100 (15.8 to 100)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Additional serotype - serotype 1	100 (15.8 to 100)	83.3 (35.9 to 99.6)	100 (15.8 to 100)
Additional serotype - serotype 3	50 (1.3 to 98.7)	66.7 (22.3 to 95.7)	100 (15.8 to 100)
Additional serotype - serotype 5	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 6A	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 7F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 19A	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)

Notes
[24] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[25] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[26] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Relevant Catch-up Dose

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End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Relevant Catch-up Dose ^[27]

End point description

Percentage of subjects in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥1.0 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population.

End point type

Secondary

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[28]	9 ^[29]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 6B	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 9V	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 14	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 18C	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 19F	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 23F	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 1	100 (39.8 to 100)	66.7 (29.9 to 92.5)
Additional serotype - serotype 3	100 (39.8 to 100)	77.8 (40 to 97.2)
Additional serotype - serotype 5	100 (39.8 to 100)	88.9 (51.8 to 99.7)
Additional serotype - serotype 6A	100 (39.8 to 100)	88.9 (51.8 to 99.7)
Additional serotype - serotype 7F	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 19A	100 (39.8 to 100)	100 (66.4 to 100)

Notes
[28] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[29] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 1

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End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 1 ^[30]

End point description

Local reactions were reported by the parent/legal guardian using a diary card. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may have been represented in more than 1 category. Safety Population: all subjects who received at least 1 dose of 13vPnC; n=number of subjects with specific characteristics.

End point type

Secondary

End point timeframe

Day 1 through Day 7 after vaccination 1 for Group 4 and after the single vaccination in Group 5.

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	65 ^[31]	77 ^[32]
Units: Percentage of Subjects
number (not applicable)
Tenderness: Any (n=65,77)	32.3	48.1
Tenderness: Significant (n=63,77)	3.2	9.1
Swelling: Any (n=64,77)	7.8	7.8
Swelling: Mild (n=62,76)	3.2	2.6
Swelling: Moderate (n=63,77)	3.2	6.5
Swelling: Severe (n=63,77)	1.6	2.6
Redness: Any (n=65,77)	15.4	13
Redness: Mild (n=63,77)	11.1	11.7
Redness: Moderate (n=64,77)	4.7	5.2
Redness: Severe (n=63,77)	1.6	2.6

Notes
[31] - N=number of subjects reporting yes for at least 1 day or no for all days.
[32] - N=number of subjects reporting yes for at least 1 day or no for all days.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 2

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End point title

Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 2 ^[33]

End point description

Local reactions were reported by the parent/legal guardian using a diary card. Tenderness was scaled as Any (tenderness present); Significant (present and interfered with limb movement). Redness and swelling were scaled as Any (redness or swelling present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (2.5 to 7.0 cm); Severe (> 7.0 cm). Subjects may have been represented in more than 1 category. Safety Population; n=number of subjects with specific characteristics.

End point type

Secondary

End point timeframe

Day 1 through Day 7 after vaccination 2 for Group 4

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)
Number of subjects analysed	49 ^[34]
Units: Percentage of Subjects
number (not applicable)
Tenderness: Any (n=49)	36.7
Tenderness: Significant (n=49)	10.2
Swelling: Any (n=48)	10.4
Swelling: Mild (n=47)	8.5
Swelling: Moderate (n=47)	0
Swelling: Severe (n=47)	0
Redness: Any (n=49)	6.1
Redness: Mild (n=48)	4.2
Redness: Moderate (n=48)	0
Redness: Severe (n=48)	0

Notes
[34] - N=number of subjects reporting yes for at least 1 day or no for all days.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 1

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End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 1 ^[35]

End point description

Systemic events (any fever 38 degrees Celsius [C] or higher, decreased appetite, irritability, increased sleep, decreased sleep, hives [urticaria], and use of antipyretic medication) were reported using a diary card. Subjects may have been represented in more than 1 category. Subjects may have been represented in more than 1 category. Safety Population, n=number of subjects with specific characteristics.

End point type

Secondary

End point timeframe

Day 1 through Day 7 after vaccination 1 for Group 4 and after the single vaccination in Group 5

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	66 ^[36]	77 ^[37]
Units: Percentage of Subjects
number (not applicable)
Fever ≥38 degrees C but ≤39 degrees C (n=35,47)	42.9	27.7
Fever >39 degrees C but ≤40 degrees C (n=29,43)	20.7	11.6
Fever >40 degrees C (n=28,40)	7.1	0
Decreased appetite (n=66,77)	31.8	24.7
Irritability (n=66,77)	53	41.6
Increased sleep (n=66,77)	33.3	22.1
Decreased sleep (n=66,77)	24.2	11.7
Hives (urticaria) (n=66,77)	3	2.6

Notes
[36] - N=number of subjects reporting yes for at least 1 day or no for all days.
[37] - N=number of subjects reporting yes for at least 1 day or no for all days.

No statistical analyses for this end point

Secondary: Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 2

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End point title

Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 2 ^[38]

End point description

Systemic events (any fever 38 degrees C or higher, decreased appetite, irritability, increased sleep, decreased sleep, hives [urticaria], and use of antipyretic medication) were reported using a diary card. Subjects may have been represented in more than 1 category. Safety Population; n=number of subjects with specific characteristics.

