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Clinical Trial Results:
A phase III/IV, cluster-randomized, controlled study to evaluate the effectiveness of GlaxoSmithKline Biologicals’ 10-valent pneumococcal and non-typeable Haemophilus influenzae protein D conjugate vaccine in reducing the incidence of invasive diseases.

Summary
EudraCT number	2008-005149-48
Trial protocol	FI
Global end of trial date	05 Oct 2013

Results information
Results version number	v1
This version publication date	16 Feb 2016
First version publication date	29 Jul 2015
Other versions	v2 , v3 , v4

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

111442

ISRCTN number

US NCT number

NCT00861380

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, B-1330, Belgium, Rixensart, Belgium, B-1330

Public contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000673-PIP01-09

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

22 Apr 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Oct 2013

Was the trial ended prematurely?

Main objective of the trial

To demonstrate the effectiveness of 10Pn-PD-DiT vaccine in preventing culture-confirmed IPD due to vaccine pneumococcal serotypes in children vaccinated with at least one dose of 10Pn-PD-DiT within the first 7 months of life in clusters assigned to a 3-dose primary vaccination course. Criteria for effectiveness: Effectiveness (VE) in preventing culture-confirmed IPD due to the 10 vaccine serotypes will be demonstrated if the 2-sided p-value calculated for the null hypothesis H0 = {vaccine-type [VT] IPD VE = 0%} is lower than 5%.

Protection of trial subjects

The nurses administering vaccines were instructed to observe the vaccinees closely for at least 30 minutes following the administration of vaccines, with appropriate medical treatment readily available in case of a rare anaphylactic reaction. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were followed up for serious adverse events (SAEs) reported as occurring during the study up to study end. In addition, an Independent Data Monitoring Committee (IDMC) was set up, of which responsibilities included the following: (1) Review of data collection methods, safety/effectiveness monitoring procedures and making recommendations for additions or adjustments, as applicable; (2) Recommendations for maintaining, or breaking the blind where necessary, in the course of reviewing safety results; (3) Recommendations for stopping the trial for effectiveness or safety reasons when appropriate.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 May 2009

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

18 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Finland: 2695198

Worldwide total number of subjects

2695198

EEA total number of subjects

2695198

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)

41188

Children (2-11 years)

530802

Adolescents (12-17 years)

530802

Adults (18-64 years)

530802

From 65 to 84 years

530802

85 years and over

530802

Subject disposition

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Recruitment details

This study is linked with 10PN-PD-DIT-053 (112595) study (EudraCT: 2008-006551-51) with which primary objectives and endpoints are common. +/- 6000 subjects in 10PN-PD-DIT-053 study contributed to primary objectives and endpoints results of this 10PN-PD-DIT-043 study as well as some secondary efficacy and safety analyses.

Screening details

Screening involved: check on inclusion/exclusion criteria & medical history, randomization, signing of informed consent forms by subjects’ parent(s)/legally accepted representative(s) (LAR[s]) & check for enrolment of control unvaccinated subjects towards indirect effect analysis (up to maximum 2626735 subjects per year of analysis were assessed).

Number of subjects started

2695198

Number of subjects completed

41181

Reason: Number of subjects

Unvaccinated subject enrolled for Indirect effect: 2654010

Reason: Number of subjects

Subject not vaccinated: 7

Period 1 title

Entire Study Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

10Pn3+1-6W-6M/043 Group

Arm description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.

Arm type

Experimental

Investigational medicinal product name

10-valent pneumococcal and non-typeable H. influenzae protein D conjugate vaccine

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh.

10Pn2+1-6W-6M/043 Group

Arm description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.

Arm type

Experimental

Investigational medicinal product name

10-valent pneumococcal and non-typeable H. influenzae protein D conjugate vaccine

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh.

Ctrl-6W-6M/043 Group

Arm description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.

Arm type

Active comparator

Investigational medicinal product name

Engerix B-thio free

Investigational medicinal product code

Other name

Engerix-B,HBV

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh.

10PN 7-11M/111442 Group

Arm description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 7 to 11 months at enrolment. Subjects received the Engerix B-thio free (or HBV) vaccine according to either a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh.

Arm type

Experimental

Investigational medicinal product name

10-valent pneumococcal and non-typeable H. influenzae protein D conjugate vaccine

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh.

