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Clinical Trial Results:
A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine in Children With Sickle Cell Disease Previously Immunized With 23-valent Pneumococcal Polysaccharide Vaccine

Summary
EudraCT number	2009-011396-77
Trial protocol	FR GB IT Outside EU/EEA
Global end of trial date	28 Mar 2013

Results information
Results version number	v1(current)
This version publication date	29 Jun 2016
First version publication date	01 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

B1851013 (6096A1-3014)

ISRCTN number

US NCT number

NCT00918580

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., +1 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., +1 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

04 Jun 2013

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Mar 2013

Was the trial ended prematurely?

Main objective of the trial

To evaluate the immune response 1 month after 2 doses of 13-valent pneumococcal conjugate vaccine (13vPnC) given 6 months apart compared to 1 month after 1 dose of 13vPnC as measured by fold rise in serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in children with sickle cell disease (SCD) who had been previously vaccinated with at least 1 dose of 23-valent pneumococcal polysaccharide vaccine (23vPS).

Protection of trial subjects

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

Background therapy

Evidence for comparator

Actual start date of recruitment

03 Nov 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Efficacy, Safety

Long term follow-up duration

12 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 27

Country: Number of subjects enrolled

France: 9

Country: Number of subjects enrolled

Italy: 11

Country: Number of subjects enrolled

Saudi Arabia: 3

Country: Number of subjects enrolled

Lebanon: 56

Country: Number of subjects enrolled

Egypt: 23

Country: Number of subjects enrolled

United States: 29

Worldwide total number of subjects

158

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)

Children (2-11 years)

Adolescents (12-17 years)

105

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

This study was conducted in the United States of America (USA), United Kingdom, Italy, Lebanon, Egypt, France, and Saudi Arabia. Children with sickle cell disease, of 6 years to less than 18 years of age, previously immunized with 23vPS at least 6 months ago, were enrolled in this study.

Period 1 title

Up to 6-month Follow-up (FU)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

13vPnC

Arm description

Subjects previously immunized with 23vPS received 2 single 0.5 milliliter (mL) doses of 13vPnC intramuscular injection, 6 months apart.

Arm type

Experimental

Investigational medicinal product name

13-valent pneumococcal conjugate vaccine

Investigational medicinal product code

13vPnC

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 single 0.5 mL doses of 13vPnC intramuscular injection, 6 months apart.

Number of subjects in period 1	13vPnC
Started	158
Vaccinated Dose 1	158
Vaccinated Dose 2	146 ^[1]
Completed	147
Not completed	11
Consent withdrawn by subject	2
'Parent/Legal Guardian Request '	2
Adverse event, non-fatal	1
'Failed to Return '	1
Lost to follow-up	5

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: This milestone included 1 subject who withdrew before Dose 2 (protocol violation) but completed 6-month follow-up period.

Period 2 title

After 6-month FU to 1-year FU

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

13vPnC

Arm description

Subjects previously immunized with 23vPS received 2 single 0.5 mL doses of 13vPnC intramuscular injection, 6 months apart in Period 1.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 2	13vPnC
Started	147
Continued After 6-Month FU	89
Completed	87
Not completed	60
'Did Not Continue After 6-Month FU '	58
'Failed to Return '	2

Baseline characteristics

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Reporting group title

13vPnC

Reporting group description

Subjects previously immunized with 23vPS received 2 single 0.5 milliliter (mL) doses of 13vPnC intramuscular injection, 6 months apart.

Reporting group values	13vPnC	Total
Number of subjects	158	158
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	13.3 ( 3.08 )	-
Gender categorical
Units: Subjects
Female	76	76
Male	82	82

End points

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Reporting group title

13vPnC

Reporting group description

Subjects previously immunized with 23vPS received 2 single 0.5 milliliter (mL) doses of 13vPnC intramuscular injection, 6 months apart.

Reporting group title

13vPnC

Reporting group description

Subjects previously immunized with 23vPS received 2 single 0.5 mL doses of 13vPnC intramuscular injection, 6 months apart in Period 1.

Primary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 1 Month After 13vPnC Dose 1 to 1 Month After 13vPnC Dose 2

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End point title

Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 1 Month After 13vPnC Dose 1 to 1 Month After 13vPnC Dose 2 ^[1]

End point description

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from 1 month after 13vPnC Dose 1 to 1 month after 13vPnC Dose 2 were computed using logarithmically transformed assay results. Confidence interval (CI) for GMFR were back transformations of a CI based on Student t distribution for mean logarithm of the mean fold rise. GMFRs were calculated using all subjects with available data from both 1 month after 13vPnC Dose 1 and after 13vPnC Dose 2 blood draws. Analysis was done on the evaluable immunogenicity population- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. Here "N" signifies subjects with determinate IgG antibody concentration for the given serotype at both the time points 1 Month After 13vPnC Dose 1 and 1 Month After 13vPnC Dose 2 blood draws. Subjects may be represented in more than 1 category.

End point type

Primary

End point timeframe

1 Month After 13vPnC Dose 1, 1 Month After 13vPnC Dose 2

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.

End point values	13vPnC
Number of subjects analysed	138 ^[2]
Units: fold rise
geometric mean (confidence interval 95%)
Serotype 4 (N = 137)	0.75 (0.66 to 0.84)
Serotype 6B (N = 136)	0.89 (0.78 to 1.02)
Serotype 9V (N = 136)	0.82 (0.75 to 0.91)
Serotype 14 (N = 137)	0.75 (0.67 to 0.85)
Serotype 18C (N = 137)	0.7 (0.62 to 0.8)
Serotype 19F (N = 136)	1.05 (0.91 to 1.2)
Serotype 23F (N = 135)	0.91 (0.77 to 1.08)
Serotype 1 (N = 137)	0.88 (0.77 to 0.99)
Serotype 3 (N = 134)	0.82 (0.75 to 0.9)
Serotype 5 (N = 136)	0.9 (0.82 to 0.98)
Serotype 6A (N = 136)	0.95 (0.82 to 1.1)
Serotype 7F (N = 137)	0.75 (0.67 to 0.85)
Serotype 19A (N = 137)	0.83 (0.74 to 0.93)

Notes
[2] - Number of subjects analyzed signifies the evaluable immunogenicity population.