End point type

Secondary

End point timeframe

Day 1 through Day 7 after vaccination 2 for Group 4

Notes
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)
Number of subjects analysed	49 ^[39]
Units: Percentage of Subjects
number (not applicable)
Fever ≥38 degrees C but ≤39 degrees C (n=26)	23.1
Fever >39 degrees C but ≤40 degrees C (n=22)	9.1
Fever >40 degrees C (n=21)	0
Decreased appetite (n=49)	22.4
Irritability (n=49)	57.1
Increased sleep (n=49)	26.5
Decreased sleep (n=49)	4.1
Hives (urticaria) (n=49)	2

Notes
[39] - N=number of subjects reporting yes for at least 1 day or no for all days.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Infant Series

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End point title

Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Infant Series ^[40]

End point description

Percentage of subjects in 13vPnC Groups 1, 2, and 3 achieving predefined antibody threshold ≥0.15 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3

Notes
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11 ^[41]	6 ^[42]	3 ^[43]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotypes - serotype 6B	100 (71.5 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 9V	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotypes - serotype 14	90.9 (58.7 to 99.8)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 18C	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotype - serotype 19F	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Common serotype - serotype 23F	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 1	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 3	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 5	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 6A	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 7F	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)
Additional serotype - serotype 19A	100 (71.5 to 100)	100 (54.1 to 100)	100 (29.2 to 100)

Notes
[41] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[42] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[43] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Toddler Dose

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End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Toddler Dose ^[44]

End point description

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3.

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2 ^[45]	6 ^[46]	2 ^[47]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 6B	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 9V	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotypes - serotype 14	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 18C	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 19F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Common serotype - serotype 23F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 1	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 3	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 5	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 6A	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 7F	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)
Additional serotype - serotype 19A	100 (15.8 to 100)	100 (54.1 to 100)	100 (15.8 to 100)

Notes
[45] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[46] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[47] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Relevant Catch-up Dose

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End point title

Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Relevant Catch-up Dose ^[48]

End point description

Percentage of subjects in 13vPnC Groups 4 and 5 achieving predefined antibody threshold ≥0.15 mcg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented. Exact 2-sided CI based upon the observed proportion of subjects. Evaluable immunogenicity population.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5

Notes
[48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[49]	9 ^[50]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 6B	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 9V	100 (39.8 to 100)	100 (66.4 to 100)
Common serotypes - serotype 14	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 18C	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 19F	100 (39.8 to 100)	100 (66.4 to 100)
Common serotype - serotype 23F	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 1	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 3	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 5	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 6A	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 7F	100 (39.8 to 100)	100 (66.4 to 100)
Additional serotype - serotype 19A	100 (39.8 to 100)	100 (66.4 to 100)

Notes
[49] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[50] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Infant Series

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End point title

Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Infant Series ^[51]

End point description

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3

Notes
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11 ^[52]	6 ^[53]	3 ^[54]
Units: Microgram/milliliter (mcg/mL)
geometric mean (confidence interval 95%)
Common serotypes - serotype 4	2.64 (1.55 to 4.49)	2.11 (0.93 to 4.8)	4.27 (0.49 to 37.05)
Common serotypes - serotype 6B	2.74 (1.23 to 6.12)	2.59 (0.55 to 12.26)	28.6 (0.12 to 7043.76)
Common serotypes - 9V	1.38 (0.97 to 1.98)	1.04 (0.46 to 2.38)	1.6 (0.31 to 8.37)
Common serotypes - serotype 14	4.78 (1.71 to 13.33)	4.08 (1.68 to 9.88)	10.73 (0.06 to 1894.14)
Common serotypes - serotype 18C	1.83 (1.04 to 3.21)	1.66 (0.92 to 2.98)	2.99 (0.4 to 22.62)
Common serotypes - serotype 19F	3.55 (2.1 to 6.01)	1.61 (0.65 to 4.01)	2.37 (1.43 to 3.93)
Common serotypes - serotype 23F	1.54 (0.79 to 3.01)	1.03 (0.35 to 3.04)	3.37 (1.18 to 9.66)
Additional serotype - serotype 1	3.33 (1.68 to 6.62)	3.02 (1.06 to 8.6)	2.87 (0.3 to 27.24)
Additional serotype - serotype 3	0.79 (0.51 to 1.22)	1.61 (0.62 to 4.16)	5.07 (1.53 to 16.79)
Additional serotype - serotype 5	2.89 (1.57 to 5.31)	1.93 (1.14 to 3.26)	1.75 (0.25 to 12.25)
Additional serotype - serotype 6A	2.19 (0.93 to 5.16)	2.48 (0.91 to 6.78)	5.41 (0.01 to 2495.5)
Additional serotype - serotype 7F	3.34 (1.99 to 5.61)	3.18 (1.24 to 8.12)	6.21 (1.84 to 20.92)
Additional serotype - serotype 19A	1.87 (1.11 to 3.17)	1.35 (0.56 to 3.25)	0.97 (0.37 to 2.53)

Notes
[52] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[53] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[54] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Other pre-specified: GMC for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Toddler Dose

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End point title

GMC for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Toddler Dose ^[55]

End point description

Antibody GMCs (mcg/mL) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A). GMC (13vPnC) with 2-sided 95% CIs were evaluated. CIs are back transformations of confidence levels based on Student t distribution for mean logarithm of concentrations. GMCs were calculated using all subjects with available data for specified blood draw. Evaluable immunogenicity population. Here "99999" in the 95% CI signifies not available (NA). For reporting group 13vPnC Group 1, in serotype common 6B NA = 3.929*10^11 and in additional serotype 6A NA = 6.518*10^11. For reporting group 13vPnC Group 3, NA signifies that n=2 for this serotype and the value for both subject was 3.96, thus there was no variability so 95% CI could not be determined.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, after vaccination 2 for Group 3

