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Clinical Trial Results:
A phase III, open, controlled study to evaluate the immunogenicity, safety and reactogenicity of GSK Biologicals’ 10- valent pneumococcal conjugate vaccine administered to children with sickle cell disease between 8 weeks and 2 years of age, as compared to healthy children.

Summary
EudraCT number	2012-000254-64
Trial protocol	Outside EU/EEA
Global end of trial date	23 May 2013

Results information
Results version number	v2
This version publication date	28 Apr 2016
First version publication date	25 Jul 2015
Other versions	v1 , v3
Version creation reason	New data added to full data set Data for secondary endpoints have been added.

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

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Trial information

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Sponsor protocol code

114056

ISRCTN number

US NCT number

NCT01175083

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, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-000673-PIP01-09

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

04 Aug 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 May 2013

Was the trial ended prematurely?

Main objective of the trial

To assess the immunogenicity of GSK Biologicals’ 10-valent pneumococcal conjugate vaccine when co-administered with DTPw-HBV/Hib and OPV vaccines in children with sickle cell disease, one month after completion of the 3-dose primary vaccination course before 6 months of age

Protection of trial subjects

All subjects were supervised after vaccination/product administration with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jun 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Burkina Faso: 300

Worldwide total number of subjects

300

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

300

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

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

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

<6S Group

Arm description

Children below 6 months of age with sickle cell disease, receiving a 3-dose primary vaccination with 10Pn-PD-DiT vaccine at approximately 8-12-16 weeks of age and booster vaccination at 9-10 months of age. Subjects received DTPw-HBV/Hib + OPV as co-administered vaccines. The allowable intervals between the primary vaccination doses were 28-42 days.

Arm type

Experimental

Investigational medicinal product name

GSK1024850A (Synflorix™)

Investigational medicinal product code

Other name

GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 intramuscular vaccine doses were administered intramuscularly into the right thigh.

Investigational medicinal product name

Tritanrix-HB

Investigational medicinal product code

Other name

DTPw-HBV

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular injection, 4 doses in the left thigh.

Investigational medicinal product name

Polio Sabin

Investigational medicinal product code

Other name

OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

4 doses administered orally.

Investigational medicinal product name

Hiberix™

Investigational medicinal product code

Other name

Hib

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

White frozen dried pellet in monodose vial to be reconstituted with DTPw-HBV vaccine, intramuscular injection 4 doses in the left thigh.

<6NS Group

Arm description

Healthy children below 6 months of age, receiving a 3-dose primary vaccination with 10Pn-PD-DiT vaccine at approximately 8-12-16 weeks of age and booster vaccination at 9-10 months of age. Subjects received DTPw-HBV/Hib + OPV as co-administered vaccines. The allowable intervals between the primary vaccination doses were 28-42 days.

Arm type

Active comparator

Investigational medicinal product name

GSK1024850A (Synflorix™)

Investigational medicinal product code

Other name

GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 intramuscular vaccine doses were administered intramuscularly into the right thigh.

Investigational medicinal product name

Tritanrix-HB

Investigational medicinal product code

Other name

DTPw-HB

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular injection, 4 doses in the left thigh.

Investigational medicinal product name

Polio Sabin

Investigational medicinal product code

Other name

OPV

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

4 doses administered orally.

Investigational medicinal product name

Hiberix™

Investigational medicinal product code

Other name

Hib

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

White frozen dried pellet in monodose vial to be reconstituted with DTPw-HBV vaccine, intramuscular injection 4 doses in the left thigh.

7-11S Group

Arm description

Children between 7-11 months of age with sickle cell disease, receiving a 2-dose primary vaccination with 10Pn-PD-DiT vaccine starting at 7-11 months of age with an interval of at least 4 weeks (28-42 days) between primary doses. Subjects received a booster after an interval of 2 to 4 months since the previous dose.

Arm type

Experimental

Investigational medicinal product name

GSK1024850A (Synflorix™)

Investigational medicinal product code

Other name

GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 intramuscular vaccine doses were administered intramuscularly into the right thigh.