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1

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End point title

Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1

End point description

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 1 to 1 month after 13vPnC Dose 1 were computed using logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on Student t distribution for mean logarithm of the mean fold rise. GMFRs were calculated using all subjects with available data from before 13vPnC Dose 1 and 1 month after 13vPnC Dose 1 blood draws. Analysis was done on the evaluable immunogenicity population- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. “N” signifies subjects with a determinate IgG antibody concentration for given serotype from before 13vPnC Dose 1 and 1 month after 13vPnC Dose 1 blood draws. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1

End point values	13vPnC
Number of subjects analysed	138 ^[3]
Units: Fold rise
geometric mean (confidence interval 95%)
Serotype 4 (N = 136)	6.91 (5.27 to 9.06)
Serotype 6B (N = 137)	4.72 (3.8 to 5.85)
Serotype 9V (N = 138)	3.1 (2.6 to 3.7)
Serotype 14 (N = 138)	5.5 (4.05 to 7.46)
Serotype 18C (N = 137)	5.58 (4.47 to 6.97)
Serotype 19F (N = 134)	4.76 (3.77 to 6.03)
Serotype 23F (N = 137)	6.58 (5.12 to 8.46)
Serotype 1 (N = 129)	3.6 (2.9 to 4.46)
Serotype 3 (N = 133)	2.03 (1.78 to 2.31)
Serotype 5 (N = 138)	1.74 (1.56 to 1.94)
Serotype 6A (N = 132)	4.1 (3.32 to 5.05)
Serotype 7F (N = 137)	4.38 (3.62 to 5.3)
Serotype 19A (N = 138)	3.28 (2.73 to 3.96)

Notes
[3] - Number of subjects analyzed signifies the evaluable immunogenicity population.

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 2 to 1 Month After 13vPnC Dose 2

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End point title

Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 2 to 1 Month After 13vPnC Dose 2

End point description

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) from before 13vPnC Dose 2 to 1 month after 13vPnC Dose 2 were computed using logarithmically transformed assay results. CI for GMFR were back transformations of a CI based on Student t distribution for mean logarithm of the mean fold rise. GMFRs were calculated using all subjects with available data from before 13vPnC Dose 2 and 1 month after 13vPnC Dose 2 blood draws. Analysis was done on the evaluable immunogenicity population- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. “N” signifies subject with a determinate IgG antibody concentration for given serotype from before 13vPnC Dose 2 and 1 month after 13vPnC Dose 2 blood draws. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

Before 13vPnC Dose 2, 1 month after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	138 ^[4]
Units: Fold rise
geometric mean (confidence interval 95%)
Serotype 4 (N = 137)	1.86 (1.69 to 2.04)
Serotype 6B (N = 137)	1.8 (1.69 to 2.03)
Serotype 9V (N = 136)	1.48 (1.37 to 1.59)
Serotype 14 (N = 137)	1.24 (1.15 to 1.35)
Serotype 18C (N = 137)	1.47 (1.34 to 1.62)
Serotype 19F (N = 135)	2.08 (1.85 to 2.34)
Serotype 23F (N = 135)	2.04 (1.75 to 2.37)
Serotype 1 (N = 136)	1.73 (1.57 to 1.92)
Serotype 3 (N = 133)	1.36 (1.25 to 1.47)
Serotype 5 (N = 135)	1.3 (1.22 to 1.39)
Serotype 6A (N = 133)	1.8 (1.6 to 2.02)
Serotype 7F (N = 137)	1.75 (1.61 to 1.9)
Serotype 19A (N = 137)	1.48 (1.36 to 1.61)

Notes
[4] - Number of subjects analyzed signifies the evaluable immunogenicity population.

No statistical analyses for this end point

Secondary: Ratio of Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 13vPnC Dose 1 to 13vPnC Dose 2

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End point title

Ratio of Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 13vPnC Dose 1 to 13vPnC Dose 2

End point description

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were computed using the logarithmically transformed assay results for Dose 1 (after Dose 1/before Dose 1) and for Dose 2 (after Dose 2/before Dose 2). CI for the ratio of GMFR (Dose 2/Dose 1) were back transformations of a CI based on the Student t distribution for the mean logarithm of the measures (Dose 2 – Dose 1). Analysis was done on the evaluable immunogenicity population- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. “N” signifies subject with a determinate IgG antibody concentration for given serotype at before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2 and 1 month after 13vPnC Dose 2 blood draws. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2, 1 month after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	138 ^[5]
Units: Ratio of GMFR
geometric mean (confidence interval 95%)
Serotype 4 (N = 135)	0.26 (0.2 to 0.35)
Serotype 6B (N = 136)	0.38 (0.29 to 0.49)
Serotype 9V (N = 136)	0.49 (0.41 to 0.59)
Serotype 14 (N = 137)	0.22 (0.16 to 0.31)
Serotype 18C (N = 136)	0.26 (0.21 to 0.34)
Serotype 19F (N = 132)	0.44 (0.34 to 0.57)
Serotype 23F (N = 135)	0.32 (0.24 to 0.43)
Serotype 1 (N = 127)	0.47 (0.37 to 0.59)
Serotype 3 (N = 130)	0.66 (0.58 to 0.75)
Serotype 5 (N = 135)	0.75 (0.66 to 0.85)
Serotype 6A (N = 127)	0.45 (0.35 to 0.58)
Serotype 7F (N = 136)	0.39 (0.32 to 0.49)
Serotype 19A (N = 137)	0.45 (0.36 to 0.55)

Notes
[5] - Number of subjects analyzed signifies the evaluable immunogenicity population.