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2 ^[56]	6 ^[57]	2 ^[58]
Units: mcg/mL
geometric mean (confidence interval 95%)
Common serotypes - serotype 4	7.16 (0 to 199911.7)	2.55 (1.44 to 4.53)	1.76 (0 to 4004.84)
Common serotypes - serotype 6B	13.64 (0 to 99999)	12.01 (4.23 to 34.08)	11.32 (0.01 to 11544.32)
Common serotypes - serotype 9V	2.17 (0.01 to 373.79)	2.2 (1.3 to 3.73)	1.3 (0 to 2387.89)
Common serotypes - serotype 14	12.18 (0.06 to 2411.14)	11.42 (5.9 to 22.12)	8.54 (0.19 to 377.53)
Common serotype - serotype 18C	2.35 (0 to 1681.49)	2.22 (1.22 to 4.03)	2.42 (0.08 to 72.55)
Common serotype - serotype 19F	11 (0 to 11762036)	2.84 (1.03 to 7.79)	3.65 (0 to 130178.5)
Common serotype - serotype 23F	3.79 (0 to 66245120)	2.35 (0.88 to 6.27)	3.96 (-99999 to 99999)
Additional serotype - serotype 1	2.15 (0 to 9338.28)	4.19 (1.46 to 12.02)	16.7 (0 to 5685164)
Additional serotype - serotype 3	0.73 (0 to 276.18)	1.32 (0.63 to 2.78)	1.63 (1.19 to 2.23)
Additional serotype - serotype 5	4.69 (0 to 36146.55)	3.56 (1.96 to 6.46)	5.85 (0.02 to 1606.11)
Additional serotype - serotype 6A	17.14 (0 to 99999)	7.79 (3 to 20.21)	3.24 (0.01 to 1555.15)
Additional serotype - serotype 7F	7.45 (0.47 to 117.4)	5.55 (2.59 to 11.87)	4.5 (0.05 to 440.58)
Additional serotype - serotype 19A	10.53 (2.63 to 42.07)	3.21 (1.23 to 8.39)	8.86 (0 to 8014211)

Notes
[56] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[57] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.
[58] - N=number of subjects with a determinate IgG antibody concentration to the given serotype.

No statistical analyses for this end point

Other pre-specified: GMC for Serotype-specific Pneumococcal IgG Antibodies 1 Month After the Relevant Catch-up Dose

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End point title

GMC for Serotype-specific Pneumococcal IgG Antibodies 1 Month After the Relevant Catch-up Dose ^[59]

End point description

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5.

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[60]	9 ^[61]
Units: mcg/mL
geometric mean (confidence interval 95%)
Common serotypes - serotype 4	4.16 (1.16 to 14.91)	4.92 (1.94 to 12.5)
Common serotypes - serotype 6B	16.49 (4.31 to 63.06)	22.94 (10.84 to 48.52)
Common serotypes - serotype 9V	3.22 (1.2 to 8.64)	5.16 (2.34 to 11.37)
Common serotypes - serotype 14	9.02 (2.18 to 37.29)	16.99 (6.08 to 47.48)
Common serotype - serotype 18C	4.22 (2.22 to 8.05)	5.08 (2.43 to 10.63)
Common serotype - serotype 19F	3.39 (0.78 to 14.78)	6.45 (4.23 to 9.83)
Common serotype - serotype 23F	4.94 (1.82 to 13.41)	5.41 (2.3 to 12.74)
Additional serotype - serotype 1	9.37 (2.89 to 30.34)	1.25 (0.64 to 2.46)
Additional serotype - serotype 3	1.65 (1.13 to 2.4)	1.91 (1.06 to 3.46)
Additional serotype - serotype 5	4.51 (2.77 to 7.34)	2.31 (1.41 to 3.78)
Additional serotype - serotype 6A	7.42 (1.77 to 31.06)	4.46 (2.09 to 9.48)
Additional serotype - serotype 7F	8.81 (3.32 to 23.39)	3.14 (1.93 to 5.08)
Additional serotype - serotype 19A	4.4 (2.96 to 6.54)	5.61 (2.69 to 11.7)

Notes
[60] - N=number of subjects with a determinate antibody concentration to the specified serotype.
[61] - N=number of subjects with a determinate antibody concentration to the specified serotype.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving Opsonophagocytic Assay (OPA) Titers ≥Lower Limit of Quantitation (LLOQ) Measured 1 Month After the Infant Series

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End point title

Percentage of Subjects Achieving Opsonophagocytic Assay (OPA) Titers ≥Lower Limit of Quantitation (LLOQ) Measured 1 Month After the Infant Series ^[62]

End point description

Percentage of subjects in 13vPnC Groups 1, 2, and 3 achieving OPA with 95% CI for serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. Exact 2-sided CI based upon the observed proportion of subjects. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Limit of detection (LOD) established as lowest titer possible in assay, which was 8. OPA titers below LLOQ set to 0.5*LOD for analysis. Evaluable immunogenicity population.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3

Notes
[62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11 ^[63]	5 ^[64]	3 ^[65]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	88.9 (51.8 to 99.7)	75 (19.4 to 99.4)	66.7 (9.4 to 99.2)
Common serotypes - serotype 6B	100 (66.4 to 100)	100 (39.8 to 100)	100 (15.8 to 100)
Common serotypes - serotype 9V	30 (6.7 to 65.2)	0 (0 to 70.8)	66.7 (9.4 to 99.2)
Common serotypes - serotype 14	100 (54.1 to 100)	75 (19.4 to 99.4)	100 (15.8 to 100)
Common serotype - serotype 18C	100 (59 to 100)	100 (39.8 to 100)	100 (15.8 to 100)
Common serotype - serotype 19F	88.9 (51.8 to 99.7)	50 (6.8 to 93.2)	0 (0 to 97.5)
Common serotype - serotype 23F	88.9 (51.8 to 99.7)	66.7 (9.4 to 99.2)	100 (15.8 to 100)
Additional serotype - serotype 1	60 (26.2 to 87.8)	0 (0 to 60.2)	33.3 (0.8 to 90.6)
Additional serotype - serotype 3	90.9 (58.7 to 99.8)	100 (47.8 to 100)	100 (29.2 to 100)
Additional serotype - serotype 5	70 (34.8 to 93.3)	60 (14.7 to 94.7)	33.3 (0.8 to 90.6)
Additional serotype - serotype 6A	90 (55.5 to 99.7)	100 (47.8 to 100)	100 (29.2 to 100)
Additional serotype - serotype 7F	100 (69.2 to 100)	100 (47.8 to 100)	100 (15.8 to 100)
Additional serotype - serotype 19A	80 (44.4 to 97.5)	75 (19.4 to 99.4)	100 (15.8 to 100)

