Download PDF

Clinical Trial Results:
Prophylactic antipyretic treatment in children receiving booster dose of pneumococcal vaccine GSK1024850A and Infanrix hexa™ and assessment of impact of pneumococcal vaccination on nasopharyngeal carriage.

Summary
EudraCT number	2006-001481-17
Trial protocol	CZ
Global end of trial date	17 Feb 2009

Results information
Results version number	v2
This version publication date	07 Jul 2016
First version publication date	30 Jul 2015
Other versions	v1 , v3
Version creation reason	Correction of full data set 1 Group was defined as baseline group in subject disposition while this group is the pooling of 2 other groups already defined as baseline groups. As a consequence the number of subjects enrolled in the study was not correct.

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

107137

ISRCTN number

US NCT number

NCT00496015

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

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

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

24 Jul 2009

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Mar 2008

Global end of trial reached?

Yes

Global end of trial date

17 Feb 2009

Was the trial ended prematurely?

Main objective of the trial

To determine the percentage reduction in febrile reactions (rectal temperature >=38.0°C or oral/axillary/tympanic >=37.5°C) when prophylactic antipyretic treatment is administered compared to no prophylactic antipyretic treatment, after booster vaccination with GSK Biologicals’ 10-valent pneumococcal conjugate vaccine and routine DTPa-HBV-IPV/Hib (Infanrix hexa) vaccination in children at 12-15 months of age.

Protection of trial subjects

The vaccines were observed closely for at least 30 minutes, with appropriate medical treatment readily available in case of a rare anaphylactic reaction following the administration of vaccine(s).

Background therapy

Evidence for comparator

Actual start date of recruitment

02 Jul 2007

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Czech Republic: 750

Worldwide total number of subjects

750

EEA total number of subjects

750

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)

750

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

This was a multicenter study with the same centers as the primary vaccination study 10PN-PD-DIT-010 (107017) and all subjects enrolled in the primary vaccination study and having received 10Pn-PD-DIT vaccine were invited to participate in the study. In addition, an age-matched pneumococcal vaccine unprimed control group has been enrolled.

Screening details

During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

10Pn-PD-DiT/ Paracetamol Group

Arm description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa along with prophylactic antipyretic treatment. Before implementation of protocol amendment 3, as originally planned, subjects in this Group received paracetamol with the booster vaccines. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none. It was therefore decided to discontinue the administration of paracetamol during the booster phase during the enrollment of the present study and a second group was created after the protocol amendment (see 10PN-PD-DIT group definition).

Arm type

Experimental

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

GSK1024850A

Other name

10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the right thigh or deltoid region.

Investigational medicinal product name

Infanrix™ Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the left thigh or deltoid region.

Investigational medicinal product name

PANADOL 125 mg

Investigational medicinal product code

Other name

Panadol 125

Pharmaceutical forms

Suppository

Routes of administration

Rectal use

Dosage and administration details

The prophylactic antipyretic treatment was administered as rectal suppositories according to the subject’s body weight.

10Pn-PD-DiT Group

Arm description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. Before the implementation of protocol amendment 3: as originally planned, subjects should receive paracetamol with the booster vaccines. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none.It was therefore decided to discontinue the administration of paracetamol during the booster phase, e.g. during the enrollment in the present study for the subjects belonging to this group.

Arm type

Experimental

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

GSK1024850A

Other name

10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the right thigh or deltoid region.

Investigational medicinal product name

Infanrix™ Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the left thigh or deltoid region.

10Pn-Pre Group

Arm description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none. To avoid introducing a bias in the study results because of the split of 2 groups: 10PN-PD-DIT Paracetamol and 10PN-PD-DIT groups at that point in time, the control 10Pn Group was also divided into 2 subgroups:10Pn-Pre (subjects enrolled before protocol amendment 3) and 10Pn-Post (subjects enrolled after protocol amendment 3).

Arm type

Active comparator

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

GSK1024850A

Other name

10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the right thigh or deltoid region.

Investigational medicinal product name

Infanrix™ Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the left thigh or deltoid region.

10Pn-Post Group

Arm description

Arm type

Active comparator

Investigational medicinal product name

10-valent Streptococcus pneumoniae conjugate vaccine

Investigational medicinal product code

GSK1024850A

Other name

10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix™, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the right thigh or deltoid region.

Investigational medicinal product name

Infanrix™ Hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

one booster dose at 12-15 months of age, into the left thigh or deltoid region.

Unprimed Group

Arm description

Age-matched pneumococcal vaccine unprimed group receiving a single dose of meningococcal conjugate vaccine GSK134612 co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa).

Arm type

Active comparator

Investigational medicinal product name

Meningococcal vaccine GSK134612

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Single dose, intramuscularly injection in the right thigh at 12-15 months of age.

Investigational medicinal product name

Infanrix™ hexa

Investigational medicinal product code

Other name

DTPa-IPV-HBV/Hib, Infanrix Hexa GSK Biologicals’ diphtheria-tetanus-acellular pertussis

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Single dose, intramuscularly injection in the left thigh at 12-15 months of age.

Number of subjects in period 1	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Started	178	27	172	37	336
Completed	177	27	172	36	336
Not completed	1	0	0	1	0
Unspecified	1	-	-	1	-

Baseline characteristics

Top of page

Reporting group title

10Pn-PD-DiT/ Paracetamol Group

Reporting group description

Reporting group title

10Pn-PD-DiT Group

Reporting group description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. Before the implementation of protocol amendment 3: as originally planned, subjects should receive paracetamol with the booster vaccines. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none.It was therefore decided to discontinue the administration of paracetamol during the booster phase, e.g. during the enrollment in the present study for the subjects belonging to this group.

Reporting group title

10Pn-Pre Group

Reporting group description

Reporting group title

10Pn-Post Group

Reporting group description

Reporting group title

Unprimed Group

Reporting group description

Age-matched pneumococcal vaccine unprimed group receiving a single dose of meningococcal conjugate vaccine GSK134612 co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa).

Reporting group values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group	Total
Number of subjects	178	27	172	37	336	750
Age categorical
Units: Subjects
In utero						0
Preterm newborn infants (gestational age < 37 wks)						0
Newborns (0-27 days)						0
Infants and toddlers (28 days-23 months)						0
Children (2-11 years)						0
Adolescents (12-17 years)						0
Adults (18-64 years)						0
From 65-84 years						0
85 years and over						0
Age continuous
Units: months
arithmetic mean (standard deviation)	12.6 ( 0.77 )	13.2 ( 0.74 )	12.7 ( 0.77 )	13.1 ( 1.15 )	13.1 ( 1.1 )	-
Gender categorical
Units: Subjects
Female	90	11	79	18	155	353
Male	88	16	93	19	181	397

Subject analysis set title

Pooled primed Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

For carriage analyses the 10PN-PD-DIT/Paracetamol, 10PN-PD-DIT, 10Pn-PRE and 10Pn-POST groups were pooled (pooled primed groups).

Subject analysis set title

10Pn Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

pooled group with subjects from both 10Pn-Pre and 10Pn-Post groups

Subject analysis sets values	Pooled primed Group	10Pn Group
Number of subjects	414	209
Age categorical
Units: Subjects
In utero
Preterm newborn infants (gestational age < 37 wks)
Newborns (0-27 days)
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
85 years and over
Age continuous
Units: months
arithmetic mean (standard deviation)	12.73 ( 0.83 )	12.8 ( 0.86 )
Gender categorical
Units: Subjects
Female	198	97
Male	216	112

End points

Top of page

Reporting group title

10Pn-PD-DiT/ Paracetamol Group

Reporting group description

Reporting group title

10Pn-PD-DiT Group

Reporting group description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. Before the implementation of protocol amendment 3: as originally planned, subjects should receive paracetamol with the booster vaccines. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none.It was therefore decided to discontinue the administration of paracetamol during the booster phase, e.g. during the enrollment in the present study for the subjects belonging to this group.

Reporting group title

10Pn-Pre Group

Reporting group description

Reporting group title

10Pn-Post Group

Reporting group description

Reporting group title

Unprimed Group

Reporting group description

Age-matched pneumococcal vaccine unprimed group receiving a single dose of meningococcal conjugate vaccine GSK134612 co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa).

Subject analysis set title

Pooled primed Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

For carriage analyses the 10PN-PD-DIT/Paracetamol, 10PN-PD-DIT, 10Pn-PRE and 10Pn-POST groups were pooled (pooled primed groups).

Subject analysis set title

10Pn Group

Subject analysis set type

Sub-group analysis

Subject analysis set description

pooled group with subjects from both 10Pn-Pre and 10Pn-Post groups

Primary: Number of subjects reported with core fever (rectal temperature) ≥38.0 degrees Celsius (ºC).

Top of page

End point title

Number of subjects reported with core fever (rectal temperature) ≥38.0 degrees Celsius (ºC).

End point description

End point type

Primary

End point timeframe

Within 4 days (Day 0-3) after primary vaccine dose.