Ctrl7-11M/043 Group

Arm description

Arm type

Active comparator

Investigational medicinal product name

Engerix B-thio free

Investigational medicinal product code

Other name

Engerix-B,HBV

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh.

10Pn12-18M/043 Group

Arm description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 12 to 18 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.

Arm type

Experimental

Investigational medicinal product name

10-valent pneumococcal and non-typeable H. influenzae protein D conjugate vaccine

Investigational medicinal product code

10Pn-PD-DiT

Other name

10Pn, Synflorix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.

Ctrl12-18M/043 Group

Arm description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 12 to 18 months at enrolment. Subjects received the Havrix-preservative free (or HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.

Arm type

Active comparator

Investigational medicinal product name

Havrix-preservative free

Investigational medicinal product code

Other name

HAV, Havrix 720 Junior

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscularly administration by injection in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.

Number of subjects in period 1 ^[1]	10Pn3+1-6W-6M/043 Group	10Pn2+1-6W-6M/043 Group	Ctrl-6W-6M/043 Group	10PN 7-11M/111442 Group	Ctrl7-11M/043 Group	10Pn12-18M/043 Group	Ctrl12-18M/043 Group
Started	8427	9112	8872	3689	1812	6249	3020
Completed	0	0	0	0	0	0	0
Not completed	8427	9112	8872	3689	1812	6249	3020
Withdrawal Information not recorded	8427	9112	8872	3689	1812	6249	3020

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Including unvaccinated subjects enrolled for indirect effect analysis (including results to year 2012 only), a total of 2695198 subjects were enrolled in the study. Out of these, 41188 were planned to be vaccinated. 41181 of these were actually vaccinated and included in baseline period for the study.

Baseline characteristics

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Reporting group title

10Pn3+1-6W-6M/043 Group

Reporting group description

Reporting group title

10Pn2+1-6W-6M/043 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.

Reporting group title

Ctrl-6W-6M/043 Group

Reporting group description

Reporting group title

10PN 7-11M/111442 Group

Reporting group description

Reporting group title

Ctrl7-11M/043 Group

Reporting group description

Reporting group title

10Pn12-18M/043 Group

Reporting group description

Reporting group title

Ctrl12-18M/043 Group

Reporting group description

Reporting group values	10Pn3+1-6W-6M/043 Group	10Pn2+1-6W-6M/043 Group	Ctrl-6W-6M/043 Group	10PN 7-11M/111442 Group	Ctrl7-11M/043 Group	10Pn12-18M/043 Group	Ctrl12-18M/043 Group	Total
Number of subjects	8427	9112	8872	3689	1812	6249	3020	41181
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	8427	9112	8872	0	0	0	0	26411
Children (2-11 years)	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0
Not recorded	0	0	0	3689	1812	6249	3020	14770
Gender categorical
Units: Subjects
Female	4239	4399	4351	0	0	0	0	12989
Male	4188	4713	4521	0	0	0	0	13422
Not recorded	0	0	0	3689	1812	6249	3020	14770

End points

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Reporting group title

10Pn3+1-6W-6M/043 Group

Reporting group description

Reporting group title

10Pn2+1-6W-6M/043 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.

Reporting group title

Ctrl-6W-6M/043 Group

Reporting group description

Reporting group title

10PN 7-11M/111442 Group

Reporting group description

Reporting group title

Ctrl7-11M/043 Group

Reporting group description

Reporting group title

10Pn12-18M/043 Group

Reporting group description

Reporting group title

Ctrl12-18M/043 Group

Reporting group description

Subject analysis set title

10Pn3+1-6W-6M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

10Pn2+1-6W-6M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Ctrl-6W-6M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

10Pn7-11M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to either a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

Ctrl7-11M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B-thio free (or HBV) vaccine according to either a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

10Pn12-18M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

Ctrl12-18M/043+053 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

Ctrl3+1-6W-6M/043 Group

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

Ctrl2+1-6W-6M/043 Group

Subject analysis set type

Safety analysis

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Subject analysis set title

Ind-10Pn/043+053 Y2010 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, aged 5 years and above at enrolment, who were unvaccinated in the civil year 2010 (1st January to 31st December 2010) with the 10Pn vaccine and who lived in the study cluster areas, in which study participants received 10Pn vaccine.