Notes
[63] - N=number of subjects with a determinate antibody concentration to the specified serotype.
[64] - N=number of subjects with a determinate antibody concentration to the specified serotype.
[65] - N=number of subjects with a determinate antibody concentration to the specified serotype.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Toddler Dose

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End point title

Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Toddler Dose ^[66]

End point description

Percentage of subjects in 13vPnC Groups 1, 2 and 3 achieving OPA with 95% CI for serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. Exact 2-sided CI based upon the observed proportion of subjects. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Limit of detection (LOD) established as lowest titer possible in assay, which was 8. OPA titers below LLOQ set to 0.5*LOD for analysis. Evaluable immunogenicity population.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2 ^[67]	6 ^[68]	1 ^[69]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (15.8 to 100)	50 (11.8 to 88.2)	100 (2.5 to 100)
Common serotypes - serotype 6B	100 (15.8 to 100)	80 (28.4 to 99.5)	100 (2.5 to 100)
Common serotypes - serotype 9V	100 (15.8 to 100)	83.3 (35.9 to 99.6)	100 (2.5 to 100)
Common serotypes - serotype 14	100 (15.8 to 100)	100 (29.2 to 100)	100 (2.5 to 100)
Common serotype - serotype 18C	100 (2.5 to 100)	80 (28.4 to 99.5)	100 (2.5 to 100)
Common serotype - serotype 19F	100 (15.8 to 100)	60 (14.7 to 94.7)	100 (2.5 to 100)
Common serotype - serotype 23F	100 (15.8 to 100)	100 (47.8 to 100)	100 (2.5 to 100)
Additional serotype - serotype 1	100 (15.8 to 100)	83.3 (35.9 to 99.6)	100 (2.5 to 100)
Additional serotype - serotype 3	100 (15.8 to 100)	100 (54.1 to 100)	100 (2.5 to 100)
Additional serotype - serotype 5	100 (15.8 to 100)	66.7 (22.3 to 95.7)	100 (2.5 to 100)
Additional serotype - serotype 6A	100 (15.8 to 100)	100 (54.1 to 100)	100 (2.5 to 100)
Additional serotype - serotype 7F	100 (15.8 to 100)	100 (54.1 to 100)	100 (2.5 to 100)
Additional serotype - serotype 19A	100 (15.8 to 100)	100 (47.8 to 100)	100 (2.5 to 100)

Notes
[67] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[68] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[69] - N=number of subjects with a determinate OPA antibody titer to the given serotype.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Relevant Catch-up Dose

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End point title

Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Relevant Catch-up Dose ^[70]

End point description

Percentage of subjects in 13vPnC Groups 4 and 5 achieving OPA with 95% CI for serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. Exact 2-sided CI based upon the observed proportion of subjects. The LLOQ in titers for each serotype was: Pn001, 18; Pn003, 12; Pn004, 21; Pn005, 29; Pn06A, 37; Pn06B, 43, Pn7F, 210; Pn09V, 345; Pn014, 35; Pn18C, 31; Pn19A, 18; Pn19F, 48; and Pn23F, 13. Limit of detection (LOD) established as lowest titer possible in assay, which was 8. OPA titers below LLOQ set to 0.5*LOD for analysis. Evaluable immunogenicity population.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[71]	8 ^[72]
Units: Percentage of Subjects
number (confidence interval 95%)
Common serotypes - serotype 4	100 (29.2 to 100)	100 (63.1 to 100)
Common serotypes - serotype 6B	100 (29.2 to 100)	100 (54.1 to 100)
Common serotypes - serotype 9V	100 (39.8 to 100)	100 (54.1 to 100)
Common serotypes - serotype 14	100 (15.8 to 100)	100 (54.1 to 100)
Common serotype - serotype 18C	100 (29.2 to 100)	100 (54.1 to 100)
Common serotype - serotype 19F	100 (29.2 to 100)	100 (54.1 to 100)
Common serotype - serotype 23F	100 (29.2 to 100)	100 (54.1 to 100)
Additional serotype - serotype 1	100 (39.8 to 100)	87.5 (47.3 to 99.7)
Additional serotype - serotype 3	100 (39.8 to 100)	100 (63.1 to 100)
Additional serotype - serotype 5	100 (39.8 to 100)	75 (34.9 to 96.8)
Additional serotype - serotype 6A	100 (39.8 to 100)	87.5 (47.3 to 99.7)
Additional serotype - serotype 7F	100 (39.8 to 100)	100 (63.1 to 100)
Additional serotype - serotype 19A	100 (39.8 to 100)	100 (47.8 to 100)

Notes
[71] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[72] - N=number of subjects with a determinate OPA antibody titer to the given serotype.