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	178	27	172	37	336
Units: Subjects
Fever >= 38.0°C	64	14	100	16	146

Difference between groups (core fever >=38.0°C)

Statistical analysis description

Analysis aimed at demonstrating the superiority in terms of post-immunization core fever >= 38.0°C of 10Pn-PD-DiT vaccine when co-administered with paracetamol compared to the 10Pn-PD-DiT vaccine when administered without such co-administration. Towards this analysis, standardized asymptotic 95% confidence interval (CI) for the groups difference [10Pn-pre Group minus 10Pn-PD-DiT/Paracetamol Group] in percentages of subjects reported with core fever >= 38.0°C was computed.

Comparison groups

10Pn-Pre Group v 10Pn-PD-DiT/ Paracetamol Group

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

Method

Parameter type

Difference in percentages

Point estimate

22.18

Confidence interval

level

95%

sides

2-sided

lower limit

11.78

upper limit

32.11

Notes
[1] - Superiority was demonstrated if the lower limit (LL) computed standardized asymptotic 95% CI was above 0%.

Secondary: Number of subjects reported with core fever (rectal temperature) > 39.0°C.

Top of page

End point title

Number of subjects reported with core fever (rectal temperature) > 39.0°C.

End point description

End point type

Secondary

End point timeframe

Within 4 days (Day 0-3) after primary vaccination dose.

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	178	27	172	37	336
Units: Subjects
Fever (rectal temperature) > 39.0°C	4	0	14	1	16

No statistical analyses for this end point

Secondary: Number of subjects reported with any and Grade 3 solicited local symptoms.

Top of page

End point title

Number of subjects reported with any and Grade 3 solicited local symptoms.

End point description

Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any occurrence of the specified symptom regardless of intensity. Grade 3 pain was defined as cried when limb was moved/spontaneously painful. Grade 3 redness/swelling was defined as redness/swelling > 30 millimeters from injection site.

End point type

Secondary

End point timeframe

Within 4 days after primary vaccination.

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	178	27	172	37	336
Units: Subjects
Any pain	54	10	79	19	114
Grade 3 pain	2	2	10	3	4
Any redness	89	9	74	12	146
Grade 3 redness	7	1	14	1	16
Any swelling	52	8	50	13	71
Grade 3 swelling	2	1	9	3	12

No statistical analyses for this end point

Secondary: Number of subjects reported with any and Grade 3 solicited general symptoms.

Top of page

End point title

Number of subjects reported with any and Grade 3 solicited general symptoms.

End point description

Solicited general symptoms assessed were drowsiness, fever (rectal temperature >= 38.5°C), irritability and loss of appetite. Any was defined as any occurrence of the specified symptom regardless of intensity and relation to vaccination. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Grade 3 fever was defined as rectal temperature >40.0°C. Grade 3 irritability was defined as crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite was defined as not eating at all.

End point type

Secondary

End point timeframe

Within 4 days after primary vaccination.

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	178	27	172	37	336
Units: Subjects
Any drowsiness	91	11	84	18	146
Grade 3 drowsiness	0	0	1	1	2
Any fever (rectal temperature >=38.0°C)	64	14	100	16	146
Grade 3 fever (rectal temperature > 40.0°C)	1	0	1	0	3
Any irritability	86	17	105	19	147
Grade 3 irritability	1	0	2	2	2
Any loss of appetite	47	8	46	10	88
Grade 3 loss of appetite	0	0	4	1	3

No statistical analyses for this end point

Secondary: Number of subjects reported with unsolicited adverse events (AEs).

Top of page

End point title

Number of subjects reported with unsolicited adverse events (AEs). ^[2]

End point description

End point type

Secondary

End point timeframe

Within 31 days (Day 0-30) after primary vaccine dose.

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on baseline groups except forthe 10Pn -Pre and 10Pn-Post Group, results were presented for the pooled 10Pn Group included subjects from 10Pn-Pre Group + 10Pn-Post group.

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	Unprimed Group	10Pn Group
Number of subjects analysed	178	27	336	209
Units: Subjects
Subject(s) with any AE(s)	22	3	64	30

No statistical analyses for this end point

Secondary: Number of subjects reported with serious adverse events (SAEs).

Top of page

End point title

Number of subjects reported with serious adverse events (SAEs).

End point description

End point type

Secondary

End point timeframe

Throughout the entire study period (Month 0-Month 12).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	178	27	172	37	336
Units: Subjects
Subject(s) with any SAE(s)	13	5	13	4	30

No statistical analyses for this end point

Secondary: Number of subjects reported with AEs resulting in rash, new onset of chronic illness (NOCI), emergency room (ER) visits and non-routine physician office visits.

Top of page

End point title

Number of subjects reported with AEs resulting in rash, new onset of chronic illness (NOCI), emergency room (ER) visits and non-routine physician office visits. ^[3]

End point description

End point type

Secondary

End point timeframe

Up to 6 months after vaccination with GSK Biologicals’ meningococcal serogroups A, C, W-135, Y tetanus toxid conjugate vaccine.

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated only on unprimed group, according to end point specification of the protocol.

End point values	Unprimed Group
Number of subjects analysed	336
Units: Subjects
Subject(s) with any rash(es)	7
Subject(s) with any NOCI(s)	1
Subject(s) with any ER visit(s)	0
Subject(s) with any visit(s) at physician office	53

No statistical analyses for this end point

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL.

Top of page

End point title

Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL.

End point description

Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA). Seroprotection and seropositivity cut-offs for the assay were >= 0.20 and 0.05 μg/mL, respectively.

End point type

Secondary

End point timeframe

Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	141	25	168	37	289
Units: Subjects
ANTI-1 PRE(N=132,25,163,37,284)	74	14	115	27	6
ANTI-1 M1(N=140,24,167,36,244)	140	24	167	36	5
ANTI-1 M12(N=138,25,167,36,263)	89	11	122	30	11
ANTI-4 PRE(N=139,25,160,35,289)	123	15	147	31	6
ANTI-4 M1(N=141,24,167,37,261)	141	24	167	37	6
ANTI-4 M12(N=139,25,168,36,288)	103	14	147	27	20
ANTI-5 PRE(N=131,25,156,37,277)	102	15	142	30	6
ANTI-5 M1(N=140,24,167,36,256)	140	23	167	36	10
ANTI-5 M12(N=139,25,168,36,281)	113	18	159	30	31
ANTI-6B PRE(N=139,25,164,37,282)	110	13	143	32	1
ANTI-6B M1(N=140,24,167,36,282)	134	21	166	35	1
ANTI-6B M12(N=139,25,168,36,289)	97	18	148	30	21
ANTI-7F PRE(N=136,24,159,35,281)	130	21	156	34	5
ANTI-7F M1(N=140,25,167,37,265)	140	25	167	37	9
ANTI-7F M12(N=139,25,168,36,283)	132	21	165	36	20
ANTI-9V PRE(N=127,24,154,35,279)	117	20	152	34	5
ANTI-9V M1(N=141,25,167,37,266)	141	24	167	37	10
ANTI-9V M12(N=139,25,168,36,285)	129	20	166	35	30
ANTI-14 PRE(N=136,25,164,37,274)	131	22	159	35	25
ANTI-14 M1(N=140,24,167,36,261)	140	24	166	36	29
ANTI-14 M12(N=139,25,168,36,277)	131	21	166	34	63
ANTI-18C PRE(N=135,25,163,35,275)	118	14	154	29	8
ANTI-18C M1(N=141,25,167,37,269)	141	25	167	37	9
ANTI-18C M12(N=139,25,168,36,281)	113	18	157	35	29
ANTI-19F PRE(N=137,25,165,37,278)	128	21	163	36	17
ANTI-19F M1(N=141,25,167,37,269)	138	25	165	37	24
ANTI-19F M12(N=138,25,168,36,283)	135	22	165	36	90
ANTI-23F PRE(N=136,25,155,35,275)	103	14	132	30	2
ANTI-23F M1(N=140,24,167,37,259)	135	21	163	36	4
ANTI-23F M12(N=139,25,168,36,289)	115	16	154	33	24

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F).

Top of page

End point title

Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F).

End point description

Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA). Seropositivity cut-off for the assay was >= 0.05 μg/mL.