No statistical analyses for this end point

Secondary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody

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End point title

Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody

End point description

Antibody GMC for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) were presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all subjects with available data for the specified blood draw. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Analysis was done on the evaluable immunogenicity population- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. "N" signifies subject with determinate IgG antibody concentration for the given serotype at specified time point. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2, 1 month after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	138 ^[6]
Units: microgram per milliliter (mcg/mL)
geometric mean (confidence interval 95%)
Before 13vPnC Dose 1: Serotype 4 (N = 136)	1.01 (0.8 to 1.27)
Before 13vPnC Dose 1: Serotype 6B (N = 138)	5.79 (4.89 to 6.87)
Before 13vPnC Dose 1: Serotype 9V (N = 138)	3.01 (2.56 to 3.53)
Before 13vPnC Dose 1: Serotype 14 (N = 138)	6.3 (4.78 to 8.3)
Before 13vPnC Dose 1: Serotype 18C (N = 137)	1.4 (1.14 to 1.73)
Before 13vPnC Dose 1: Serotype 19F (N = 134)	4.46 (3.6 to 5.53)
Before 13vPnC Dose 1: Serotype 23F (N = 138)	2.8 (2.38 to 3.3)
Before 13vPnC Dose 1: Serotype 1 (N = 129)	1.57 (1.26 to 1.95)
Before 13vPnC Dose 1: Serotype 3 (N = 133)	1.02 (0.83 to 1.25)
Before 13vPnC Dose 1: Serotype 5 (N = 138)	4.14 (3.58 to 4.78)
Before 13vPnC Dose 1: Serotype 6A (N = 132)	4.62 (3.91 to 5.46)
Before 13vPnC Dose 1: Serotype 7F (N = 137)	2.16 (1.8 to 2.59)
Before 13vPnC Dose 1: Serotype 19A (N = 138)	8.16 (7.03 to 9.48)
1 Month After 13vPnC Dose 1: Serotype 4 (N = 138)	6.85 (5.55 to 8.44)
1 Month After 13vPnC Dose 1: Serotype 6B (N= 137)	27.25 (22.09 to 33.61)
1 Month After 13vPnC Dose 1: Serotype 9V (N= 138)	9.31 (7.83 to 11.07)
1 Month After 13vPnC Dose 1: Serotype 14 (N = 138)	34.63 (27.77 to 43.18)
1 Month After 13vPnC Dose 1: Serotype 18C (N= 138)	7.83 (6.42 to 9.54)
1 Month After 13vPnC Dose 1: Serotype 19F (N= 138)	20.4 (16.03 to 25.95)
1 Month After 13vPnC Dose 1: Serotype 23F (N= 137)	18.25 (14.52 to 22.95)
1 Month After 13vPnC Dose 1: Serotype 1 (N = 138)	5.24 (4.3 to 6.39)
1 Month After 13vPnC Dose 1: Serotype 3 (N = 138)	2.04 (1.76 to 2.38)
1 Month After 13vPnC Dose 1: Serotype 5 (N = 138)	7.19 (6.19 to 8.35)
1 Month After 13vPnC Dose 1: Serotype 6A (N = 138)	17.61 (14.16 to 21.91)
1 Month After 13vPnC Dose 1: Serotype 7F (N = 138)	9.46 (8.17 to 10.94)
1 Month After 13vPnC Dose 1: Serotype 19A (N= 138)	26.82 (22.16 to 32.46)
Before 13vPnC Dose 2: Serotype 4 (N = 138)	2.77 (2.29 to 3.35)
Before 13vPnC Dose 2: Serotype 6B (N = 138)	13.67 (11.23 to 16.63)
Before 13vPnC Dose 2: Serotype 9V (N = 138)	5.19 (4.41 to 6.09)
Before 13vPnC Dose 2: Serotype 14 (N = 138)	21.07 (17.29 to 25.67)
Before 13vPnC Dose 2: Serotype 18C (N = 138)	3.73 (3.1 to 4.49)
Before 13vPnC Dose 2: Serotype 19F (N = 137)	10.34 (8.32 to 12.85)
Before 13vPnC Dose 2: Serotype 23F (N = 137)	8.07 (6.63 to 9.83)
Before 13vPnC Dose 2: Serotype 1 (N = 137)	2.65 (2.21 to 3.19)
Before 13vPnC Dose 2: Serotype 3 (N = 135)	1.27 (1.06 to 1.52)
Before 13vPnC Dose 2: Serotype 5 (N = 137)	4.91 (4.26 to 5.66)
Before 13vPnC Dose 2: Serotype 6A (N = 135)	9.05 (7.48 to 10.95)
Before 13vPnC Dose 2: Serotype 7F (N = 138)	4.09 (3.52 to 4.74)
Before 13vPnC Dose 2: Serotype 19A (N = 138)	15.13 (12.73 to 17.98)
1 Month After 13vPnC Dose 2: Serotype 4 (N = 137)	5.09 (4.28 to 6.04)
1 Month After 13vPnC Dose 2: Serotype 6B (N= 137)	24.52 (20.48 to 29.35)
1 Month After 13vPnC Dose 2: Serotype 9V (N= 136)	7.46 (6.46 to 8.61)
1 Month After 13vPnC Dose 2: Serotype 14 (N = 137)	26.19 (22.11 to 31.03)
1 Month After 13vPnC Dose 2: Serotype 18C (N= 137)	5.44 (4.64 to 6.38)
1 Month After 13vPnC Dose 2: Serotype 19F (N= 136)	20.56 (17.15 to 24.63)
1 Month After 13vPnC Dose 2: Serotype 23F (N= 135)	16.18 (13.27 to 19.73)
1 Month After 13vPnC Dose 2: Serotype 1 (N = 137)	4.51 (3.82 to 5.32)
1 Month After 13vPnC Dose 2: Serotype 3 (N = 134)	1.67 (1.42 to 1.97)
1 Month After 13vPnC Dose 2: Serotype 5 (N = 136)	6.33 (5.58 to 7.17)
1 Month After 13vPnC Dose 2: Serotype 6A (N = 136)	16.37 (13.65 to 19.64)
1 Month After 13vPnC Dose 2: Serotype 7F (N = 137)	7.06 (6.2 to 8.04)
1 Month After 13vPnC Dose 2: Serotype 19A (N= 137)	22.19 (18.94 to 25.99)

Notes
[6] - Number of subjects analyzed signifies the evaluable immunogenicity population.