Subject analysis set title

Ind-Ctrl/043+053 Y2010 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, aged 5 years and above at enrolment, who were unvaccinated in the civil year 2010 (1st January to 31st December 2010) with the HBV or HAV vaccine and who lived in the study cluster areas, in which study participants received HBV or HAV vaccine.

Subject analysis set title

Ind-10Pn/043+053 Y2011 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, aged 5 years and above at enrolment, who were unvaccinated in the civil year 2011 (1st January to 31st December 2011) with the 10Pn vaccine and who lived in the study cluster areas, in which study participants received 10Pn vaccine.

Subject analysis set title

Ind-Ctrl/043+053 Y2011 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, aged 5 years and above at enrolment, who were unvaccinated in the civil year 2011 (1st January to 31st December 2011) with the HBV or HAV vaccine and who lived in the study cluster areas, in which study participants received HBV or HAV vaccine.

Subject analysis set title

Ind-10Pn/043+053 Y2012 Group

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Ind-Ctrl/043+053 Y2012 Group

Subject analysis set type

Per protocol

Subject analysis set description

Primary: PYAR as regards subjects with culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.

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End point title

PYAR as regards subjects with culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.

End point description

The PYAR (Person-Year Rate) as regards subjects with culture-confirmed invasive pneumococcal disease (IPD) due to any of the pneumococcal vaccine serotypes was tabulated (vaccine pneumococcal serotypes = serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). PYAR was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.

End point type

Primary

End point timeframe

Period of follow-up was anytime after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period.

End point values	10Pn3+1-6W-6M/043+053 Group	Ctrl-6W-6M/043+053 Group
Number of subjects analysed	10273	10201
Units: PYAR
arithmetic mean (confidence interval 95%)
PYAR IPD Pneumococcal	0 (0 to 1.172)	0.564 (0.291 to 0.984)

VE at preventing culture-confirmed IPD

Statistical analysis description

The analysis aimed at providing an estimate of vaccine effectiveness (VE) at preventing culture-confirmed IPD by comparing PYARs between groups taking into account the following parameters: T, n, n+ (number of clusters with at least one event culture-confirmed ID), and n/T. VE of the 10Pn vaccine in preventing culture-confirmed IPD due to the 10 vaccine serotypes was demonstrated if the 2-sided p-value calculated for the null hypothesis H0 = (vaccine-type [VT] IPD VE = 0%) was lower than (<) 5%.

Comparison groups

10Pn3+1-6W-6M/043+053 Group v Ctrl-6W-6M/043+053 Group

Number of subjects included in analysis

20474

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.0001 ^[2]

Method

Regression, Linear

Parameter type

VE (1-RR)

Point estimate

100

Confidence interval

level

95%

sides

2-sided

lower limit

82.8

upper limit

100

Notes
[1] - VE (defined as 1 minus Relative Risk (RR)) was calculated by comparing numbers of culture-confirmed IPD. The number of subjects with IPD in each cluster was compared between groups (10PN3+1 vs Control). This comparison was done using a negative binomial log-linear model with correction for dispersion group- and cluster-related effect. Over-dispersion being assessed was null, a standard Poisson model methodology was applied including the group and cluster stratification factors as covariates.
[2] - p-value was calculated using a classical log linear Poisson regression with strata, without taking into account the multiplicity of the endpoints.

Adverse events

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Timeframe for reporting adverse events

Only SAEs were collected, based on 2 follow-up (FU) periods. First period assessed is from Month 0 to end of blinded invasive disease (ID) FU phase (31 Jan 2012), in 10PN-PD-DIT-043 subjects only, Events collected from this period are marked “M0-IDFU”

Adverse event reporting additional description

Second period of assessment from the end of blinded ID FU phase to study end in 10PN-PD-DIT-043 study, 05 October 2013. Events from this period of assessment are marked “IDFU-SE” The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

10Pn2+1-6W-6M/043 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.

Reporting group title

Ctrl2+1-6W-6M/043 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Reporting group title

10Pn3+1-6W-6M/043 Group

Reporting group description

Reporting group title

Ctrl3+1-6W-6M/043 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Reporting group title

10Pn7-11M/043 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) study only and aged 7 to 11 months at enrolment. Subjects received the Synflorix (or 10Pn-PD-DiT, or 10Pn) vaccine according to either a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh.