End point type

Secondary

End point timeframe

Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	141	25	168	37	289
Units: μg/mL
geometric mean (confidence interval 95%)
ANTI-1 PRE(N=132,25,163,37,284)	0.22 (0.19 to 0.25)	0.18 (0.12 to 0.27)	0.31 (0.27 to 0.35)	0.26 (0.19 to 0.35)	0.03 (0.03 to 0.03)
ANTI-1 M1(N=140,24,167,36,244)	1.67 (1.47 to 1.9)	1.64 (1.08 to 2.47)	2.62 (2.3 to 2.99)	2.97 (2.21 to 3.99)	0.03 (0.03 to 0.03)
ANTI-1 M12(N=138,25,167,36,263)	0.26 (0.22 to 0.31)	0.18 (0.12 to 0.29)	0.39 (0.34 to 0.45)	0.41 (0.31 to 0.56)	0.04 (0.04 to 0.04)
ANTI-4 PRE(N=139,25,160,35,289)	0.4 (0.35 to 0.45)	0.24 (0.17 to 0.35)	0.6 (0.52 to 0.69)	0.45 (0.35 to 0.58)	0.03 (0.03 to 0.03)
ANTI-4 M1(N=141,24,167,37,261)	3.01 (2.69 to 3.36)	2.84 (1.98 to 4.08)	4.21 (3.72 to 4.76)	3.95 (2.97 to 5.26)	0.03 (0.03 to 0.03)
ANTI-4 M12(N=139,25,168,36,288)	0.34 (0.29 to 0.39)	0.21 (0.13 to 0.33)	0.5 (0.43 to 0.56)	0.55 (0.39 to 0.78)	0.04 (0.03 to 0.04)
ANTI-5 PRE(N=131,25,156,37,277)	0.36 (0.32 to 0.42)	0.31 (0.18 to 0.52)	0.59 (0.52 to 0.68)	0.53 (0.36 to 0.78)	0.04 (0.03 to 0.04)
ANTI-5 M1(N=140,24,167,36,256)	2.3 (2.04 to 2.6)	2 (1.31 to 3.06)	3.68 (3.26 to 4.15)	3.03 (2.16 to 4.26)	0.04 (0.03 to 0.04)
ANTI-5 M12(N=139,25,168,36,281)	0.42 (0.36 to 0.48)	0.35 (0.23 to 0.52)	0.72 (0.63 to 0.83)	0.58 (0.42 to 0.81)	0.06 (0.05 to 0.06)
ANTI-6B PRE(N=139,25,164,37,282)	0.35 (0.3 to 0.41)	0.18 (0.1 to 0.32)	0.55 (0.48 to 0.63)	0.5 (0.35 to 0.72)	0.03 (0.03 to 0.03)
ANTI-6B M1(N=140,24,167,36,282)	1.35 (1.12 to 1.61)	0.89 (0.46 to 1.72)	2.45 (2.17 to 2.77)	2.25 (1.51 to 3.33)	0.03 (0.03 to 0.03)
ANTI-6B M12(N=139,25,168,36,289)	0.4 (0.32 to 0.5)	0.36 (0.19 to 0.66)	0.56 (0.47 to 0.68)	0.54 (0.37 to 0.81)	0.04 (0.04 to 0.04)
ANTI-7F PRE(N=136,24,159,35,281)	0.74 (0.65 to 0.84)	0.55 (0.4 to 0.76)	1.05 (0.93 to 1.18)	0.87 (0.66 to 1.13)	0.03 (0.03 to 0.03)
ANTI-7F M1(N=140,25,167,37,265)	2.9 (2.59 to 3.25)	2.37 (1.86 to 3.03)	4.13 (3.69 to 4.63)	4.38 (3.35 to 5.72)	0.03 (0.03 to 0.03)
ANTI-7F M12(N=139,25,168,36,283)	0.68 (0.6 to 0.78)	0.45 (0.32 to 0.63)	0.91 (0.82 to 1.02)	0.96 (0.74 to 1.24)	0.04 (0.04 to 0.04)
ANTI-9V PRE(N=127,24,154,35,279)	0.61 (0.53 to 0.7)	0.59 (0.33 to 1.05)	1 (0.88 to 1.13)	0.99 (0.78 to 1.26)	0.03 (0.03 to 0.03)
ANTI-9V M1(N=141,25,167,37,266)	2.86 (2.52 to 3.23)	2.57 (1.73 to 3.81)	4.39 (3.91 to 4.94)	4.35 (3.3 to 5.73)	0.03 (0.03 to 0.03)
ANTI-9V M12(N=139,25,168,36,285)	0.67 (0.56 to 0.8)	0.55 (0.33 to 0.92)	0.97 (0.85 to 1.12)	0.86 (0.64 to 1.17)	0.04 (0.04 to 0.05)
ANTI-14 PRE(N=136,25,164,37,274)	0.82 (0.69 to 0.96)	0.52 (0.36 to 0.74)	1.57 (1.32 to 1.86)	1.27 (0.86 to 1.88)	0.04 (0.04 to 0.05)
ANTI-14 M1(N=140,24,167,36,261)	4.58 (4.05 to 5.18)	4.37 (3.01 to 6.33)	5.95 (5.28 to 6.71)	5.86 (4.35 to 7.89)	0.05 (0.04 to 0.05)
ANTI-14 M12(N=139,25,168,36,277)	0.89 (0.73 to 1.09)	0.94 (0.48 to 1.84)	1.54 (1.3 to 1.81)	1.25 (0.9 to 1.76)	0.11 (0.09 to 0.13)
ANTI-18C PRE(N=135,25,163,35,275)	0.47 (0.41 to 0.54)	0.29 (0.2 to 0.43)	0.78 (0.69 to 0.89)	0.54 (0.39 to 0.76)	0.03 (0.03 to 0.03)
ANTI-18C M1(N=141,25,167,37,269)	4.96 (4.4 to 5.6)	3.46 (2.35 to 5.09)	7 (6.28 to 7.79)	6.13 (4.85 to 7.75)	0.03 (0.03 to 0.03)
ANTI-18C M12(N=139,25,168,36,281)	0.56 (0.47 to 0.66)	0.44 (0.27 to 0.72)	1.05 (0.92 to 1.21)	0.92 (0.69 to 1.21)	0.04 (0.04 to 0.05)
ANTI-19F PRE(N=137,25,165,37,278)	0.98 (0.81 to 1.19)	0.63 (0.39 to 1.02)	1.48 (1.27 to 1.73)	1.4 (1 to 1.97)	0.03 (0.03 to 0.04)
ANTI-19F M1(N=141,25,167,37,269)	6 (5.08 to 7.08)	4.84 (3.47 to 6.77)	7.55 (6.48 to 8.79)	8.77 (6.68 to 11.53)	0.05 (0.04 to 0.05)
ANTI-19F M12(N=138,25,168,36,283)	1.46 (1.18 to 1.82)	0.82 (0.56 to 1.2)	1.8 (1.52 to 2.13)	2.04 (1.41 to 2.94)	0.12 (0.1 to 0.14)
ANTI-23F PRE(N=136,25,155,35,275)	0.38 (0.31 to 0.46)	0.3 (0.16 to 0.58)	0.54 (0.45 to 0.64)	0.45 (0.31 to 0.65)	0.03 (0.03 to 0.03)
ANTI-23F M1(N=140,24,167,37,259)	1.99 (1.67 to 2.38)	1.33 (0.64 to 2.78)	2.92 (2.5 to 3.4)	3.86 (2.52 to 5.91)	0.03 (0.03 to 0.03)
ANTI-23F M12(N=139,25,168,36,289)	0.46 (0.38 to 0.56)	0.29 (0.16 to 0.52)	0.8 (0.67 to 0.95)	0.98 (0.69 to 1.39)	0.04 (0.03 to 0.04)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

End point description

OPA titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.