No statistical analyses for this end point

Secondary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Year After 13vPnC Dose 2

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End point title

Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Year After 13vPnC Dose 2

End point description

GMFR for the 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) are presented. GMC (13vPnC) and corresponding 2-sided 95 percent (%) CIs were evaluated. Geometric means were calculated using all subjects with available data for the specified blood draw. CI for GMC were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations. Analysis was done on the evaluable immunogenicity population at 1 year follow up- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. “N” signifies subjects with a determinate IgG antibody concentration for given serotype. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

1 year after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	81 ^[7]
Units: mcg/mL
geometric mean (confidence interval 95%)
Serotype 4 (N = 81)	1.94 (1.51 to 2.48)
Serotype 6B (N = 81)	11.77 (9.43 to 14.71)
Serotype 9V (N = 81)	4.5 (3.61 to 5.62)
Serotype 14 (N = 81)	15.89 (12.47 to 20.26)
Serotype 18C (N = 81)	2.64 (2.03 to 3.42)
Serotype 19F (N = 81)	9.87 (7.5 to 13)
Serotype 23F (N = 81)	7.7 (6.15 to 9.63)
Serotype 1 (N = 79)	2.12 (1.65 to 2.71)
Serotype 3 (N = 67)	1.01 (0.77 to 1.33)
Serotype 5 (N = 81)	4.38 (3.58 to 5.37)
Serotype 6A (N = 81)	7.94 (6.45 to 9.77)
Serotype 7F (N = 81)	3.47 (2.84 to 4.25)
Serotype 19A (N = 81)	13.3 (10.62 to 16.65)

Notes
[7] - Number of subjects analyzed signifies the evaluable immunogenicity population at 1-year follow-up.

No statistical analyses for this end point

Secondary: Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT)

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End point title

Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT)

End point description

Antibody GMTs as measured by OPA assay for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). GMT and corresponding 2-sided 95% CIs were evaluated. CIs for the GMTs are back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the titers. GMTs were calculated using all subjects with available data for the specified blood draw. Analysis was done on the evaluable immunogenicity population- eligible subjects who received all study vaccinations; had valid, determinate assay result; blood drawn within pre-specified time-frames; had no major protocol violation. "N" signifies subject with determinate OPA antibody titer for the given serotype at specified time point. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

Before 13vPnC Dose 1, 1 month after 13vPnC Dose 1, before 13vPnC Dose 2, 1 month after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	138 ^[8]
Units: Titer
geometric mean (confidence interval 95%)
Before 13vPnC Dose 1: Serotype 4 (N = 105)	215 (129.6 to 357.2)
Before 13vPnC Dose 1: Serotype 6B (N = 105)	626 (377.5 to 1037.4)
Before 13vPnC Dose 1: Serotype 9V (N = 109)	234 (137.6 to 398.7)
Before 13vPnC Dose 1: Serotype 14 (N = 115)	628 (425.8 to 925.7)
Before 13vPnC Dose 1: Serotype 18C (N = 95)	426 (235.7 to 771.4)
Before 13vPnC Dose 1: Serotype 19F (N = 96)	94 (55 to 160.7)
Before 13vPnC Dose 1: Serotype 23F (N = 106)	34 (21.5 to 54.8)
Before 13vPnC Dose 1: Serotype 1 (N = 131)	7 (5.7 to 8.8)
Before 13vPnC Dose 1: Serotype 3 (N = 107)	13 (10.1 to 17.5)
Before 13vPnC Dose 1: Serotype 5 (N = 131)	10 (7.8 to 13.9)
Before 13vPnC Dose 1: Serotype 6A (N = 116)	246 (149 to 404.8)
Before 13vPnC Dose 1: Serotype 7F (N = 120)	344 (220.5 to 537.9)
Before 13vPnC Dose 1: Serotype 19A (N = 127)	137 (100 to 187.4)
1 Month After 13vPnC Dose 1: Serotype 4 (N = 108)	2670 (2128.1 to 3351.1)
1 Month After 13vPnC Dose 1: Serotype 6B (N= 116)	7535 (6320.5 to 8983.5)
1 Month After 13vPnC Dose 1: Serotype 9V (N= 103)	2312 (1684 to 3172.8)
1 Month After 13vPnC Dose 1: Serotype 14 (N = 117)	2288 (1906.6 to 2745)
1 Month After 13vPnC Dose 1: Serotype 18C (N= 103)	4326 (3250.3 to 5756.8)
1 Month After 13vPnC Dose 1: Serotype 19F (N = 89)	1429 (1043.5 to 1957.3)
1 Month After 13vPnC Dose 1: Serotype 23F (N= 106)	1607 (1227.4 to 2102.7)
1 Month After 13vPnC Dose 1: Serotype 1 (N = 123)	56 (41 to 77.4)
1 Month After 13vPnC Dose 1: Serotype 3 (N = 112)	115 (93 to 142.1)
1 Month After 13vPnC Dose 1: Serotype 5 (N = 121)	277 (198.4 to 385.8)
1 Month After 13vPnC Dose 1: Serotype 6A (N = 117)	7845 (6581.6 to 9349.9)
1 Month After 13vPnC Dose 1: Serotype 7F (N = 123)	3348 (2881.9 to 3888.5)
1 Month After 13vPnC Dose 1: Serotype 19A (N =118)	1449 (1164.2 to 1804.3)
Before 13vPnC Dose 2: Serotype 4 (N = 104)	1331 (1013.9 to 1748.1)
Before 13vPnC Dose 2: Serotype 6B (N = 108)	4174 (3513 to 4958.3)
Before 13vPnC Dose 2: Serotype 9V (N = 99)	1445 (1051.7 to 1985.5)
Before 13vPnC Dose 2: Serotype 14 (N = 106)	1652 (1347.8 to 2024.1)
Before 13vPnC Dose 2: Serotype 18C (N = 101)	1928 (1281.1 to 2901)
Before 13vPnC Dose 2: Serotype 19F (N = 92)	516 (338.8 to 785.5)
Before 13vPnC Dose 2: Serotype 23F (N = 94)	897 (619 to 1300.4)
Before 13vPnC Dose 2: Serotype 1 (N = 107)	23 (17.1 to 32.3)
Before 13vPnC Dose 2: Serotype 3 (N = 120)	56 (45.5 to 69.9)
Before 13vPnC Dose 2: Serotype 5 (N = 107)	98 (69.2 to 140.2)
Before 13vPnC Dose 2: Serotype 6A (N = 113)	4005 (3350.6 to 4786.3)
Before 13vPnC Dose 2: Serotype 7F (N = 112)	1791 (1427 to 2248.6)
Before 13vPnC Dose 2: Serotype 19A (N = 108)	677 (544.4 to 843.1)
1 Month After 13vPnC Dose 2: Serotype 4 (N = 105)	3051 (2536.7 to 3670.3)
1 Month After 13vPnC Dose 2: Serotype 6B (N= 107)	7601 (6392.6 to 9038.6)
1 Month After 13vPnC Dose 2: Serotype 9V (N = 96)	3467 (2784 to 4317.6)
1 Month After 13vPnC Dose 2: Serotype 14 (N = 110)	2081 (1770.5 to 2446)
1 Month After 13vPnC Dose 2: Serotype 18C (N= 103)	5271 (4267.8 to 6510.1)
1 Month After 13vPnC Dose 2: Serotype 19F (N = 89)	1507 (1139.9 to 1992.2)
1 Month After 13vPnC Dose 2: Serotype 23F (N= 105)	2330 (1880.4 to 2887)
1 Month After 13vPnC Dose 2: Serotype 1 (N = 106)	78 (59.5 to 101.2)
1 Month After 13vPnC Dose 2: Serotype 3 (N = 109)	105 (87.2 to 127.2)
1 Month After 13vPnC Dose 2: Serotype 5 (N = 118)	273 (213.9 to 349.2)
1 Month After 13vPnC Dose 2: Serotype 6A (N = 111)	7633 (6439.6 to 9048.6)
1 Month After 13vPnC Dose 2: Serotype 7F (N = 114)	3723 (3276.2 to 4230.1)
1 Month After 13vPnC Dose 2: Serotype 19A (N= 115)	1314 (1084.4 to 1592.6)