Reporting group title

Ctrl7-11M/043 Group

Reporting group description

Reporting group title

10Pn12-18M/043 Group

Reporting group description

Reporting group title

Ctrl12-18M/043 Group

Reporting group description

Reporting group title

10Pn3+1-6W-6M/043+053 Group

Reporting group description

Reporting group title

10Pn2+1-6W-6M/043+053 Group

Reporting group description

Reporting group title

Ctrl-6W-6M/043+053 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B-thio free vaccine (or HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for details on vaccine specifics and administration route in this group.

Reporting group title

10Pn7-11M/043+053 Group

Reporting group description

Reporting group title

Ctrl7-11M/043+053 Group

Reporting group description

Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (111442) and 10PN-PD-DIT (112595) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B-thio free (or HBV) vaccine according to either a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for details on vaccine specifics and administration route in this group.

Reporting group title

10Pn12-18M/043+053 Group

Reporting group description

Reporting group title

Ctrl12-18M/043+053 Group

Reporting group description

Notes
[1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
Justification: Only SAEs events were collected as part of this study.

10Pn2+1-6W-6M/043 Group

Ctrl2+1-6W-6M/043 Group

10Pn3+1-6W-6M/043 Group

Ctrl3+1-6W-6M/043 Group

10Pn7-11M/043 Group

Ctrl7-11M/043 Group

10Pn12-18M/043 Group

Ctrl12-18M/043 Group

10Pn3+1-6W-6M/043+053 Group

10Pn2+1-6W-6M/043+053 Group

Ctrl-6W-6M/043+053 Group

10Pn7-11M/043+053 Group

Ctrl7-11M/043+053 Group

10Pn12-18M/043+053 Group

Ctrl12-18M/043+053 Group

Total subjects affected by serious adverse events

subjects affected / exposed

7 / 9112 (0.08%)

1 / 4399 (0.02%)

6 / 8427 (0.07%)

7 / 4473 (0.16%)

3 / 3689 (0.08%)

2 / 1812 (0.11%)

2 / 6249 (0.03%)

2 / 3020 (0.07%)

1 / 10273 (0.01%)

1 / 10054 (0.01%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

1 / 6535 (0.02%)

0 / 3126 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Foreign body M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Road traffic accident M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Gaucher’s disease M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Krabbe’s disease M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Quadriplegic infantile cerebral palsy IDFU-SE

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

1 / 10054 (0.01%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Kawasaki’s disease M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

1 / 3689 (0.03%)

0 / 1812 (0.00%)

1 / 6249 (0.02%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Myocarditis M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Nervous system disorders

Convulsion M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

1 / 1812 (0.06%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile convulsion M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

1 / 3689 (0.03%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

1 / 3020 (0.03%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

1 / 1812 (0.06%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotonic-hyporesponsive episode M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epilepsy IDFU-SE

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

1 / 10273 (0.01%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Accidental death M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Death M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Injection site reaction M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Irritability M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

2 / 8427 (0.02%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Sudden death M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Sudden infant death syndrome M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Eye disorders

Optic atrophy IDFU-SE

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

1 / 10054 (0.01%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Diarrhoea M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea haemorrhagic M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

1 / 6249 (0.02%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Reye’s syndrome M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Respiratory, thoracic and mediastinal disorders

Asphyxia M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

1 / 3020 (0.03%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Skin and subcutaneous tissue disorders

Eczema M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Cystitis M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infection M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

1 / 4399 (0.02%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngitis M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Parotitis M0-ID FU

subjects affected / exposed

1 / 9112 (0.01%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumococcal sepsis M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

1 / 4473 (0.02%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

1 / 8427 (0.01%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Tonsillitis M0-ID FU

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

1 / 3689 (0.03%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumococcal infection IDFU-SE

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

1 / 6535 (0.02%)

0 / 3126 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

10Pn2+1-6W-6M/043 Group

Ctrl2+1-6W-6M/043 Group

10Pn3+1-6W-6M/043 Group

Ctrl3+1-6W-6M/043 Group

10Pn7-11M/043 Group

Ctrl7-11M/043 Group

10Pn12-18M/043 Group

Ctrl12-18M/043 Group

10Pn3+1-6W-6M/043+053 Group

10Pn2+1-6W-6M/043+053 Group

Ctrl-6W-6M/043+053 Group

10Pn7-11M/043+053 Group

Ctrl7-11M/043+053 Group

10Pn12-18M/043+053 Group

Ctrl12-18M/043+053 Group

Total subjects affected by non serious adverse events

subjects affected / exposed

0 / 9112 (0.00%)