No statistical analyses for this end point

Other pre-specified: Pneumococcal OPA Geometric Mean Titers (GMTs) 1 Month After the Infant Series

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End point title

Pneumococcal OPA Geometric Mean Titers (GMTs) 1 Month After the Infant Series ^[73]

End point description

Antibody geometric mean titers as measured by OPA assay 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). GMTs were calculated using all subjects with available data for the specified blood draw. CIs for the GMTs are back transformations of confidence levels based on the Student t distribution for the mean logarithm of the titers. Evaluable immunogenicity population. Here "-99999" and "99999"in the 95% CI signifies NA. For reporting group 13vPnC Group 2 and in common serotype 19F of reporting group 13vPnC Group 3, NA signifies that within group, confidence intervals for serotypes for which subjects all have the same titer value were not computed since variability cannot be estimated. For reporting group 13vPnC Group 3, NA =1.3309*10^8.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11 ^[74]	5 ^[75]	3 ^[76]
Units: Titers
geometric mean (confidence interval 95%)
Common serotypes - serotype 4	123 (38.4 to 390.6)	116 (3.1 to 4294.7)	36 (0.3 to 4185.7)
Common serotypes - serotype 9V	20 (3.1 to 123.1)	4 (-99999 to 99999)	120 (0.1 to 199619.2)
Common serotype - serotype 19F	151 (49.6 to 457.7)	31 (0.7 to 1348.9)	4 (-99999 to 99999)
Common serotype - serotype 23F	299 (79.5 to 1124.8)	81 (0.1 to 52488.1)	566 (182.6 to 1755.9)
Additional serotype - serotype 1	41 (9.2 to 183.5)	4 (-99999 to 99999)	7 (0.5 to 109.4)
Additional serotype - serotype 3	58 (28.9 to 117.7)	82 (21.7 to 311.6)	206 (66.1 to 639)
Additional serotype - serotype 5	26 (9.6 to 72.3)	18 (2.9 to 110.8)	9 (0.3 to 234.5)
Additional serotype - serotype 6A	731 (182.2 to 2933.6)	1069 (337.1 to 3390.4)	984 (179.7 to 5383.5)
Additional serotype - serotype 7F	1396 (790.5 to 2467)	1177 (692.5 to 2001.6)	3485 (2308.5 to 5261.5)
Common serotype - serotype 6B	1280 (610.3 to 2683.5)	1450 (370.4 to 5675.6)	1790 (0 to 72147076)
Common serotype - serotype 14	332 (98 to 1124.2)	71 (3.3 to 1516)	449 (0.1 to 2059598)
Common serotype - serotype 18C	868 (304.4 to 2475)	452 (67.7 to 3023.6)	906 (0.6 to 1340206)
Additional serotype - serotype 19A	58 (17.7 to 191.3)	158 (2.5 to 9872.6)	380 (0 to 99999)

Notes
[74] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[75] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[76] - N=number of subjects with a determinate OPA antibody titer to the given serotype.

No statistical analyses for this end point

Other pre-specified: Pneumococcal OPA GMTs 1 Month After the Toddler Dose

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End point title

Pneumococcal OPA GMTs 1 Month After the Toddler Dose ^[77]

End point description

Antibody geometric mean titers as measured by OPA assay 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). GMTs were calculated using all subjects with available data for the specified blood draw. CIs for the GMTs are back transformations of confidence levels based on the Student t distribution for the mean logarithm of the titers. Evaluable immunogenicity population. Here "-99999" and "-99999" in 95% CI signifies NA. For reporting group 13vPnC Group 3 and in common serotype 18C of reporting group 13vPnC Group 1, NA signifies that within group, confidence intervals for serotypes with only 1 subject who had a determinate OPA antibody titer were not computed since variability cannot be estimated. For reporting group 13vPnC Group 1, in common serotype 6B, 19F, 23F and additional serotype 6A NA =2.4794*10^8, 2.4862*10^8, 1.208*10^12 and 1.9613*10^9 respectively.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, after vaccination 2 for Group 3

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2 ^[78]	6 ^[79]	1 ^[80]
Units: Titers
geometric mean (confidence interval 95%)
Common serotypes - serotype 4	599 (422.4 to 850.2)	58 (2.6 to 1317.2)	220 (-99999 to 99999)
Common serotypes - serotype 9V	428 (68.2 to 2681.9)	460 (35 to 6035.8)	2765 (-99999 to 99999)
Common serotypes - serotype 14	775 (5.8 to 104290.7)	551 (73.6 to 4120.2)	779 (-99999 to 99999)
Common serotype - serotype 18C	3311 (-99999 to 99999)	387 (14.8 to 10145.6)	4316 (-99999 to 99999)
Additional serotype - serotype 1	46 (0.1 to 14754.5)	66 (14.4 to 305.2)	165 (-99999 to 99999)
Additional serotype - serotype 3	159 (0.2 to 141793.2)	138 (60.9 to 313.7)	402 (-99999 to 99999)
Additional serotype - serotype 5	87 (0.8 to 9175.7)	30 (5.4 to 164.2)	88 (-99999 to 99999)
Additional serotype - serotype 7F	4590 (258.5 to 81484.1)	1575 (810.3 to 3061.7)	6105 (-99999 to 99999)
Additional serotype - serotype 19A	1259 (210.3 to 7542.2)	140 (22.7 to 860.3)	427 (-99999 to 99999)
Common serotype - serotype 6B	1565 (0 to 99999)	605 (17.1 to 21473.7)	12470 (-99999 to 99999)
Common serotype - serotype 19F	397 (0 to 99999)	73 (2.5 to 2087.3)	532 (-99999 to 99999)
Common serotype - serotype 23F	227 (0 to 99999)	313 (30.6 to 3195.2)	1660 (-99999 to 99999)
Additional serotype - serotype 6A	3207 (0 to 99999)	1688 (480.3 to 5929.3)	6954 (-99999 to 99999)

Notes
[78] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[79] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[80] - N=number of subjects with a determinate OPA antibody titer to the given serotype.