Notes
[8] - Number of subjects analyzed signifies the evaluable immunogenicity population.

No statistical analyses for this end point

Secondary: Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Year After 13vPnC Dose 2

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End point title

Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Year After 13vPnC Dose 2

End point description

Antibody GMTs as measured by OPA assay for 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F). GMT and corresponding 2-sided 95% CIs were evaluated. CIs for the GMTs are back transformations of a confidence interval based on the Student t distribution for the mean logarithm of the titers. GMTs were calculated using all subjects with available data for the specified blood draw. Analysis was done on the evaluable immunogenicity population at 1-year follow up- eligible subjects who received all study vaccinations; had valid and determinate assay result; had blood drawn within pre-specified time-frames; had no major protocol violation. "N" signifies subjects with determinate OPA antibody titer for the given serotype. Subjects may be represented in more than 1 category.

End point type

Secondary

End point timeframe

1 year after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	81 ^[9]
Units: Titer
geometric mean (confidence interval 95%)
Serotype 4 (N = 58)	1107 (764.4 to 1602.2)
Serotype 6B (N = 59)	3412 (2746.4 to 4238.7)
Serotype 9V (N = 66)	1690 (1157.8 to 2465.5)
Serotype 14 (N = 64)	1595 (1281.6 to 1984.9)
Serotype 18C (N = 59)	1604 (1107.2 to 2324.2)
Serotype 19F (N = 55)	620 (376.6 to 1020.4)
Serotype 23F (N = 58)	924 (654.2 to 1306.1)
Serotype 1 (N = 73)	25 (17.5 to 35.4)
Serotype 3 (N = 72)	31 (22.6 to 42.6)
Serotype 5 (N = 71)	102 (70.5 to 148)
Serotype 6A (N = 72)	2485 (1921.2 to 3214.3)
Serotype 7F (N = 73)	2166 (1861.4 to 2519.3)
Serotype 19A (N = 73)	589 (449.4 to 771.1)

Notes
[9] - Number of subjects analyzed signifies the evaluable immunogenicity population at 1-year follow-up.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 1

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End point title

Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 1

End point description

Specific local reactions were prompted for each day using an electronic diary. Redness and Swelling were scaled as: Any (redness present or swelling present); Mild (less than [<]2.5 centimeters [cm] for subjects aged 6 to <12 years, 2.5 to 5.0 cm for subjects aged greater than or equal to [>=] 12 years); Moderate (2.5 to 7.0 cm for subjects aged 6 to <12 years and 5.1 to 10.0 cm for subjects aged >=12 years); Severe (>7 cm for subjects aged 6 to <12 years and >10 cm for subjects aged >=12 years). Pain was scaled as: Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity). Safety population Dose 1- all subjects who received Dose 1 of study vaccine, had safety dataavailable.“N” signifies those subjects who reported “Yes” for at least 1 day or “No” for for all days for specified local reaction. Subjects may be represented in more than 1 category.

End point type

Other pre-specified

End point timeframe

Within 7 days after 13vPnC Dose 1

End point values	13vPnC
Number of subjects analysed	158 ^[10]
Units: Percentage of subjects
number (not applicable)
Pain: Any (N = 144)	89.6
Pain: Mild (N = 132)	81.8
Pain: Moderate (N = 113)	56.6
Pain: Severe (N = 90)	11.1
Redness: Any (N = 93)	23.7
Redness: Mild (N = 93)	20.4
Redness: Moderate (N = 90)	8.9
Redness: Severe (N = 87)	1.1
Swelling: Any (N = 108)	49.1
Swelling: Mild (N = 101)	37.6
Swelling: Moderate (N = 100)	26
Swelling: Severe (N = 87)	1.1

Notes
[10] - Number of subjects analyzed signifies the safety population for Dose 1.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 2

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End point title

Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 2

End point description

Specific local reactions were prompted for each day using an electronic diary. Redness and Swelling were scaled as: Any (redness present or swelling present); Mild (less than <2.5 centimeters [cm] for subjects aged 6 to <12 years, 2.5 to 5.0 cm for subjects aged >= 12 years); Moderate (2.5 to 7.0 cm for subjects aged 6 to <12 years and 5.1 to 10.0 cm for subjects aged >=12 years); Severe (>7 cm for subjects aged 6 to <12 years and >10 cm for subjects aged >=12 years). Pain was scaled as: Any (pain present); Mild (did not interfere with activity); Moderate (interfered with activity); Severe (prevented daily activity). Safety population Dose 2- all subjects who received Dose 2 of study vaccine and had safety data available. “N” signifies those subjects who reported “Yes” for at least 1 day or “No” for for all days for specified local reaction. Subject may be represented in more than 1 category.