7-11NS Group

Arm description

Healthy children between 7-11 months of age, receiving a 2-dose primary vaccination with 10Pn-PD-DiT vaccine starting at 7-11 months of age with an interval of at least 4 weeks (28-42 days) between primary doses. Subjects received a booster after an interval of 2 to 4 months since the previous dose.

Arm type

Active comparator

Investigational medicinal product name

GSK1024850A (Synflorix™)

Investigational medicinal product code

Other name

GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 intramuscular vaccine doses were administered intramuscularly into the right thigh.

12-23S Group

Arm description

Children between 12-23 months of age with sickle cell disease, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Arm type

Experimental

Investigational medicinal product name

GSK1024850A (Synflorix™)

Investigational medicinal product code

Other name

GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 intramuscular vaccine doses were administered intramuscularly into the right thigh.

12-23NS Group

Arm description

Healthy children between 12-23 months of age, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Arm type

Active comparator

Investigational medicinal product name

GSK1024850A (Synflorix™)

Investigational medicinal product code

Other name

GSK Biologicals' 10-valent pneumococcal polysaccharide and non-typeable Haemophilus influenzae (H. influenzae) protein D conjugate vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 intramuscular vaccine doses were administered intramuscularly into the right thigh.

Number of subjects in period 1	<6S Group	<6NS Group	7-11S Group	7-11NS Group	12-23S Group	12-23NS Group
Started	50	50	50	50	50	50
Completed	49	49	49	49	50	47
Not completed	1	1	1	1	0	3
Adverse event, serious fatal	-	-	1	-	-	-
Consent withdrawn by subject	-	-	-	1	-	2
Not coming back for booster vaccination	1	1	-	-	-	-
Lost to follow-up	-	-	-	-	-	1

Baseline characteristics

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Reporting group title

<6S Group

Reporting group description

Reporting group title

<6NS Group

Reporting group description

Reporting group title

7-11S Group

Reporting group description

Reporting group title

7-11NS Group

Reporting group description

Reporting group title

12-23S Group

Reporting group description

Children between 12-23 months of age with sickle cell disease, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Reporting group title

12-23NS Group

Reporting group description

Healthy children between 12-23 months of age, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Reporting group values	<6S Group	<6NS Group	7-11S Group	7-11NS Group	12-23S Group	12-23NS Group	Total
Number of subjects	50	50	50	50	50	50	300
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	50	50	50	50	50	50	300
Gender categorical
Units: Subjects
Female	21	29	26	32	15	24	147
Male	29	21	24	18	35	26	153

End points

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Reporting group title

<6S Group

Reporting group description

Reporting group title

<6NS Group

Reporting group description

Reporting group title

7-11S Group

Reporting group description

Reporting group title

7-11NS Group

Reporting group description

Reporting group title

12-23S Group

Reporting group description

Children between 12-23 months of age with sickle cell disease, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Reporting group title

12-23NS Group

Reporting group description

Healthy children between 12-23 months of age, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Primary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - <6S and <6NS groups.

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End point title

Concentrations of antibodies against Vaccine Pneumococcal Serotypes - <6S and <6NS groups. ^[1] ^[2]

End point description

Antibodies assessed for this outcome measure were those against the vaccine 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). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Primary outcome variables correspond to Results at Month 3.