No statistical analyses for this end point

Other pre-specified: Pneumococcal OPA GMTs 1 Month After the Relevant Catch-up Dose

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End point title

Pneumococcal OPA GMTs 1 Month After the Relevant Catch-up Dose ^[81]

End point description

Antibody geometric mean titers as measured by OPA assay for 13 pneumococcal serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). GMTs were calculated using all subjects with available data for the specified blood draw. CIs for the GMTs are back transformations of confidence levels based on the Student t distribution for the mean logarithm of the titers. Evaluable immunogenicity population.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4 ^[82]	8 ^[83]
Units: Titers
geometric mean (confidence interval 95%)
Common serotypes - serotype 4	594 (107.1 to 3295.5)	1165 (261.1 to 5197.9)
Common serotypes - serotype 6B	7236 (3423.7 to 15294)	6795 (795.9 to 58012.5)
Common serotypes - serotype 9V	2748 (457.9 to 16485.4)	2979 (883.6 to 10040.5)
Common serotypes - serotype 14	1159 (31.2 to 42979.5)	1547 (347.4 to 6892.2)
Common serotype - serotype 18C	5910 (1824.6 to 19141.1)	1871 (915.7 to 3824.2)
Common serotype - serotype 19F	1584 (463.4 to 5417.3)	594 (84.8 to 4164.9)
Common serotype - serotype 23F	2870 (2572.2 to 3203.4)	1240 (423 to 3632.5)
Additional serotype - serotype 1	402 (285.8 to 564.7)	62 (18 to 211.6)
Additional serotype - serotype 3	218 (102 to 466.8)	202 (136 to 299.3)
Additional serotype - serotype 5	128 (15.9 to 1032)	63 (13.3 to 302.2)
Additional serotype - serotype 6A	9067 (5187 to 15848.5)	2292 (231.2 to 22724)
Additional serotype - serotype 7F	7776 (3701.3 to 16335.8)	6086 (2680.9 to 13818.2)
Additional serotype - serotype 19A	815 (549.9 to 1206.8)	400 (68.4 to 2344.7)

Notes
[82] - N=number of subjects with a determinate OPA antibody titer to the given serotype.
[83] - N=number of subjects with a determinate OPA antibody titer to the given serotype.

No statistical analyses for this end point

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Infant Series

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End point title

Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Infant Series ^[84]

End point description

Correlative analysis output data are only available as figures and were not analyzed or presented statistically. Here "99999" in number signifies NA. Correlative analysis output data are only available as figures and were not analyzed or presented statistically.

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 3 for Group 1, after vaccination 2 for Group 2, and after vaccination 1 for Group 3

Notes
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	11	5	3
Units: Subjects
number (not applicable)	99999	99999	99999

No statistical analyses for this end point

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Toddler Dose

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End point title

Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Toddler Dose ^[85]

End point description

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 4 for Group 1, after vaccination 3 for Group 2, and after vaccination 2 for Group 3

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received infant dose and toddler dose.

End point values	13vPnC Group 1 (3 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 2 (2 Doses Infant Series and 1 Toddler Dose)	13vPnC Group 3 (1 Dose Infant Series and 1 Toddler Dose)
Number of subjects analysed	2	6	1
Units: Subjects
number (not applicable)	99999	99999	99999

No statistical analyses for this end point

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Relevant Catch-up Dose

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End point title

Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Relevant Catch-up Dose ^[86]

End point description

End point type

Other pre-specified

End point timeframe

28 to 56 days after vaccination 2 for Group 4, and after the single vaccination in Group 5

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint was planned to be assessed for subjects who received catch-up dose.

End point values	13vPnC Group 4 (2 Catch-Up Doses)	13vPnC Group 5 (1 Catch-Up Dose)
Number of subjects analysed	4	8
Units: Subjects
number (not applicable)	99999	99999

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Randomization to 6 months after last vaccination

Adverse event reporting additional description

Same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as non serious in another subject, or one subject may have experienced both events. Version was not captured, here 0.0 is mentioned for dictionary version.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

0.0

Reporting group title

Group 1 (Infant Series)

Reporting group description

Subjects 6 weeks <10 months of age with 0 prior doses of Prevnar received 3 single IM 0.5 mL doses of 13vPnC at least 28 days apart (infant series).

Reporting group title

Group 2 (Infant Series)

Reporting group description

Subjects <12 months of age with 1 prior dose of Prevnar received 2 single IM 0.5 mL doses of 13vPnC at least 28 days apart (infant series).

Reporting group title

Group 3 (Infant Series)

Reporting group description

Subjects <12 months of age with 2 prior doses of Prevnar received a single IM 0.5 mL dose of 13vPnC (infant series).

Reporting group title

Group 1 (Toddler Dose)

Reporting group description

Subjects >12 months of age received a single IM 0.5 mL dose of 13vPnC at least 60 days after last infant dose (toddler dose).

Reporting group title

Group 2 (Toddler Dose)

Reporting group description

Subjects >12 months of age received a single IM 0.5 mL dose of 13vPnC at least 60 days after last infant dose (toddler dose).

Reporting group title

Group 3 (Toddler Dose)

Reporting group description

Subjects >12 months of age received a single IM 0.5 mL dose of 13vPnC at least 60 days after last infant dose (toddler dose)

Reporting group title

Group 4 (2 Catch-Up Doses)

Reporting group description

Subjects >=12 months to <2 years of age received 2 single IM 0.5 mL doses of 13vPnC at least 60 days apart.

Reporting group title

Group 5 (1 Catch-Up Dose)

Reporting group description

Subjects >=2 years to <5 years of age received a single IM 0.5 mL dose of 13vPnC.