End point type

Secondary

End point timeframe

Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	131	25	161	35	135
Units: Titers
geometric mean (confidence interval 95%)
OPSONO-1 PRE(N=125,25,152,31,26)	6.1 (5 to 7.4)	5.6 (4 to 8)	8.1 (6.6 to 10)	6 (4.2 to 8.5)	4.9 (3.7 to 6.5)
OPSONO-1 M1(N=130,23,156,34,39)	144.6 (109.6 to 190.6)	193.4 (95.8 to 390.8)	417 (330.6 to 526.2)	325 (178.8 to 590.7)	5.1 (4.1 to 6.4)
OPSONO-1 M12(N=129,21,153,34,126)	12.8 (10 to 16.5)	12.5 (6.8 to 23.2)	23.1 (18.2 to 29.2)	20.5 (13.1 to 32.3)	4.7 (4.3 to 5.1)
OPSONO-4 PRE(N=121,22,148,31,31)	23.8 (16.5 to 34.2)	8.8 (5.2 to 14.9)	44.9 (33.2 to 60.8)	29.7 (14.3 to 61.6)	5.9 (3.4 to 10.2)
OPSONO-4 M1(N=130,22,158,32,23)	1547.9 (1357.9 to 1764.4)	971.6 (615.8 to 1532.7)	2297 (2005.8 to 2630.4)	1303.2 (918.6 to 1849)	7.8 (3.6 to 16.8)
OPSONO-4 M12(N=125,21,152,33,119)	19.9 (13.9 to 28.6)	14.9 (6.4 to 34.8)	51.2 (36.2 to 72.4)	72.5 (33.7 to 156.1)	6.8 (5 to 9.3)
OPSONO-5 PRE(N=121,24,146,31,26)	8.5 (7 to 10.4)	10.4 (6.2 to 17.4)	16.6 (13.2 to 20.9)	15.1 (8.8 to 25.9)	4.2 (3.8 to 4.7)
OPSONO-5 M1(N=130,23,156,34,45)	134.3 (109.8 to 164.2)	105 (55.9 to 196.9)	289.3 (243.5 to 343.7)	227.7 (130.7 to 396.6)	4.3 (3.8 to 4.8)
OPSONO-5 M12(N=124,21,154,32,135)	10.3 (8.3 to 12.9)	10.5 (5.9 to 18.7)	23.7 (18.9 to 29.8)	15.4 (10.2 to 23.2)	4 (4 to 4)
OPSONO-6B PRE(N=126,22,154,31,25)	32.5 (21.6 to 48.9)	15.9 (6 to 42.1)	45.2 (32.9 to 62.2)	49.7 (23 to 107.3)	9.9 (3.5 to 27.7)
OPSONO-6B M1(N=130,22,157,34,29)	496.7 (351.4 to 702.2)	148.3 (46.5 to 472.5)	985.7 (807.1 to 1203.9)	718.3 (445.7 to 1157.5)	20.9 (6.6 to 65.9)
OPSONO-6B M12(N=123,22,145,31,113)	46.9 (29.6 to 74.2)	97.7 (27.7 to 345.1)	53.9 (36.1 to 80.4)	29.4 (13.2 to 65.2)	19.1 (12 to 30.5)
OPSONO-7F PRE(N=115,22,148,32,23)	413.6 (266.1 to 642.9)	221.4 (65.7 to 745.9)	584.7 (426.1 to 802.3)	258.4 (119.9 to 556.7)	90 (23.2 to 349.8)
OPSONO-7F M1(N=130,23,158,34,28)	4025.8 (3457.3 to 4687.9)	1749 (1144.2 to 2673.4)	4674.7 (4102.2 to 5327)	2212.2 (1569.1 to 3118.7)	267.3 (89.1 to 801.2)
OPSONO-7F M12(N=130,25,159,34,118)	1503.3 (1209.1 to 1869.2)	1606.4 (1101.4 to 2343)	1285.7 (1050.8 to 1573)	1738.3 (1330.6 to 2271)	681.1 (499.7 to 928.3)
OPSONO-9V PRE(N=119,21,147,31,23)	420.7 (342.7 to 516.5)	472.9 (255.6 to 874.7)	407.7 (340.3 to 488.4)	365.7 (240.6 to 555.8)	69.2 (22.9 to 208.9)
OPSONO-9V M1(N=129,23,157,34,31)	2234.8 (1905.7 to 2620.7)	752.9 (476.9 to 1188.8)	2403.7 (2092.3 to 2761.4)	1155.5 (733.4 to 1820.4)	87.4 (45.2 to 169)
OPSONO-9V M12(N=131,25,161,35,124)	791.6 (647.4 to 967.9)	552.2 (337.1 to 904.6)	906.7 (757.6 to 1085.2)	716.8 (481 to 1068.2)	127.2 (86.8 to 186.2)
OPSONO-14 PRE(N=118,21,152,29,12)	189.7 (141.7 to 254)	150.2 (81.5 to 276.8)	293.2 (235.3 to 365.5)	227.4 (115.1 to 449.4)	11.5 (3.3 to 40.1)
OPSONO-14 M1(N=130,22,154,34,19)	1581.7 (1381.1 to 1811.4)	1515 (911.2 to 2519)	1865.2 (1633.4 to 2129.9)	1964.5 (1359.9 to 2837.9)	158 (59.4 to 420.2)
OPSONO-14 M12(N=117,15,147,32,98)	434.5 (353 to 534.8)	438.4 (137.7 to 1396)	447.5 (376 to 532.6)	558 (425 to 732.5)	287.8 (203.2 to 407.6)
OPSONO-18C PRE(N=124,23,148,24,38)	6.1 (5.2 to 7.2)	6 (3.7 to 9.7)	11.7 (9.2 to 15.1)	9.5 (4.9 to 18.5)	4.5 (3.5 to 5.8)
OPSONO-18C M1(N=128,22,154,34,42)	652.9 (553.5 to 770.1)	269.7 (128.9 to 564.3)	737.8 (633.6 to 859.1)	537.6 (370.9 to 779.3)	4 (4 to 4)
OPSONO-18C M12(N=121,23,154,28,124)	11.9 (8.9 to 16.1)	24.7 (9 to 67.5)	27.7 (21.3 to 36)	23.5 (11 to 50.3)	4.6 (4 to 5.3)
OPSONO-19F PRE(N=121,24,149,32,39)	21.2 (16.1 to 28)	17.4 (10.5 to 28.7)	35.1 (28 to 44)	36.4 (22 to 60.3)	5.3 (3.7 to 7.7)
OPSONO-19F M1(N=130,23,156,34,42)	629.4 (496.6 to 797.7)	372.9 (180.1 to 772.5)	1062.2 (871.8 to 1294.3)	1198.8 (807.1 to 1780.5)	4.5 (3.7 to 5.6)
OPSONO-19F M12(N=130,25,155,35,132)	64.3 (47.6 to 86.7)	39.4 (17.3 to 89.5)	101.3 (80.7 to 127)	121.3 (67.5 to 218.1)	6.4 (5.1 to 8.1)
OPSONO-23F PRE(N=122,20,149,31,25)	288.7 (192.1 to 434)	310.1 (85.9 to 1119.4)	408 (288.6 to 576.6)	305.3 (135 to 690.5)	20.2 (7.2 to 56.2)
OPSONO-23F M1(N=130,23,157,34,28)	2335.7 (2016.2 to 2705.7)	1223.1 (910.6 to 1642.8)	3154 (2658 to 3742.4)	1808.7 (1381.1 to 2368.7)	261.8 (97.9 to 700.5)
OPSONO-23F M12(N=122,20,152,33,124)	386.4 (250 to 597.2)	433.8 (110.1 to 1709.8)	857.5 (634 to 1159.7)	670.2 (331.9 to 1353.3)	147.1 (86.7 to 249.9)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against protein D (Anti-PD).

Top of page

End point title

Concentrations of antibodies against protein D (Anti-PD).

End point description

The seropositivity cut-off for the assay was ≥ 100 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per milliliter.

End point type

Secondary

End point timeframe

Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	140	25	167	37	270
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD-PRE (N=135,25,158,37,260)	365.1 (302.1 to 441.1)	356.5 (247 to 514.4)	685.5 (585.4 to 802.9)	584.3 (393.1 to 868.4)	65.6 (60.9 to 70.8)
Anti-PD-M1 (N=140,24,166,36,258)	1654 (1399.9 to 1954.4)	1813.5 (1111.5 to 2958.9)	3134.2 (2765.4 to 3552.1)	2612.3 (1804.4 to 3782.1)	64.6 (59.9 to 69.5)
Anti-PD-M12 (N=138,25,167,36,270)	468.1 (381.8 to 573.8)	418 (259.9 to 672.3)	834.6 (720 to 967.5)	713.4 (476.9 to 1067.4)	74.4 (67.8 to 81.6)

No statistical analyses for this end point

Secondary: Antibody concentrations against pneumococcal serotypes 6A and 19A (anti-6A and 19A).

Top of page

End point title

Antibody concentrations against pneumococcal serotypes 6A and 19A (anti-6A and 19A).

End point description

Anti-6A and 19A antibody concentrations were measured by 22F-inhibition Enzyme-Linked ImmunoSorbent Assay (ELISA).

End point type

Secondary

End point timeframe

Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	139	25	168	37	288
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A-PRE N(=136,25,161,37,278)	0.12 (0.1 to 0.15)	0.08 (0.05 to 0.12)	0.21 (0.18 to 0.26)	0.19 (0.12 to 0.29)	0.03 (0.03 to 0.03)
Anti-6A-M1 (N=138,25,166,36,288)	0.4 (0.31 to 0.51)	0.29 (0.15 to 0.55)	0.86 (0.69 to 1.07)	0.75 (0.43 to 1.3)	0.03 (0.03 to 0.03)
Anti-6A-M12 (N=139,25,167,36,279)	0.14 (0.11 to 0.18)	0.1 (0.07 to 0.16)	0.24 (0.2 to 0.3)	0.2 (0.13 to 0.29)	0.04 (0.03 to 0.04)
Anti-19A-PRE (n=138,25,165,36,277)	0.15 (0.13 to 0.18)	0.12 (0.07 to 0.19)	0.23 (0.19 to 0.27)	0.2 (0.14 to 0.29)	0.03 (0.03 to 0.04)
Anti-19A-M1 (N=138,25,166,37,276)	0.84 (0.67 to 1.05)	0.56 (0.29 to 1.09)	1.34 (1.09 to 1.66)	1.54 (0.98 to 2.43)	0.04 (0.03 to 0.04)
Anti-19A-M12 (N=139,25,168,36,284)	0.22 (0.17 to 0.28)	0.13 (0.08 to 0.22)	0.36 (0.3 to 0.44)	0.41 (0.26 to 0.65)	0.06 (0.05 to 0.07)

No statistical analyses for this end point

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A.

Top of page

End point title

Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A.

End point description

OPA titers against pneumococcal serotypes 6A and 19A (Opsono-6A and 19A) were calculated, expressed as geometric mean titers (GMTs) and tabulated. The seropositivity cut-off for the assay was ≥ 8.