End point type

Other pre-specified

End point timeframe

Within 7 days after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	140 ^[11]
Units: Percentage of subjects
number (not applicable)
Pain: Any (N = 111)	85.6
Pain: Mild (N = 103)	77.7
Pain: Moderate (N = 82)	53.7
Pain: Severe (N = 69)	15.9
Redness: Any (N = 67)	26.9
Redness: Mild (N = 66)	15.2
Redness: Moderate (N = 64)	14.1
Redness: Severe (N = 63)	0
Swelling: Any (N = 84)	53.6
Swelling: Mild (N = 77)	37.7
Swelling: Moderate (N = 73)	35.6
Swelling: Severe (N = 63)	0

Notes
[11] - Number of subjects analyzed signifies the safety population for Dose 2.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 1

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End point title

Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 1

End point description

Specific systemic events (fever >=38 degrees Celsius[C], vomiting, diarrhea, headache, fatigue, muscle pain, joint pain, use of antipyretic medications) were reported for each day using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any(symptom present); Mild(did not interfere with activity); Moderate(some interference); Severe(prevented routine daily activity). Vomiting was scaled as: Any(vomiting present); Mild(1-2 times in 24 hours); Moderate(>2 times in 24 hours); Severe(required intravenous hydration). Diarrhea was scaled as: Any(diarrhea present); Mild(2-3 loose stools in 24 hours);Moderate(4-5 loose stools 24 hours); Severe(>=6 loose stools in 24 hours). Safety population Dose 1- all subjects who received Dose 1 of study vaccine, had safety data available. “N” signifies those subjects who reported “Yes” for at least 1 day or “No” for for all days for specified local reaction. Subjects may be represented in more than 1 category.

End point type

Other pre-specified

End point timeframe

Within 7 days after 13vPnC Dose 1

End point values	13vPnC
Number of subjects analysed	158 ^[12]
Units: Percentage of subjects
number (not applicable)
Fever: >=38, =<38.4 degrees C (N = 81)	13.6
Fever: >38.4, =<38.9 degrees C (N = 82)	7.3
Fever: >38.9, =<40 degrees C (N = 79)	3.8
Fever: >40 degrees C (N = 79)	1.3
Vomiting: Any (N = 91)	15.4
Vomiting: Mild (N = 89)	11.2
Vomiting: Moderate (N = 90)	6.7
Vomiting: Severe (N = 87)	0
Diarrhea: Any (N = 90)	13.3
Diarrhea: Mild (N = 87)	6.9
Diarrhea: Moderate (N = 90)	6.7
Diarrhea: Severe (N = 87)	2.3
Headache: Any (N = 110)	53.6
Headache: Mild (N = 105)	42.9
Headache: Moderate (N = 101)	34.7
Headache: Severe (N = 92)	12
Fatigue: Any (N = 118)	66.1
Fatigue: Mild (N = 108)	48.1
Fatigue: Moderate (N = 104)	44.2
Fatigue: Severe (N = 90)	14.4
Muscle Pain: Any (N = 127)	74.8
Muscle Pain: Mild (N = 114)	58.8
Muscle Pain: Moderate (N = 108)	47.2
Muscle Pain: Severe (N = 89)	10.1
Joint Pain: Any (N = 103)	39.8
Joint Pain: Mild (N = 98)	23.5
Joint Pain: Moderate (N = 94)	23.4
Joint Pain: Severe (N = 89)	4.5
Use of Antipyretic Medications (N = 110)	58.2

Notes
[12] - Number of subjects analyzed signifies the safety population for Dose 1.

No statistical analyses for this end point

Other pre-specified: Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 2

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End point title

Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 2

End point description

Specific systemic events (fever >=38 degrees Celsius[C], vomiting, diarrhea, headache, fatigue, muscle pain, joint pain, use of antipyretic medications) were reported for each day using an electronic diary. Fatigue, headache, muscle pain and joint pain were scaled as: Any(symptom present); Mild(did not interfere with activity); Moderate(some interference); Severe(prevented routine daily activity). Vomiting was scaled as: Any(vomiting present); Mild(1-2 times in 24 hours); Moderate(>2 times in 24 hours); Severe(required intravenous hydration). Diarrhea was scaled as: Any(diarrhea present); Mild(2-3 loose stools in 24 hours);Moderate(4-5 loose stools 24 hours); Severe(>=6 loose stools in 24 hours). Safety population Dose 2- all subjects who received Dose 2 of study vaccine, had safety data available. “N” signifies those subjects who reported “Yes” for at least 1 day or “No” for for all days for specified local reaction. Subjects may be represented in more than 1 category.

End point type

Other pre-specified

End point timeframe

Within 7 days after 13vPnC Dose 2

End point values	13vPnC
Number of subjects analysed	140 ^[13]
Units: Percentage of subjects
number (not applicable)
Fever: >=38, =<38.4 degrees C (N = 63)	9.5
Fever: >38.4, =<38.9 degrees C (N = 59)	6.8
Fever: >38.9, =<40 degrees C (N = 63)	6.3
Fever: >40 degrees C (N = 60)	1.7
Vomiting: Any (N = 67)	13.4
Vomiting: Mild (N = 65)	9.2
Vomiting: Moderate (N = 64)	4.7
Vomiting: Severe (N = 64)	1.6
Diarrhea: Any (N = 68)	25
Diarrhea: Mild (N = 68)	19.1
Diarrhea: Moderate (N = 66)	12.1
Diarrhea: Severe (N = 63)	3.2
Headache: Any (N = 86)	59.3
Headache: Mild (N = 74)	41.9
Headache: Moderate (N = 76)	36.8
Headache: Severe (N = 66)	10.6
Fatigue: Any (N = 96)	62.5
Fatigue: Mild (N = 84)	48.8
Fatigue: Moderate (N = 83)	41
Fatigue: Severe (N = 67)	13.4
Muscle Pain: Any (N = 98)	75.5
Muscle Pain: Mild (N = 87)	60.9
Muscle Pain: Moderate (N = 84)	45.2
Muscle Pain: Severe (N = 67)	16.4
Joint Pain: Any (N = 78)	44.9
Joint Pain: Mild (N = 72)	34.7
Joint Pain: Moderate (N = 70)	21.4
Joint Pain: Severe (N = 65)	6.2
Use of Antipyretic Medications (N = 78)	43.6

Notes
[13] - Number of subjects analyzed signifies the safety population for Dose 2.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs: Baseline up to 1 year after Dose 2. AEs: 1 month after each 13vPnC dose. Newly diagnosed chronic medical conditions: 6 months after each 13vPnC dose, at 1 year after 13vPnC Dose 2. Local reactions/systemic events: within 7 days after each dose

Adverse event reporting additional description

Safety population: subjects who received at least 1 dose and had safety data available. AEs included events collected in electronic diary (systematic assessment for local reactions [LR] and systemic events [SE]) and events collected on case report form at each visit (non systematic assessment for SAEs and non-SAEs).