Reporting group title

Group 1 (Infant Series) Follow-up

Reporting group description

Subjects 6 weeks to <10 months of age with 0 prior doses of Prevnar received 3 single IM 0.5 mL doses of 13vPnC at least 28 days apart were assessed from last 13vPnC Dose blood draw to the 6-month follow-up telephone contact.

Reporting group title

Group 2 (Infant Series) Follow-up

Reporting group description

Subjects <12 months of age with 1 prior dose of Prevnar received 2 single IM 0.5 mL doses of 13vPnC at least 28 days apart were assessed from last 13vPnC Dose blood draw to the 6-month follow-up telephone contact.

Reporting group title

Group 3 (Infant Series) Follow-up

Reporting group description

Subjects <12 months of age with 2 prior doses of Prevnar received a single IM 0.5 mL dose of 13vPnC were assessed from last 13vPnC Dose blood draw to the 6-month follow-up telephone contact.

Reporting group title

Group 4 (2 Catch-Up Doses) Follow-up

Reporting group description

Subjects >=12 months to <2 years of age received 2 single IM 0.5 mL doses of 13vPnC at least 60 days apart were assessed from last 13vPnC Dose blood draw to the 6-month follow-up telephone contact.

Reporting group title

Group 5 (1 Catch-Up Dose) Follow-up

Reporting group description

Subjects >=2 years to <5 years of age received a single IM 0.5 mL dose of 13vPnC were assessed from last 13vPnC Dose blood draw to the 6-month follow-up telephone contact.

Reporting group title

Group 1 (After Infant Series)

Reporting group description

Subjects 6 weeks <10 months of age with 0 prior doses of Prevnar received 3 single IM 0.5 mL doses of 13vPnC at least 28 days apart in infant series.

Reporting group title

Group 2 (After Infant Series)

Reporting group description

Subjects <12 months of age with 1 prior dose of Prevnar received 2 single IM 0.5 mL doses of 13vPnC at least 28 days apart in infant series.

Reporting group title

Group 3 (After Infant Series)

Reporting group description

Subjects <12 months of age with 2 prior doses of Prevnar received a single IM 0.5 mL dose of 13vPnC in infant series.

Group 1 (Infant Series)

Group 2 (Infant Series)

Group 3 (Infant Series)

Group 1 (Toddler Dose)

Group 2 (Toddler Dose)

Group 3 (Toddler Dose)

Group 4 (2 Catch-Up Doses)

Group 5 (1 Catch-Up Dose)

Group 1 (Infant Series) Follow-up

Group 2 (Infant Series) Follow-up

Group 3 (Infant Series) Follow-up

Group 4 (2 Catch-Up Doses) Follow-up

Group 5 (1 Catch-Up Dose) Follow-up

Group 1 (After Infant Series)

Group 2 (After Infant Series)

Group 3 (After Infant Series)

Total subjects affected by serious adverse events

subjects affected / exposed

21 / 151 (13.91%)

2 / 51 (3.92%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

2 / 16 (12.50%)

3 / 66 (4.55%)

0 / 79 (0.00%)

6 / 151 (3.97%)

6 / 51 (11.76%)

1 / 25 (4.00%)

1 / 66 (1.52%)

1 / 79 (1.27%)

4 / 151 (2.65%)

2 / 51 (3.92%)

4 / 25 (16.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Foreign body

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

1 / 151 (0.66%)

1 / 51 (1.96%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Laryngomalacia

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Convulsion

subjects affected / exposed

3 / 151 (1.99%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 3

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Febrile convulsion

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

1 / 51 (1.96%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lymphadenitis

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Pyrexia

subjects affected / exposed

2 / 151 (1.32%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Sudden infant death syndrome

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Gastrointestinal disorders

Gastrooesophageal reflux disease

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration

subjects affected / exposed

2 / 151 (1.32%)

1 / 51 (1.96%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 2

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Asthma

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchial hyperreactivity

subjects affected / exposed

0 / 151 (0.00%)

1 / 51 (1.96%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Respiratory distress

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Apnoea

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Eczema

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Breath holding

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Pneumonia

subjects affected / exposed

4 / 151 (2.65%)

0 / 51 (0.00%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

2 / 151 (1.32%)

3 / 51 (5.88%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

2 / 151 (1.32%)

1 / 51 (1.96%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 3

0 / 0

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 1

0 / 0

Respiratory syncytial virus bronchiolitis

subjects affected / exposed

5 / 151 (3.31%)

1 / 51 (1.96%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

2 / 151 (1.32%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 5

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

3 / 151 (1.99%)

1 / 51 (1.96%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 3

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia respiratory syncytial viral

subjects affected / exposed

3 / 151 (1.99%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

1 / 51 (1.96%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchiolitis

subjects affected / exposed

2 / 151 (1.32%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

2 / 151 (1.32%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis staphylococcal

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis haemophilus

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Septic arthritis haemophilus

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper respiratory tract infection

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis viral

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abscess

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpangina

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Croup infectious

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

1 / 51 (1.96%)

1 / 25 (4.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arthritis bacterial

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Streptococcal bacteraemia

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

1 / 79 (1.27%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Eczema infected

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Genital abscess

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

1 / 51 (1.96%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin infection

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Tracheobronchitis

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Hyponatraemia

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dehydration

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

1 / 25 (4.00%)

0 / 66 (0.00%)

1 / 79 (1.27%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Group 1 (Infant Series)

Group 2 (Infant Series)

Group 3 (Infant Series)

Group 1 (Toddler Dose)

Group 2 (Toddler Dose)

Group 3 (Toddler Dose)

Group 4 (2 Catch-Up Doses)

Group 5 (1 Catch-Up Dose)