End point type

Secondary

End point timeframe

Prior to booster vaccination (PRE), 1 month (M1) and 12 months (M12) post-booster vaccination)

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	129	22	153	33	131
Units: Titers
geometric mean (confidence interval 95%)
OPSONO-6A-PRE (N=116,19,139,20,24)	72.4 (48.3 to 108.4)	35.6 (12.2 to 104.1)	65.4 (45.7 to 93.7)	66 (25.7 to 169.5)	9.7 (4.7 to 20)
OPSONO-6A-M1 (N=124,21,149,31,16)	251.5 (180.2 to 351)	105.1 (40.6 to 271.8)	401.7 (319.5 to 505.2)	403.7 (253.5 to 642.9)	16.1 (5 to 52)
OPSONO-6A-M12 (N=111,17,131,29,115)	59.4 (38.8 to 91)	23 (8.4 to 62.6)	52.1 (35.6 to 76.3)	37.2 (17.5 to 79)	17.1 (11.7 to 24.9)
OPSONO-19A-PRE (N=118,21,141,28,36)	5 (4.3 to 5.7)	4.9 (3.2 to 7.3)	4.8 (4.3 to 5.4)	5 (3.6 to 6.9)	4 (4 to 4)
OPSONO-19A-M1 (N=129,18,151,31,45)	39.2 (26.4 to 58.2)	39.7 (11.5 to 137.4)	89.7 (61.2 to 131.6)	99.6 (40.8 to 243.1)	4 (4 to 4)
OPSONO-19A-M12 (N=127,22,153,33,131)	7 (5.5 to 8.8)	4.8 (3.6 to 6.5)	8.9 (7.1 to 11.1)	9.5 (5.6 to 16.1)	4.7 (4.2 to 5.2)

No statistical analyses for this end point

Secondary: Number of subjects with titers ≥ 1:8 and 1:128 for meningococcal polysaccharides A , C, W-135 and Y serum bactericidal antibodies, using baby rabbit complement for assay (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) in the unprimed Group.

Top of page

End point title

Number of subjects with titers ≥ 1:8 and 1:128 for meningococcal polysaccharides A , C, W-135 and Y serum bactericidal antibodies, using baby rabbit complement for assay (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) in the unprimed Group. ^[4]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination.

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were only tabulated for subjects who received a vaccine including the respective antigens.

End point values	Unprimed Group
Number of subjects analysed	301
Units: Subjects
rSBA-MenA,Pre, ≥ 1:8 [N=244]	69
rSBA-MenA, Pre, ≥ 1:128 [N=244]	44
rSBA-MenA, M1, ≥ 1:8 [N=299]	298
rSBA-MenA, M1, ≥ 1:128 [N=299]	298
rSBA-MenA, M12, ≥ 1:8 [N=136]	136
rSBA-MenA, M12, ≥ 1:128 [N=136]	134
rSBA-MenC,Pre, ≥ 1:8 [N=295]	50
rSBA-MenC, Pre, ≥ 1:128 [N=295]	17
rSBA-MenC, M1, ≥ 1:8 [N=301]	300
rSBA-MenC, M1, ≥ 1:128 [N=301]	294
rSBA-MenC, M12, ≥ 1:8 [N=161]	154
rSBA-MenC, M12, ≥ 1:128 [N=161]	105
rSBA-MenW-135,Pre, ≥ 1:8 [N=287]	114
rSBA-MenW-135, Pre, ≥ 1:128 [N=287]	59
rSBA-MenW-135, M1, ≥ 1:8 [N=301]	301
rSBA-MenW-135, M1, ≥ 1:128 [N=301]	301
rSBA-MenW-135, M12, ≥ 1:8 [N=139]	138
rSBA-MenW-135, M12, ≥ 1:128 [N=139]	129
rSBA-MenY,Pre, ≥ 1:8 [N=297]	167
rSBA-MenY, Pre, ≥ 1:128 [N=297]	93
rSBA-MenY, M1, ≥ 1:8 [N=301]	300
rSBA-MenY, M1, ≥ 1:128 [N=301]	300
rSBA-MenY, M12, ≥ 1:8 [N=138]	137
rSBA-MenY, M12, ≥ 1:128 [N=138]	127

No statistical analyses for this end point

Secondary: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers in the unprimed Group.

Top of page

End point title

rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers in the unprimed Group. ^[5]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were only tabulated for subjects who received a vaccine including the respective antigens.

End point values	Unprimed Group
Number of subjects analysed	301
Units: Titers
geometric mean (confidence interval 95%)
rSBA-MenA,Pre [N=244]	11.5 (9.2 to 14.3)
rSBA-MenA, M1 [N=299]	2151.3 (1927.4 to 2401.2)
rSBA-MenA, M12 [N=136]	677.6 (579.9 to 791.8)
rSBA-MenC,Pre [N=295]	6.9 (6 to 8)
rSBA-MenC, M1 [N=301]	811.2 (728 to 904)
rSBA-MenC, M12 [N=161]	191.1 (153.5 to 238)
rSBA-MenW-135,Pre [N=287]	16.3 (13.2 to 20.1)
rSBA-MenW-135, M1 [N=301]	5393.6 (4888.2 to 5951.1)
rSBA-MenW-135, M12 [N=139]	573.1 (479.3 to 685.3)
rSBA-MenY,Pre [N=297]	30.2 (24.2 to 37.7)
rSBA-MenY, M1 [N=301]	2863.7 (2537.8 to 3231.4)
rSBA-MenY, M12 [N=138]	665.2 (547.9 to 807.7)

No statistical analyses for this end point

Secondary: Number of subjects with anti-polysaccharide N. meningitidis serogroup A (anti-PSA), C (anti-PSC), W (anti-PSW-135) and Y (anti-PSY) ≥ 0.3 μg/mL and 2.0 μg/mL in the unprimed Group.

Top of page

End point title

Number of subjects with anti-polysaccharide N. meningitidis serogroup A (anti-PSA), C (anti-PSC), W (anti-PSW-135) and Y (anti-PSY) ≥ 0.3 μg/mL and 2.0 μg/mL in the unprimed Group. ^[6]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post-vaccination.

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were only tabulated for subjects who received a vaccine including the respective antigens.

End point values	Unprimed Group
Number of subjects analysed	278
Units: Subjects
ANTI-PSA PRE(N=246)≥0.3 µg/mL	12
ANTI-PSA PRE(N=246)≥2.0 µg/mL	1
ANTI-PSA M1(N=272)≥0.3 µg/mL	271
ANTI-PSA M1(N=272)≥2.0 µg/mL	271
ANTI-PSA M12(N=153)≥0.3 µg/mL	133
ANTI-PSA M12(N=153)≥2.0 µg/mL	47
ANTI-PSC PRE(N=269)≥0.3 µg/mL	3
ANTI-PSC PRE(N=269)≥2.0 µg/mL	0
ANTI-PSC M1(N=278)≥0.3 µg/mL	278
ANTI-PSC M1(N=278)≥2.0 µg/mL	277
ANTI-PSC M12(N=157)≥0.3 µg/mL	94
ANTI-PSC M12(N=157)≥2.0 µg/mL	9
ANTI-PSW-135 PRE(N=236)≥0.3 µg/mL	1
ANTI-PSW-135 PRE(N=236)≥2.0 µg/mL	0
ANTI-PSW-135 M1(N=259)≥0.3 µg/mL	258
ANTI-PSW-135 M1(N=259)≥2.0 µg/mL	234
ANTI-PSW-135 M12(N=132)≥0.3 µg/mL	117
ANTI-PSW-135 M12(N=132)≥2.0 µg/mL	45
ANTI-PSY PRE(N=261)≥0.3 µg/mL	3
ANTI-PSY PRE(N=261)≥2.0 µg/mL	0
ANTI-PSY M1(N=263)≥0.3 µg/mL	261
ANTI-PSY M1(N=263)≥2.0 µg/mL	249
ANTI-PSY M12(N=135)≥0.3 µg/mL	131
ANTI-PSY M12(N=135)≥2.0 µg/mL	59

No statistical analyses for this end point

Secondary: Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibody concentrations in the unprimed Group.

Top of page

End point title

Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibody concentrations in the unprimed Group. ^[7]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(PRE), 1 month (M1) and 12 months (M12) post- vaccination.

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were only tabulated for subjects who received a vaccine including the respective antigens.

End point values	Unprimed Group
Number of subjects analysed	278
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PSA, Pre [N=246]	0.16 (0.15 to 0.17)
Anti-PSA, M1 [N=272]	36.28 (32.8 to 40.15)
Anti-PSA, M12 [N=153]	0.99 (0.82 to 1.19)
Anti-PSC, Pre [N=269]	0.15 (0.15 to 0.16)
Anti-PSC, M1 [N=278]	14.12 (13 to 15.32)
Anti-PSC, M12 [N=157]	0.42 (0.36 to 0.49)
Anti-PSW-135, Pre [N=236]	0.15 (0.15 to 0.15)
Anti-PSW-135, M1 [N=259]	6.11 (5.45 to 6.86)
Anti-PSW-135, M12 [N=132]	1.21 (0.98 to 1.48)
Anti-PSY, Pre [N=261]	0.15 (0.15 to 0.16)
Anti-PSY, M1 [N=263]	8.03 (7.17 to 8.99)
Anti-PSY, M12 [N=135]	1.81 (1.5 to 2.19)

No statistical analyses for this end point

Secondary: Anti-tetanus toxoids (anti-T) antibody concentrations in the unprimed Group.

Top of page

End point title

Anti-tetanus toxoids (anti-T) antibody concentrations in the unprimed Group. ^[8]

End point description

The seroprotection cut-off for the assay was ≥ 0.1 IU/mL.

End point type

Secondary

End point timeframe

Prior to vaccination (Pre).