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

13vPnC Dose 1

Reporting group description

Subjects previously immunized with 23vPS who received a single 0.5 mL dose of 13vPnC intramuscular injection on Day 1 (13vPnC Dose 1), assessed between 13vPnC Dose 1 and before 13vPnC Dose2.

Reporting group title

13vPnC Dose 2

Reporting group description

Subjects previously immunized with 23vPS who received Dose 2 of 0.5 mL 13vPnC intramuscular injection, assessed between 13vPnC Dose 2 and before 13vPnC Dose 2 blood draw.

Reporting group title

6-Month Follow-up

Reporting group description

Subjects previously immunized with 23vPS who received at least 1 of the 2 single 0.5 mL doses of 13vPnC intramuscular injection, 6 months apart, assessed from last 13vPnC Dose (Dose 1 or Dose 2) blood draw to the 6-month follow-up telephone contact.

Reporting group title

1-Year Follow-up

Reporting group description

Subjects previously immunized with 23vPS who received 2 single 0.5 mL doses of 13vPnC intramuscular injection, 6 months apart, assessed from the 6-month follow-up telephone contact after 13vPnC Dose 2 to the 1-year follow-up after 13vPnC Dose 2.

Serious adverse events	13vPnC Dose 1	13vPnC Dose 2	6-Month Follow-up	1-Year Follow-up
Total subjects affected by serious adverse events
subjects affected / exposed	40 / 158 (25.32%)	11 / 140 (7.86%)	28 / 147 (19.05%)	16 / 87 (18.39%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Vascular disorders
Vascular occlusion
subjects affected / exposed	3 / 158 (1.90%)	2 / 140 (1.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Pregnancy
subjects affected / exposed	0 / 158 (0.00%)	2 / 140 (1.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 158 (3.16%)	0 / 140 (0.00%)	2 / 147 (1.36%)	3 / 87 (3.45%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	2 / 147 (1.36%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Priapism
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome
subjects affected / exposed	3 / 158 (1.90%)	0 / 140 (0.00%)	2 / 147 (1.36%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	1 / 147 (0.68%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung infiltration
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Overdose
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
subjects affected / exposed	22 / 158 (13.92%)	5 / 140 (3.57%)	17 / 147 (11.56%)	11 / 87 (12.64%)
occurrences causally related to treatment / all	0 / 30	0 / 6	0 / 25	0 / 17
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Unresponsive to stimuli
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lethargy
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Migraine
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemolytic anaemia
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypersplenism
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Visual impairment
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gingivitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Haematuria
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure chronic
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysuria
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Flank pain
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	1 / 158 (0.63%)	2 / 140 (1.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in jaw
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	2 / 147 (1.36%)	4 / 87 (4.60%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone abscess
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	1 / 147 (0.68%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis A
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypocalcaemia
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	13vPnC Dose 1	13vPnC Dose 2	6-Month Follow-up	1-Year Follow-up
Total subjects affected by non serious adverse events
subjects affected / exposed	133 / 158 (84.18%)	100 / 140 (71.43%)	1 / 147 (0.68%)	1 / 87 (1.15%)
Vascular disorders
Vascular occlusion
subjects affected / exposed	4 / 158 (2.53%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	5	0	0	0
Hypertension
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
General disorders and administration site conditions
Injection site swelling
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Pain
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Pyrexia
subjects affected / exposed	5 / 158 (3.16%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	5	1	0	0
Chest pain
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Injection site pain
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Asthenia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Injection site erythema
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Injection site movement impairment
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Oedema peripheral
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Swelling
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Fever ≥38°C but ≤38.4°C
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[1]	11 / 81 (13.58%)	6 / 63 (9.52%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	11	6	0	0
Fever >38.4°C but ≤38.9°C
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[2]	6 / 82 (7.32%)	4 / 59 (6.78%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	6	4	0	0
Fever >38.9°C but ≤40.0°C
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[3]	3 / 79 (3.80%)	4 / 63 (6.35%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	3	4	0	0
Fever >40.0°C
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[4]	1 / 79 (1.27%)	1 / 60 (1.67%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	1	0	0
Vomiting (Any)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[5]	14 / 91 (15.38%)	9 / 67 (13.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	14	9	0	0
Vomiting (Mild)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[6]	10 / 89 (11.24%)	6 / 65 (9.23%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	10	6	0	0
Vomiting (Moderate)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[7]	6 / 90 (6.67%)	3 / 64 (4.69%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	6	3	0	0
Vomiting (Severe)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[8]	0 / 87 (0.00%)	1 / 64 (1.56%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Diarrhea (Any)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[9]	12 / 90 (13.33%)	17 / 68 (25.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	12	17	0	0
Diarrhea (Mild)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[10]	6 / 87 (6.90%)	13 / 68 (19.12%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	6	13	0	0
Diarrhea (Moderate)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[11]	6 / 90 (6.67%)	8 / 66 (12.12%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	6	8	0	0
Diarrhea (Severe)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[12]	2 / 87 (2.30%)	2 / 63 (3.17%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	2	0	0
Headache (Any)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[13]	59 / 110 (53.64%)	51 / 86 (59.30%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	59	51	0	0
Headache (Mild)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[14]	45 / 105 (42.86%)	31 / 74 (41.89%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	45	31	0	0
Headache (Moderate)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[15]	35 / 101 (34.65%)	28 / 76 (36.84%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	35	28	0	0
Headache (Severe)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[16]	11 / 92 (11.96%)	7 / 66 (10.61%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	11	7	0	0
Fatigue (Mild)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[17]	52 / 108 (48.15%)	41 / 84 (48.81%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	52	41	0	0
Fatigue (Moderate)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[18]	46 / 104 (44.23%)	34 / 83 (40.96%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	46	34	0	0
Fatigue (Severe)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[19]	13 / 90 (14.44%)	9 / 67 (13.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	13	9	0	0
Muscle pain (Any)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[20]	95 / 127 (74.80%)	74 / 98 (75.51%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	95	74	0	0
Muscle pain (Mild)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[21]	67 / 114 (58.77%)	53 / 87 (60.92%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	67	53	0	0
Muscle pain (Moderate)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[22]	51 / 108 (47.22%)	38 / 84 (45.24%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	51	38	0	0
Muscle pain (Severe)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[23]	9 / 89 (10.11%)	11 / 67 (16.42%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	9	11	0	0
Joint pain (Any)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[24]	41 / 103 (39.81%)	35 / 78 (44.87%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	41	35	0	0
Joint pain (Mild)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[25]	23 / 98 (23.47%)	25 / 72 (34.72%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	23	25	0	0
Joint pain (Moderate)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[26]	22 / 94 (23.40%)	15 / 70 (21.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	22	15	0	0
Joint pain (Severe)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[27]	4 / 89 (4.49%)	4 / 65 (6.15%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	4	4	0	0
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	1 / 147 (0.68%)	0 / 87 (0.00%)
occurrences all number	0	0	1	0
Productive cough
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Cough
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Oropharyngeal pain
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Rhinorrhoea
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Epistaxis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Haemoptysis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Nasal congestion
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Psychiatric disorders
Listless
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Depression
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Insomnia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Injury, poisoning and procedural complications
Transfusion reaction
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Congenital, familial and genetic disorders
Sickle cell anaemia with crisis
subjects affected / exposed	4 / 158 (2.53%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	4	1	0	0
Nervous system disorders
Headache
subjects affected / exposed	4 / 158 (2.53%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	4	1	0	0
Convulsion
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Hypoaesthesia
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Moyamoya disease
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Ocular icterus
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Periorbital oedema
subjects affected / exposed	1 / 158 (0.63%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	1	0	0
Conjunctivitis allergic
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Hiatus hernia
subjects affected / exposed	0 / 158 (0.00%)	0 / 140 (0.00%)	0 / 147 (0.00%)	1 / 87 (1.15%)
occurrences all number	0	0	0	1
Abdominal pain
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Gingival pain
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Oral pain
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Diarrhoea
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Vomiting
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Abdominal pain upper
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Constipation
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Nausea
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Pancreatic calcification
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Fatigue (Any)
Additional description: Subjects affected and occurrences for SE is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Systemic Events 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[28]	78 / 118 (66.10%)	60 / 96 (62.50%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	78	60	0	0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Skin and subcutaneous tissue disorders
Swelling face
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Pain (Any)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[29]	129 / 144 (89.58%)	95 / 111 (85.59%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	129	95	0	0
Pain (Mild)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[30]	108 / 132 (81.82%)	80 / 103 (77.67%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	108	80	0	0
Pain (Moderate)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[31]	64 / 113 (56.64%)	44 / 82 (53.66%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	64	44	0	0
Pain (Severe)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[32]	10 / 90 (11.11%)	11 / 69 (15.94%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	10	11	0	0
Redness (Any)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[33]	22 / 93 (23.66%)	18 / 67 (26.87%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	22	18	0	0
Redness (Mild)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[34]	19 / 93 (20.43%)	10 / 66 (15.15%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	19	10	0	0
Redness (Moderate)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[35]	8 / 90 (8.89%)	9 / 64 (14.06%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	8	9	0	0
Redness (Severe)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[36]	1 / 87 (1.15%)	0 / 63 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Swelling (Any)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[37]	53 / 108 (49.07%)	45 / 84 (53.57%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	53	45	0	0
Swelling (Mild)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[38]	38 / 101 (37.62%)	29 / 77 (37.66%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	38	29	0	0
Swelling (Moderate)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[39]	26 / 100 (26.00%)	26 / 73 (35.62%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	26	26	0	0
Swelling (Severe)
Additional description: Subjects affected and occurrences for LR is same as data collected through ediaries cannot be used to distinguish one occurrence from another within a subject/vaccination.
alternative dictionary used: Local Reactions 0.0
alternative assessment type: Systematic
subjects affected / exposed ^[40]	1 / 87 (1.15%)	0 / 63 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Renal and urinary disorders
Renal failure chronic
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	2 / 158 (1.27%)	2 / 140 (1.43%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	3	0	0
Arthralgia
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Back pain
subjects affected / exposed	1 / 158 (0.63%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	1	0	0
Joint swelling
subjects affected / exposed	0 / 158 (0.00%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal chest pain
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Infections and infestations
Pharyngitis
subjects affected / exposed	1 / 158 (0.63%)	1 / 140 (0.71%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	1	0	0
Nasopharyngitis
subjects affected / exposed	2 / 158 (1.27%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	2	0	0	0
Infection
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Rhinitis
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 158 (0.63%)	0 / 140 (0.00%)	0 / 147 (0.00%)	0 / 87 (0.00%)
occurrences all number	1	0	0	0