Group 1 (Infant Series) Follow-up

Group 2 (Infant Series) Follow-up

Group 3 (Infant Series) Follow-up

Group 4 (2 Catch-Up Doses) Follow-up

Group 5 (1 Catch-Up Dose) Follow-up

Group 1 (After Infant Series)

Group 2 (After Infant Series)

Group 3 (After Infant Series)

Total subjects affected by non serious adverse events

subjects affected / exposed

11 / 151 (7.28%)

4 / 51 (7.84%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

Nervous system disorders

Convulsion

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences all number

Crying

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences all number

General disorders and administration site conditions

Pyrexia

subjects affected / exposed

9 / 151 (5.96%)

4 / 51 (7.84%)

1 / 25 (4.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences all number

Injection site erythema

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences all number

Injection site swelling

subjects affected / exposed

1 / 151 (0.66%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences all number

Skin and subcutaneous tissue disorders

Rash maculo-papular

subjects affected / exposed

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 15 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 66 (1.52%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

0 / 66 (0.00%)

0 / 79 (0.00%)

0 / 151 (0.00%)

0 / 51 (0.00%)

0 / 25 (0.00%)

occurrences all number

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

29 Aug 2008

Follow up for safety assessment for 6 months after last vaccination was added; a local data safety monitoring board (DSMB) in accordance with the local Alaska Area IRB requirements was added and details on the ongoing safety review by the DSMB were to be provided in a separate charter.

15 Oct 2008

Timing of nasopharyngeal (NP) colonization swab collection was corrected to reflect annual timing. Study flow charts were updated for clarity regarding vaccine dosing intervals.

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, Open Label Trial Evaluating the Safety, Immunogenicity and Impact of 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series

Primary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody Level ≥0.35 Micrograms Per Milliliter (Mcg/mL) 1 Month After the Infant Series

Primary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Toddler Dose

Primary: Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Toddler Dose

Primary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Relevant Catch-Up Dose

Primary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.35 Mcg/mL 1 Month After the Relevant Catch-Up Dose

Primary: Number of Cases of Invasive Pneumococcal Disease (IPD) in Subjects Less Than 5 Years of Age Due to Any Serotype Contained in 13vPnC

Primary: Number of Cases of Invasive Pneumococcal Disease (IPD) in Subjects Less Than 5 Years of Age Due to Any Serotype Contained in 13vPnC

Secondary: Percentage of Subjects Achieving Serum IgG Antibody Level ≥0.35 Mcg/mL Prior to Vaccination With 13vPnC (Groups 4 and 5 Only)

Secondary: Percentage of Subjects Achieving Serum IgG Antibody Level ≥0.35 Mcg/mL Prior to Vaccination With 13vPnC (Groups 4 and 5 Only)

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Infant Series

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Toddler Dose

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Relevant Catch-up Dose

Secondary: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥1.0 Mcg/mL 1 Month After the Relevant Catch-up Dose

Secondary: Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 1

Secondary: Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 1

Secondary: Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 2

Secondary: Percentage of Subjects Reporting Pre-Specified Local Reactions: Catch-up Dose 2

Secondary: Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 1

Secondary: Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 1

Secondary: Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 2

Secondary: Percentage of Subjects Reporting Pre-Specified Systemic Events: Catch-up Dose 2

Other pre-specified: Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Infant Series

Other pre-specified: Percentage of Subjects Achieving Serotype-Specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Infant Series

Other pre-specified: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Relevant Catch-up Dose

Other pre-specified: Percentage of Subjects Achieving Serotype-specific Pneumococcal IgG Antibody Level ≥0.15 Mcg/mL 1 Month After the Relevant Catch-up Dose

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Infant Series

Other pre-specified: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Infant Series

Other pre-specified: GMC for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Toddler Dose

Other pre-specified: GMC for Serotype-Specific Pneumococcal IgG Antibodies 1 Month After the Toddler Dose

Other pre-specified: GMC for Serotype-specific Pneumococcal IgG Antibodies 1 Month After the Relevant Catch-up Dose

Other pre-specified: GMC for Serotype-specific Pneumococcal IgG Antibodies 1 Month After the Relevant Catch-up Dose

Other pre-specified: Percentage of Subjects Achieving Opsonophagocytic Assay (OPA) Titers ≥Lower Limit of Quantitation (LLOQ) Measured 1 Month After the Infant Series

Other pre-specified: Percentage of Subjects Achieving Opsonophagocytic Assay (OPA) Titers ≥Lower Limit of Quantitation (LLOQ) Measured 1 Month After the Infant Series

Other pre-specified: Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Toddler Dose

Other pre-specified: Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Relevant Catch-up Dose

Other pre-specified: Percentage of Subjects Achieving OPA Titers ≥LLOQ Measured 1 Month After the Relevant Catch-up Dose

Other pre-specified: Pneumococcal OPA Geometric Mean Titers (GMTs) 1 Month After the Infant Series

Other pre-specified: Pneumococcal OPA Geometric Mean Titers (GMTs) 1 Month After the Infant Series

Other pre-specified: Pneumococcal OPA GMTs 1 Month After the Toddler Dose

Other pre-specified: Pneumococcal OPA GMTs 1 Month After the Toddler Dose

Other pre-specified: Pneumococcal OPA GMTs 1 Month After the Relevant Catch-up Dose

Other pre-specified: Pneumococcal OPA GMTs 1 Month After the Relevant Catch-up Dose

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Infant Series

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Infant Series

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Toddler Dose

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Toddler Dose

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Relevant Catch-up Dose

Other pre-specified: Correlation of OPA and IgG Values for Each 13vPnC Serotype 1 Month After the Relevant Catch-up Dose

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 3, Open Label Trial Evaluating the Safety, Immunogenicity and Impact of 13-valent Pneumococcal Conjugate Vaccine (13vPnC) in Alaskan Native Children.