End point type

Primary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	48	46
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 [Month 0] (N=46,42)	0.09 (0.06 to 0.12)	0.09 (0.06 to 0.12)
Anti-1 [Month 3] (N=48,46)	3.51 (2.77 to 4.44)	3.63 (2.91 to 4.53)
Anti-1 [Month 8] (N=44,38)	0.67 (0.54 to 0.84)	0.69 (0.52 to 0.9)
Anti-1 [Month 9] (N=44,38)	5.34 (4.07 to 7.02)	5.14 (3.52 to 7.5)
Anti-4 [Month 0] (N=48,45)	0.04 (0.03 to 0.06)	0.06 (0.04 to 0.08)
Anti-4 [Month 3] (N=47,46)	4.25 (3.18 to 5.67)	3.51 (2.73 to 4.51)
Anti-4 [Month 8] (N=44,38)	1.2 (0.91 to 1.59)	1.08 (0.77 to 1.52)
Anti-4 [Month 9] (N=44,38)	7.04 (5.53 to 8.97)	6.02 (4.4 to 8.24)
Anti-5 [Month 0] (N=48,46)	0.06 (0.05 to 0.09)	0.07 (0.06 to 0.1)
Anti-5 [Month 3] (N=47,46)	5.15 (4.07 to 6.51)	5.94 (4.91 to 7.18)
Anti-5 [Month 8] (N=44,38)	1.13 (0.87 to 1.47)	1.23 (0.93 to 1.63)
Anti-5 [Month 9] (N=43,37)	6.3 (4.94 to 8.04)	6.91 (4.92 to 9.73)
Anti-6B [Month 0] (N=47,40)	0.07 (0.05 to 0.09)	0.11 (0.07 to 0.18)
Anti-6B [Month 3] (N=48,46)	1.29 (0.83 to 1.99)	1.13 (0.74 to 1.72)
Anti-6B [Month 8] (N=44,38)	1.94 (1.55 to 2.44)	1.62 (1.25 to 2.09)
Anti-6B [Month 9] (N=44,37)	5.07 (4.16 to 6.18)	5 (3.71 to 6.74)
Anti-7F [Month 0] (N=47,44)	0.08 (0.06 to 0.11)	0.13 (0.09 to 0.19)
Anti-7F [Month 3] (N=48,46)	4.91 (3.84 to 6.28)	4.28 (3.49 to 5.26)
Anti-7F [Month 8] (N=44,38)	1.83 (1.41 to 2.37)	1.57 (1.21 to 2.05)
Anti-7F [Month 9] (N=44,38)	9.03 (7.18 to 11.37)	8.19 (6.18 to 10.86)
Anti-9V [Month 0] (N=47,44)	0.12 (0.08 to 0.16)	0.12 (0.09 to 0.16)
Anti-9V [Month 3] (N=47,46)	4.56 (3.51 to 5.92)	4.59 (3.7 to 5.7)
Anti-9V [Month 8] (N=44,38)	1.61 (1.17 to 2.21)	1.44 (1.13 to 1.82)
Anti-9V [Month 9] (N=44,38)	8.19 (6.61 to 10.14)	7.95 (5.94 to 10.63)
Anti-14 [Month 0] (N=48,44)	0.77 (0.53 to 1.12)	0.65 (0.42 to 0.99)
Anti-14 [Month 3] (N=46,46)	4.3 (3.08 to 6)	5.95 (4.27 to 8.29)
Anti-14 [Month 8] (N=44,38)	2.58 (1.9 to 3.51)	2.1 (1.32 to 3.34)
Anti-14 [Month 9] (N=44,38)	8.66 (6.91 to 10.85)	7.43 (4.72 to 11.7)
Anti-18C [Month 0] (N=48,45)	0.13 (0.1 to 0.18)	0.13 (0.09 to 0.18)
Anti-18C [Month 3] (N=47,45)	14.6 (11.01 to 19.36)	11.33 (8.47 to 15.17)
Anti-18C [Month 8] (N=44,38)	3.82 (2.97 to 4.92)	3.16 (2.32 to 4.31)
Anti-18C [Month 9] (N=44,38)	16.52 (12.81 to 21.32)	16.74 (12.98 to 21.58)
Anti-19F [Month 0] (N=48,45)	0.34 (0.23 to 0.51)	0.3 (0.21 to 0.44)
Anti-19F [Month 3] (N=47,46)	11.87 (9.05 to 15.57)	9.78 (7.01 to 13.64)
Anti-19F [Month 8] (N=44,38)	3.31 (2.51 to 4.38)	3.27 (2.21 to 4.84)
Anti-19F [Month 9] (N=44,38)	10.96 (8.37 to 14.34)	11.27 (8.18 to 15.54)
Anti-23F [Month 0] (N=48,43)	0.13 (0.09 to 0.2)	0.1 (0.07 to 0.14)
Anti-23F [Month 3] (N=48,46)	1.32 (0.9 to 1.93)	1.41 (0.95 to 2.11)
Anti-23F [Month 8] (N=44,38)	0.67 (0.48 to 0.94)	0.77 (0.51 to 1.17)
Anti-23F [Month 9] (N=44,38)	4.86 (3.34 to 7.07)	4.54 (2.7 to 7.62)

No statistical analyses for this end point

Primary: Concentrations of Antibodies against Protein D (PD) - <6S and <6NS groups.