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

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine in Children With Sickle Cell Disease Previously Immunized With 23-valent Pneumococcal Polysaccharide Vaccine

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 1 Month After 13vPnC Dose 1 to 1 Month After 13vPnC Dose 2

Primary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 1 Month After 13vPnC Dose 1 to 1 Month After 13vPnC Dose 2

Secondary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1

Secondary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 1 to 1 Month After 13vPnC Dose 1

Secondary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 2 to 1 Month After 13vPnC Dose 2

Secondary: Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From Before 13vPnC Dose 2 to 1 Month After 13vPnC Dose 2

Secondary: Ratio of Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 13vPnC Dose 1 to 13vPnC Dose 2

Secondary: Ratio of Geometric Mean Fold Rise (GMFR) in Serotype-Specific Pneumococcal Immunoglobulin G (IgG) From 13vPnC Dose 1 to 13vPnC Dose 2

Secondary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody

Secondary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody

Secondary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Year After 13vPnC Dose 2

Secondary: Geometric Mean Concentration (GMC) for Serotype-Specific Pneumococcal Immunoglobulin G (IgG) Antibody 1 Year After 13vPnC Dose 2

Secondary: Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT)

Secondary: Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT)

Secondary: Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Year After 13vPnC Dose 2

Secondary: Serotype-Specific Pneumococcal Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMT) 1 Year After 13vPnC Dose 2

Other pre-specified: Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 1

Other pre-specified: Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 1

Other pre-specified: Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 2

Other pre-specified: Percentage of Subjects With Prespecified Local Reactions: 13vPnC Dose 2

Other pre-specified: Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 1

Other pre-specified: Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 1

Other pre-specified: Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 2

Other pre-specified: Percentage of Subjects With Prespecified Systemic Events: 13vPnC Dose 2

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Open-label, Single-Arm Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 13-valent Pneumococcal Conjugate Vaccine in Children With Sickle Cell Disease Previously Immunized With 23-valent Pneumococcal Polysaccharide Vaccine