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were only tabulated for subjects who received a vaccine including the respective antigens.

End point values	Unprimed Group
Number of subjects analysed	266
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-T, Pre [266]	0.512 (0.456 to 0.575)

No statistical analyses for this end point

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in the unprimed Group.

Top of page

End point title

Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in the unprimed Group. ^[9]

End point description

The seroprotection cut-off for the assay was ≥ 10 mIU/mL.

End point type

Secondary

End point timeframe

Prior to vaccination (Pre).

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were only tabulated for subjects who received a vaccine including the respective antigens.

End point values	Unprimed Group
Number of subjects analysed	2
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs, Pre [2]	1336.1 (52.3 to 34160.2)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T).

Top of page

End point title

Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T).

End point description

The seroprotection cut-off for the assay was ≥ 0.1 IU/mL.

End point type

Secondary

End point timeframe

1 month post-vaccination (M1).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	140	24	167	37	245
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-D, M1 (N=140,24,166,37,245)	10.112 (9.042 to 11.309)	9.839 (7.475 to 12.95)	12.285 (11.18 to 13.5)	11 (8.786 to 13.77)	7.291 (6.592 to 8.064)
Anti-T, M1 (N=139,24,167,37,245)	7.382 (6.639 to 8.208)	8.684 (6.37 to 11.839)	9.583 (8.927 to 10.287)	8.196 (6.829 to 9.837)	11.79 (10.684 to 13.011)

No statistical analyses for this end point

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations.

Top of page

End point title

Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations.

End point description

The seropositivity cut-off for the assay was ≥ 5 Enzyme-Linked ImmunoSorbent Assay (ELISA) units per millimiter (EL.U/mL).

End point type

Secondary

End point timeframe

1 month post-vaccination (M1).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	140	24	167	37	251
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PT, M1 (N=138,24,166,36,248)	83.3 (73.8 to 94)	81.6 (62.2 to 106.9)	82 (73.4 to 91.7)	76.7 (62.2 to 94.4)	163.1 (143 to 185.9)
Anti-FHA, M1 (N=140,24,167,37,251)	467.9 (422.4 to 518.3)	431.1 (318.8 to 582.9)	453.8 (412.6 to 499.1)	400.4 (321.8 to 498.2)	580.8 (532.2 to 633.8)
Anti-PRN, M1 (N=140,24,167,36,246)	222.8 (193.9 to 256)	153.4 (97.5 to 241.2)	254.9 (225.8 to 287.8)	220.4 (168.7 to 288)	350.7 (316.8 to 388.3)

No statistical analyses for this end point

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations (Month1).

Top of page

End point title

Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations (Month1).

End point description

The seroprotection cut-off for the assay was ≥ 10 mIU/mL. Dummy LL (0.0) and UL (99999.9) are entered when number of subjects analysed = 1.

End point type

Secondary

End point timeframe

1 month post-vaccination (M1).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	105	16	130	26	1
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs, M1	1883.9 (1332.9 to 2662.7)	1460.6 (816.4 to 2613.2)	2133 (1615 to 2817.1)	1818.5 (1142.8 to 2893.6)	20610 (0 to 99999.9)

No statistical analyses for this end point

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations.

Top of page

End point title

Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations.

End point description

The seroprotection cut-off for the assay was ≥ 0.15 µg/mL.

End point type

Secondary

End point timeframe

1 month post-vaccination (M1).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	141	24	167	36	269
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-PRP, M1	23.066 (18.806 to 28.291)	26.006 (15.56 to 43.463)	27.373 (22.915 to 32.697)	22.011 (16.288 to 29.745)	20.985 (17.966 to 24.511)

No statistical analyses for this end point

Secondary: Anti-Polio types 1, 2 and 3 titers (Month 1).

Top of page

End point title

Anti-Polio types 1, 2 and 3 titers (Month 1).

End point description

The seroprotection cut-off for the assay was ≥ 8. Dummy LL (0.0) and UL (99999.9) are entered when number of subjects analysed = 1.

End point type

Secondary

End point timeframe

1 month post-vaccination (M1).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	93	12	114	23	1
Units: Titers
geometric mean (confidence interval 95%)
Anti-Polio 1, M1 (N=93,12,114,23,1)	1193 (993.8 to 1432.2)	1534.2 (952 to 2472.5)	1058.7 (870.2 to 1288)	1208.6 (764.2 to 1911.2)	4096 (0 to 99999.9)
Anti-Polio 2, M1 (N=93,12,113,22,1)	1354.1 (1115.8 to 1643.3)	2047.9 (1246 to 3365.9)	1413.2 (1174.3 to 1700.7)	2215.8 (1544.4 to 3178.9)	8192 (0 to 99999.9)
Anti-Polio 3, M1 (N=92,12,114,23,1)	2354.2 (1946.1 to 2847.9)	2233.3 (1300.9 to 3834)	2647.5 (2221.5 to 3155.3)	3576.5 (2617.3 to 4887.2)	8192 (0 to 99999.9)

No statistical analyses for this end point

Secondary: Anti-HBs antibody concentrations (Month 12).

Top of page

End point title

Anti-HBs antibody concentrations (Month 12).

End point description

The seroprotection cut-off for the assay was ≥ 10 mIU/mL.

End point type

Secondary

End point timeframe

12 month post-vaccination (M12).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	107	16	133	20	19
Units: mIU/mL
geometric mean (confidence interval 95%)
Anti-HBs, M12	219.3 (164.8 to 291.7)	147.3 (62.6 to 346.9)	231.2 (179.7 to 297.6)	139.2 (74.3 to 260.9)	535.1 (277.8 to 1030.6)

No statistical analyses for this end point

Secondary: Anti-Polio type 1, 2 and 3 titers (Month 12).

Top of page

End point title

Anti-Polio type 1, 2 and 3 titers (Month 12).

End point description

The seroprotection cut-off for the assay was ≥ 8.

End point type

Secondary

End point timeframe

12 month post-vaccination (M12).

End point values	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	Unprimed Group
Number of subjects analysed	97	13	122	14	9
Units: Titers
geometric mean (confidence interval 95%)
Anti-Polio 1, M12 (N=97,13,122,14,9)	208.2 (164.7 to 263.2)	150.4 (87.2 to 259.3)	234.5 (189.5 to 290.3)	220.8 (92.3 to 528.2)	335.4 (146.4 to 768.2)
Anti-Polio 2, M12 (N=96,13,122,14,9)	311.2 (241.5 to 401)	212.4 (100.5 to 449)	310.6 (256 to 376.9)	400 (218.6 to 732.1)	322.7 (172.9 to 602.3)
Anti-Polio 3, M12 (N=97,13,122,14,9)	431.3 (332.4 to 559.5)	301 (125.8 to 720.4)	506.3 (406.3 to 630.7)	672.2 (330 to 1369.4)	203.3 (63.7 to 649.2)

No statistical analyses for this end point

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (vaccine serotypes).

Top of page

End point title

Number of nasopharyngeal swabs with S.pneumoniae (vaccine serotypes). ^[10]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Swabs
Pre (N=330,407)	53	43
M1 (N=332,408)	47	45
M3 (N=332,408)	55	49
M7 (N=334,406)	50	42
M12 (N=334,409)	43	34
Overall (N=336,414)	115	111

No statistical analyses for this end point

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (cross-reactive serotypes).

Top of page

End point title

Number of nasopharyngeal swabs with S.pneumoniae (cross-reactive serotypes). ^[11]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Swabs
Pre (N=330,407)	13	15
M1 (N=332,408)	19	22
M3 (N=332,408)	21	27
M7 (N=334,406)	19	21
M12 (N=334,409)	19	18
Overall (N=336,414)	55	59

No statistical analyses for this end point

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (non-vaccine and non-cross-reactive serotypes).

Top of page

End point title

Number of nasopharyngeal swabs with S.pneumoniae (non-vaccine and non-cross-reactive serotypes). ^[12]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Swabs
Pre (N=330,407)	26	27
M1 (N=332,408)	30	42
M3 (N=332,408)	32	45
M7 (N=334,406)	29	42
M12 (N=334,409)	22	39
Overall (N=336,414)	82	111

No statistical analyses for this end point

Secondary: Number of nasopharyngeal swabs with H. influenzae.

Top of page

End point title

Number of nasopharyngeal swabs with H. influenzae. ^[13]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Swabs
Pre (N=312,397)	41	48
M1 (N=318,402)	39	56
M3 (N=328,403)	34	62
M7 (N=332,403)	49	64
M12 (N=333,406)	57	46
Overall (N=336,414)	124	160

No statistical analyses for this end point

Secondary: Number of nasopharyngeal swabs with S. pneumoniae and H. influenzae.

Top of page

End point title

Number of nasopharyngeal swabs with S. pneumoniae and H. influenzae. ^[14]

End point description

End point type

Secondary

End point timeframe

Prior to vaccination(Pre), 1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Swabs
Pre (N=312,397)	19	21
M1 (N=318,402)	20	30
M3 (N=328,403)	17	31
M7 (N=332,403)	22	28
M12 (N=333,406)	22	19
Overall (N=336,414)	61	86

No statistical analyses for this end point

Secondary: Number of subjects with new acquisition associated to S. pneumoniae detected in nasopharyngeal swabs.