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End point title

Concentrations of Antibodies against Protein D (PD) - <6S and <6NS groups. ^[3] ^[4]

End point description

Anti-protein D (Anti-PD) antibody concentrations by Enzyme-Linked Immunosorbent Assay (ELISA) were calculated, expressed as geometric mean concentrations (GMCs) in ELISA unit per milli-liter (EL.U/mL) and tabulated. The seropositivity cut-off for the assay was ≥ 100 EL.U/mL. Antibody concentrations < 100 EL.U/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation. Primary outcome variables correspond to Results at Month 3.

End point type

Primary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	47	46
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD [Month 0] (N=47,46)	64.75 (50.56 to 82.92)	70.97 (53.71 to 93.78)
Anti-PD [Month 3] (N=47,46)	2789.09 (2313.89 to 3361.87)	3065.4 (2530.54 to 3713.31)
Anti-PD [Month 8] (N=44,38)	859.87 (681.75 to 1084.52)	840.88 (641.5 to 1102.23)
Anti-PD [Month 9] (N=44,38)	2871.72 (2338.21 to 3526.96)	3137.87 (2459.92 to 4002.68)

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination -<6S and <6NS Groups)

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End point title

Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination -<6S and <6NS Groups) ^[5]

End point description

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site.

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	50	50
Units: Subjects
Any Pain, Dose 1	8	12
Grade 3 Pain, Dose 1	0	0
Any Redness, Dose 1	0	0
Grade 3 Redness, Dose 1	0	0
Any Swelling, Dose 1	0	0
Grade 3 Swelling, Dose 1	0	0
Any Pain, Dose 2	7	7
Grade 3 Pain, Dose 2	0	0
Any Redness, Dose 2	0	0
Grade 3 Redness, Dose 2	0	0
Any Swelling, Dose 2	0	1
Grade 3 Swelling, Dose 2	0	0
Any Pain, Dose 3	4	6
Grade 3 Pain, Dose 3	0	0
Any Redness, Dose 3	0	0
Grade 3 Redness, Dose 3	0	0
Any Swelling, Dose 3	0	0
Grade 3 Swelling, Dose 3	0	0
Any Pain, Across	17	23
Grade 3 Pain, Across	0	0
Any Redness, Across	0	0
Grade 3 Redness, Across	0	0
Any Swelling, Across	0	1
Grade 3 Swelling, Across	0	0

No statistical analyses for this end point

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination -<6S and <6NS Groups)

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End point title

Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination -<6S and <6NS Groups) ^[6]

End point description

Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as rectal temperature equal to or above 38 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 40.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	50	50
Units: Subjects
Any Drowsiness, Dose 1	0	0
Grade 3 Drowsiness, Dose 1	0	0
Related Drowsiness, Dose 1	0	0
Any Irritability, Dose 1	0	2
Grade 3 Irritability, Dose 1	0	0
Related Irritability, Dose 1	0	0
Any Loss of appetite, Dose 1	0	0
Grade 3 Loss of appetite, Dose 1	0	0
Related Loss of appetite, Dose 1	0	0
Any Fever, Dose 1	34	31
Grade 3 Fever, Dose 1	0	0
Related Fever, Dose 1	31	29
Any Drowsiness, Dose 2	0	0
Grade 2 Drowsiness, Dose 2	0	0
Related Drowsiness, Dose 2	0	0
Any Irritability, Dose 2	0	0
Grade 3 Irritability, Dose 2	0	0
Related Irritability, Dose 2	0	0
Any Loss of appetite, Dose 2	0	0
Grade 3 Loss of appetite, Dose 2	0	0
Related Loss of appetite, Dose 2	0	0
Any Fever, Dose 2	40	30
Grade 3 Fever, Dose 2	0	0
Related Fever, Dose 2	38	28
Any Drowsiness, Dose 3	0	0
Grade 3 Drowsiness, Dose 3	0	0
Related Drowsiness, Dose 3	0	0
Any Irritability, Dose 3	3	4
Grade 3 Irritability, Dose 3	0	0
Related Irritability, Dose 3	3	3
Any Loss of appetite, Dose 3	0	1
Grade 3 Loss of appetite, Dose 3	0	0
Related Loss of appetite, Dose 3	0	0
Any Fever, Dose 3	30	30
Grade 3 Fever, Dose 3	0	0
Related Fever, Dose 3	26	28
Any Drowsiness, Across Doses	0	0
Grade 3 Drowsiness, Across Doses	0	0
Related Drowsiness, Across Doses	0	0
Any Irritability, Across Doses	3	6
Grade 3 Irritability, Across Doses	0	0
Related Irritability, Across Doses	3	3
Any Loss of appetite, Across Doses	0	1
Grade 3 Loss of appetite, Across Doses	0	0
Related Loss of appetite, Across Doses	0	0
Any Fever, Across Doses	48	43
Grade 3 Fever, Across Doses	0	0
Related Fever, Across Doses	46	43