0 / 4399 (0.00%)

0 / 8427 (0.00%)

0 / 4473 (0.00%)

0 / 3689 (0.00%)

0 / 1812 (0.00%)

0 / 6249 (0.00%)

0 / 3020 (0.00%)

0 / 10273 (0.00%)

0 / 10054 (0.00%)

0 / 10201 (0.00%)

0 / 3880 (0.00%)

0 / 1908 (0.00%)

0 / 6535 (0.00%)

0 / 3126 (0.00%)

More information

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Were there any global substantial amendments to the protocol? Yes

04 Feb 2009

Amendment 1 of the 10PN-PD-DIT-043 (111442) study protocol was developed for the following reasons: (1) Addition of collection of data on respiratory tract infections (RTIs), including acute otitis media (AOM) in a subset of subjects in Turku area; (2) Addition of 6 clusters located in some selected municipalities where no collaboration with health care centres had been set up but where there was opportunity for parent(s) to let their child participate in nested study 10PN-PD-DIT-053 (112595) and to receive the same vaccination as in the current study (i.e. Espoo, Vantaa and surroundings municipalities and municipalities surrounding Oulu); and (3) The National Public Health Institute (KTL) and the National Research and Development Centre for Welfare and Health (STAKES) were merged into the National Institute for Health and Welfare (THL).

22 Aug 2011

Amendment 2 was developed for the following reasons: (1) The study enrolment reached only 50% of the initial recruitment plan; therefore, there was a need to redefine the conditions for triggering IPD effectiveness analysis: (a) the study follow-up period for primary analysis on invasive disease (ID) cases was to end on 31 January 2012 (data lock point for ID cases), i.e. at least 30 months after study start. This would allow inclusion of an age-related IPD peak at 1119 months of age in the youngest enrolled subjects and an expected seasonal invasive pneumococcal disease (IPD) peak in the fall of 2011, thereby increasing the potential to accrue additional IPD cases; (b) Reaching a minimum number of 21 culture-confirmed vaccine-type IPD cases in the infant group was no longer a condition for triggering IPD effectiveness analysis because that minimum number was most probably not met due to the lower enrolment numbers. The estimated target number of vaccine-type IPD cases was adjusted accordingly, based on an assumed vaccine efficacy estimate and the currently available information on the total number of IPD cases by age cohort. Taking into account the lower than expected number of enrolled subjects, associated number of overall IPD cases reported so far and impact on power when considering 80% vaccine efficacy for the 2+1 vaccination schedule, it was decided to evaluate the effectiveness of the 10Pn-PD-DiT vaccine to prevent vaccine-type IPD in the infants assigned to a 2+1 vaccination course as a first secondary objective instead of the second primary objective (sequential) but to keep the pre-defined statistical criteria for success. (2) Following IDMC recommendation, it was decided to have the chest X-rays from the hospital-diagnosed pneumonia cases in the vaccinated population evaluated by an independent review panel according to World Health Organisation (WHO) guidelines for study purposes. The appropriate sections of the protocol were adjusted to reflect this

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 III/IV, cluster-randomized, controlled study to evaluate the effectiveness of GlaxoSmithKline Biologicals’ 10-valent pneumococcal and non-typeable Haemophilus influenzae protein D conjugate vaccine in reducing the incidence of invasive diseases.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PYAR as regards subjects with culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.

Primary: PYAR as regards subjects with culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: A phase III/IV, cluster-randomized, controlled study to evaluate the effectiveness of GlaxoSmithKline Biologicals’ 10-valent pneumococcal and non-typeable Haemophilus influenzae protein D conjugate vaccine in reducing the incidence of invasive diseases.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PYAR as regards subjects with culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.

Primary: PYAR as regards subjects with culture-confirmed IPD due to any of the 10 pneumococcal vaccine serotypes.

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A phase III/IV, cluster-randomized, controlled study to evaluate the effectiveness of GlaxoSmithKline Biologicals’ 10-valent pneumococcal and non-typeable Haemophilus influenzae protein D conjugate vaccine in reducing the incidence of invasive diseases.