Top of page

End point title

Number of subjects with new acquisition associated to S. pneumoniae detected in nasopharyngeal swabs. ^[15]

End point description

End point type

Secondary

End point timeframe

1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Subjects
M1 (N=332,408)	43	56
M3 (N=332,408)	63	76
M7 (N=334,406)	70	73
M12 (N=334,409)	65	70
Overall (N=336,414)	161	195

No statistical analyses for this end point

Secondary: Number of subjects with new acquisition associated to H. influentzae detected in nasopharyngeal swabs.

Top of page

End point title

Number of subjects with new acquisition associated to H. influentzae detected in nasopharyngeal swabs. ^[16]

End point description

End point type

Secondary

End point timeframe

1 month post-vaccination (M1), 3 months post-vaccination (M3), 7 months post-vaccination (M7), 12 months post-vaccination (M12) and across all time points (Overall).

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results were tabulated on pooled primed groups and on unprimed group.

End point values	Unprimed Group	Pooled primed Group
Number of subjects analysed	336	414
Units: Subjects
M1 (N=318,402)	21	32
M3 (N=328,403)	22	40
M7 (N=332,403)	37	42
M12 (N=333,406)	39	35
Overall (N=336,414)	104	129

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Solicited symptoms: 4-day (Days 0- 3) follow-up periods after vaccination; Unsolicited AEs: 31-day (Days 0-30) follow-up periods after vaccination; SAEs: Entire study period (Months 0-12).

Adverse event reporting additional description

Unsolicited AEs values are presented for the 10Pn group: specific results for the subgroups 10PN-pre and 10Pn-post are not available and replaced with "0". Note: the occurrences (all) numbers were not calculated during the analysis: data entered are equal to the subject affected numbers.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

12.0

Reporting group title

10Pn-PD-DiT/ Paracetamol Group

Reporting group description

Reporting group title

10Pn-PD-DiT Group

Reporting group description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine with prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. Before the implementation of protocol amendment 3: as originally planned, subjects should receive paracetamol with the booster vaccines. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none. It was therefore decided to discontinue the administration of paracetamol during the booster phase, e.g. during the enrollment in the present study for the subjects belonging to this group.

Reporting group title

10Pn-Pre Group

Reporting group description

Subjects were vaccinated with 3 primary vaccination doses of 10Pn vaccine without prophylactic administration of paracetamol in study 10PN-PD-DIT-010 (107017), and received in this study at 12-15 months of age a booster dose of 10Pn vaccine, co-administered with Infanrix™ hexa without prophylactic antipyretic treatment. From the primary vaccination study results, it was revealed that the immune response induced by the 10Pn vaccine was significantly lower in subjects receiving paracetamol compared to those receiving none. To avoid introducing a bias in the study results because of the split of 2 groups: 10PN-PD-DIT Paracetamol and 10PN-PD-DIT groups at that point in time, the control 10Pn Group was also divided into 2 subgroups:10Pn-Pre(subjects enrolled before protocol amendment 3) and 10Pn-Post (subjects enrolled after protocol amendment 3).

Reporting group title

10Pn-Post Group

Reporting group description

Reporting group title

10Pn Group

Reporting group description

pooled group with subjects from both 10Pn-Pre and 10Pn-Post Groups.

Reporting group title

Unprimed Group

Reporting group description

Age-matched pneumococcal vaccine unprimed group receiving a single dose of meningococcal conjugate vaccine GSK134612 co-administered with DTPa-HBV-IPV/Hib (Infanrix hexa).

Serious adverse events	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	10Pn Group	Unprimed Group
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 178 (7.30%)	5 / 27 (18.52%)	13 / 172 (7.56%)	4 / 37 (10.81%)	17 / 209 (8.13%)	30 / 336 (8.93%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Injury, poisoning and procedural complications
Concussion
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	2 / 172 (1.16%)	0 / 37 (0.00%)	2 / 209 (0.96%)	3 / 336 (0.89%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	2 / 178 (1.12%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	2 / 336 (0.60%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body trauma
subjects affected / exposed	1 / 178 (0.56%)	1 / 27 (3.70%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Accidental exposure
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	1 / 37 (2.70%)	1 / 209 (0.48%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Caustic injury
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngeal injury
subjects affected / exposed	0 / 178 (0.00%)	1 / 27 (3.70%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Poisoning
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Arteriovenous malformation
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	2 / 336 (0.60%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Testicular retraction
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Dyspepsia
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	1 / 178 (0.56%)	1 / 27 (3.70%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillar disorder
subjects affected / exposed	0 / 178 (0.00%)	1 / 27 (3.70%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermal cyst
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 178 (0.56%)	1 / 27 (3.70%)	2 / 172 (1.16%)	1 / 37 (2.70%)	3 / 209 (1.44%)	4 / 336 (1.19%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Laryngitis
subjects affected / exposed	2 / 178 (1.12%)	1 / 27 (3.70%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	4 / 336 (1.19%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	2 / 172 (1.16%)	0 / 37 (0.00%)	2 / 209 (0.96%)	2 / 336 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	0 / 172 (0.00%)	1 / 37 (2.70%)	1 / 209 (0.48%)	3 / 336 (0.89%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 178 (0.00%)	1 / 27 (3.70%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	4 / 336 (1.19%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	4 / 336 (1.19%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	1 / 37 (2.70%)	1 / 209 (0.48%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	2 / 336 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
subjects affected / exposed	1 / 178 (0.56%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Salmonellosis
subjects affected / exposed	0 / 178 (0.00%)	1 / 27 (3.70%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vulvitis
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	0 / 172 (0.00%)	0 / 37 (0.00%)	0 / 209 (0.00%)	1 / 336 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 178 (0.00%)	0 / 27 (0.00%)	1 / 172 (0.58%)	0 / 37 (0.00%)	1 / 209 (0.48%)	0 / 336 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	10Pn-PD-DiT/ Paracetamol Group	10Pn-PD-DiT Group	10Pn-Pre Group	10Pn-Post Group	10Pn Group	Unprimed Group
Total subjects affected by non serious adverse events
subjects affected / exposed	91 / 178 (51.12%)	17 / 27 (62.96%)	105 / 172 (61.05%)	19 / 37 (51.35%)	124 / 209 (59.33%)	147 / 336 (43.75%)
General disorders and administration site conditions
Pain
alternative assessment type: Systematic
subjects affected / exposed	54 / 178 (30.34%)	10 / 27 (37.04%)	79 / 172 (45.93%)	19 / 37 (51.35%)	98 / 209 (46.89%)	114 / 336 (33.93%)
occurrences all number	54	10	79	19	98	114
Redness
alternative assessment type: Systematic
subjects affected / exposed	89 / 178 (50.00%)	9 / 27 (33.33%)	74 / 172 (43.02%)	12 / 37 (32.43%)	86 / 209 (41.15%)	146 / 336 (43.45%)
occurrences all number	89	9	74	12	86	146
Swelling
alternative assessment type: Systematic
subjects affected / exposed	52 / 178 (29.21%)	8 / 27 (29.63%)	50 / 172 (29.07%)	13 / 37 (35.14%)	63 / 209 (30.14%)	71 / 336 (21.13%)
occurrences all number	52	8	50	13	63	71
Drowsiness
subjects affected / exposed	91 / 178 (51.12%)	11 / 27 (40.74%)	84 / 172 (48.84%)	18 / 37 (48.65%)	102 / 209 (48.80%)	146 / 336 (43.45%)
occurrences all number	91	11	84	18	102	146
Fever/(rectal temperature ≥ 38.0°C)
alternative assessment type: Systematic
subjects affected / exposed	64 / 178 (35.96%)	14 / 27 (51.85%)	100 / 172 (58.14%)	16 / 37 (43.24%)	116 / 209 (55.50%)	146 / 336 (43.45%)
occurrences all number	64	14	100	16	116	146
Irritability
alternative assessment type: Systematic
subjects affected / exposed	86 / 178 (48.31%)	17 / 27 (62.96%)	105 / 172 (61.05%)	19 / 37 (51.35%)	124 / 209 (59.33%)	147 / 336 (43.75%)
occurrences all number	86	17	105	19	124	147
Loss of appetite
subjects affected / exposed	47 / 178 (26.40%)	8 / 27 (29.63%)	46 / 172 (26.74%)	10 / 37 (27.03%)	56 / 209 (26.79%)	88 / 336 (26.19%)
occurrences all number	47	8	46	10	56	88
Infections and infestations
Nasopharyngitis
subjects affected / exposed	2 / 178 (1.12%)	3 / 27 (11.11%)	0 / 172 (0.00%)	0 / 37 (0.00%)	5 / 209 (2.39%)	0 / 336 (0.00%)
occurrences all number	2	3	0	0	5	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

18 Apr 2007

The amendment is written in response to comments given by the Czech Republic Authorities. In addition the following changes have been included : • Change in Central Study Coordinator. • The microbiological procedures to assess the occurrence of other bacteriological pathogens have been described in more detail. • To avoid confusion regarding the administration of DTPa-HBV-IPV/Hib vaccine, this section has been rewritten. • Clarification of attribution of subject and treatment numbers to the subjects in the unprimed group. • Estimation of sample size of unprimed group has been clarified. • Analysis of carriage has been updated in accordance with the microbiological procedures used to assess the occurrence of other bacteriological pathogens. • Update of literature references.

19 Jul 2007

As groups were defined as primed and unprimed with regard to pneumococcal vaccination it seemed obvious that the unprimed group was supposed not to have been vaccinated with any pneumococcal vaccine before enrolment. To ensure that the subjects that had previously received a pneumococcal vaccine would not be enrolled or that subjects that received a pneumococcal vaccine during the study would be eliminated, this criterium was added. • Serology testing with regard to pneumococcal antibodies for the unprimed group was considered scientifically relevant to set a baseline for the interpretation of the carriage results of the primed group. In addition serology testing with regard to antibodies against the co-administered vaccine was added for both groups. • As GSK Biologicals is considering an extension study, the possibility to participate in a long-term follow-up study should be addressed at the concluding visit of this study. • For the unprimed group the power to detect group difference in carriage of S. pneumoniae and H. influenzae was adjusted to better reflect what was already observed in POET (study Undeca-Pn-010 [347414/010]) • Update of literature references.

24 Sep 2007

The results of the primary vaccination study 10PN-PD-DIT-010 have shown that paracetamol (acetaminophen) given as a prophylactic treatment at the time of vaccination significantly reduced the incidence of febrile reactions following vaccination with GSK Biologicals. 10-valent pneumococcal conjugate vaccine coadministered with DTPa-HBV-IPV/Hib (Infanrix hexa) vaccine at 3, 4 and 5 months of age and GSK Biologicals. oral live attenuated HRV (Rotarix) vaccine at 3 and 4 months of age [41.6% of subjects experienced fever ≥ 38°C (rectal temperature) in the antipyretic group versus 66.1% of subjects in the non-antipyretic group]. In addition, the study also showed that the use of prophylactic paracetamol seemed to interfere with the primary immune response. The reason for a decrease in the immune response may relate to a reduction of the inflammatory signals that attract the dendritic cells to the injection sites, such that fewer and/or less activated dendritic cells reach the draining lymph nodes, resulting in a reduced B cell stimulation and lower antibody concentrations. In addition, it cannot be excluded that the induction of memory cells (T cells and B cells) is also affected by the prophylactic administration of paracetamol, which may prevent children from developing an adequate booster immune response. Therefore, the prophylactic administration of paracetamol during the booster phase will be stopped. Approximately 50% of the subjects were already enrolled and vaccinated according to the protocol (with or without prophylactic administration of paracetamol). The immune responses of all vaccinated children will be carefully monitored and the need for additional doses will be evaluated after the booster dose. Additional doses of vaccines will be made available, when necessary.

18 Jan 2008

• Details about the planned interim analysis. • Planning of a second interim analysis. • Correction in the EudraCT number. In addition, strikethrough text related to previous amendments has been removed. Furthermore, all bold italic text related to previous amendments has been changed into normal text. Those additional changes are documented below following the changes for which this fourth amendment has been developed.

03 Feb 2009

The study protocol has been amended for the following reason: - The availability of the results of the microbiological assessments on nasopharyngeal carriage up to Visit 3 has been delayed. Therefore there is a need to cancel second interim analysis on carriage based on the time point V3 and to involve additional other laboratories designated by GSK Biologicals to speed up the microbiological work. • The fact that microbial assessments can be performed not only at the regional laboratory in the Czech Republic, but also at a laboratory designated by GSK Biologicals, was added. • The planned second interim analysis will not be performed anymore.

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Prophylactic antipyretic treatment in children receiving booster dose of pneumococcal vaccine GSK1024850A and Infanrix hexa™ and assessment of impact of pneumococcal vaccination on nasopharyngeal carriage.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects reported with core fever (rectal temperature) ≥38.0 degrees Celsius (ºC).

Primary: Number of subjects reported with core fever (rectal temperature) ≥38.0 degrees Celsius (ºC).

Secondary: Number of subjects reported with core fever (rectal temperature) > 39.0°C.

Secondary: Number of subjects reported with core fever (rectal temperature) > 39.0°C.

Secondary: Number of subjects reported with any and Grade 3 solicited local symptoms.

Secondary: Number of subjects reported with any and Grade 3 solicited local symptoms.

Secondary: Number of subjects reported with any and Grade 3 solicited general symptoms.

Secondary: Number of subjects reported with any and Grade 3 solicited general symptoms.

Secondary: Number of subjects reported with unsolicited adverse events (AEs).

Secondary: Number of subjects reported with unsolicited adverse events (AEs).

Secondary: Number of subjects reported with serious adverse events (SAEs).

Secondary: Number of subjects reported with serious adverse events (SAEs).

Secondary: Number of subjects reported with AEs resulting in rash, new onset of chronic illness (NOCI), emergency room (ER) visits and non-routine physician office visits.

Secondary: Number of subjects reported with AEs resulting in rash, new onset of chronic illness (NOCI), emergency room (ER) visits and non-routine physician office visits.

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL.

Secondary: Number of subjects with antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F) ≥ 0.2 μg/mL.

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F).

Secondary: Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F).

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F.

Secondary: Concentrations of antibodies against protein D (Anti-PD).

Secondary: Concentrations of antibodies against protein D (Anti-PD).

Secondary: Antibody concentrations against pneumococcal serotypes 6A and 19A (anti-6A and 19A).

Secondary: Antibody concentrations against pneumococcal serotypes 6A and 19A (anti-6A and 19A).

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A.

Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A.

Secondary: Number of subjects with titers ≥ 1:8 and 1:128 for meningococcal polysaccharides A , C, W-135 and Y serum bactericidal antibodies, using baby rabbit complement for assay (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) in the unprimed Group.

Secondary: Number of subjects with titers ≥ 1:8 and 1:128 for meningococcal polysaccharides A , C, W-135 and Y serum bactericidal antibodies, using baby rabbit complement for assay (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) in the unprimed Group.

Secondary: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers in the unprimed Group.

Secondary: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY titers in the unprimed Group.

Secondary: Number of subjects with anti-polysaccharide N. meningitidis serogroup A (anti-PSA), C (anti-PSC), W (anti-PSW-135) and Y (anti-PSY) ≥ 0.3 μg/mL and 2.0 μg/mL in the unprimed Group.

Secondary: Number of subjects with anti-polysaccharide N. meningitidis serogroup A (anti-PSA), C (anti-PSC), W (anti-PSW-135) and Y (anti-PSY) ≥ 0.3 μg/mL and 2.0 μg/mL in the unprimed Group.

Secondary: Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibody concentrations in the unprimed Group.

Secondary: Anti-PSA, anti-PSC, anti-PSW-135 and anti-PSY antibody concentrations in the unprimed Group.

Secondary: Anti-tetanus toxoids (anti-T) antibody concentrations in the unprimed Group.

Secondary: Anti-tetanus toxoids (anti-T) antibody concentrations in the unprimed Group.

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in the unprimed Group.

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations in the unprimed Group.

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T).

Secondary: Concentrations of antibodies against diphtheria and tetanus toxoids (anti-D and T).

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations.

Secondary: Anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations.

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations (Month1).

Secondary: Anti-hepatitis B surface antigen (anti-HBs) antibody concentrations (Month1).

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations.

Secondary: Anti-polyribosyl-ribitol phosphate (anti-PRP) antibody concentrations.

Secondary: Anti-Polio types 1, 2 and 3 titers (Month 1).

Secondary: Anti-Polio types 1, 2 and 3 titers (Month 1).

Secondary: Anti-HBs antibody concentrations (Month 12).

Secondary: Anti-HBs antibody concentrations (Month 12).

Secondary: Anti-Polio type 1, 2 and 3 titers (Month 12).

Secondary: Anti-Polio type 1, 2 and 3 titers (Month 12).

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (vaccine serotypes).

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (vaccine serotypes).

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (cross-reactive serotypes).

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (cross-reactive serotypes).

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (non-vaccine and non-cross-reactive serotypes).

Secondary: Number of nasopharyngeal swabs with S.pneumoniae (non-vaccine and non-cross-reactive serotypes).

Secondary: Number of nasopharyngeal swabs with H. influenzae.

Secondary: Number of nasopharyngeal swabs with H. influenzae.

Secondary: Number of nasopharyngeal swabs with S. pneumoniae and H. influenzae.

Secondary: Number of nasopharyngeal swabs with S. pneumoniae and H. influenzae.

Secondary: Number of subjects with new acquisition associated to S. pneumoniae detected in nasopharyngeal swabs.

Secondary: Number of subjects with new acquisition associated to S. pneumoniae detected in nasopharyngeal swabs.

Secondary: Number of subjects with new acquisition associated to H. influentzae detected in nasopharyngeal swabs.

Secondary: Number of subjects with new acquisition associated to H. influentzae detected in nasopharyngeal swabs.

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
Prophylactic antipyretic treatment in children receiving booster dose of pneumococcal vaccine GSK1024850A and Infanrix hexa™ and assessment of impact of pneumococcal vaccination on nasopharyngeal carriage.