No statistical analyses for this end point

Secondary: Number of subjects with any unsolicited adverse events (AEs) (<6S, <6NS, 7-11S, 7-11NS Groups)

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End point title

Number of subjects with any unsolicited adverse events (AEs) (<6S, <6NS, 7-11S, 7-11NS Groups) ^[7]

End point description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

End point type

Secondary

End point timeframe

Within 31 days (Days 0-30) post primary and booster 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 are provided only for 4 groups as timeframe has been defined specifically for those 4 groups.

End point values	<6S Group	<6NS Group	7-11S Group	7-11NS Group
Number of subjects analysed	50	50	50	50
Units: Subjects
Any AEs post primary vaccination [N=50,50,50,50]	37	34	32	37
Any AEs post-booster vaccination [N=49,49,50,50]	8	17	18	12

No statistical analyses for this end point

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

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End point title

Number of subjects with serious adverse events (SAEs) (all groups).

End point description

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

End point type

Secondary

End point timeframe

During the entire study period.

End point values	<6S Group	<6NS Group	7-11S Group	7-11NS Group	12-23S Group	12-23NS Group
Number of subjects analysed	50	50	50	50	50	50
Units: Subjects
Any SAEs	3	9	3	4	2	2

No statistical analyses for this end point

Secondary: Number of subjects with any unsolicited adverse events (AEs) (12-23S and 12-23NS Groups)

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End point title

Number of subjects with any unsolicited adverse events (AEs) (12-23S and 12-23NS Groups) ^[8]

End point description

End point type

Secondary

End point timeframe

Within the 31-day (Days 0-30) post vaccination period.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	50	50
Units: Subjects
Any AE(s)	23	25

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Booster vaccination - <6S, <6NS, 7-11S, 7-11NS Groups).

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End point title

Number of subjects with any and Grade 3 solicited local symptoms (Booster vaccination - <6S, <6NS, 7-11S, 7-11NS Groups). ^[9]

End point description

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-booster vaccination period.

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 are provided only for 4 groups as timeframe has been defined specifically for those 4 groups.

End point values	<6S Group	<6NS Group	7-11S Group	7-11NS Group
Number of subjects analysed	49	49	50	50
Units: Subjects
Any Pain	11	6	3	0
Grade 3 Pain	0	0	0	0
Any Redness	0	0	0	0
Grade 3 Redness	0	0	0	0
Any Swelling	1	0	1	0
Grade 3 Swelling	0	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited local symptoms.(12-23S and 12-23NS Groups)

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End point title

Number of subjects with any and Grade 3 solicited local symptoms.(12-23S and 12-23NS Groups) ^[10]

End point description

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	50	50
Units: Subjects
Any Pain, Dose 1 [N=50,50]	9	6
Grade 3 Pain, Dose 1 [N=50,50]	0	0
Any Redness, Dose 1 [N=50,50]	0	0
Grade 3 Redness, Dose 1 [N=50,50]	0	0
Any Swelling, Dose 1 [N=50,50]	1	1
Grade 3 Swelling, Dose 1 [N=50,50]	0	0
Any Pain, Dose 2 [N=50,48]	5	3
Grade 3 Pain, Dose 2 [N=50,48]	0	0
Any Redness, Dose 2 [N=50,48]	0	0
Grade 3 Redness, Dose 2 [N=50,48]	0	0
Any Swelling, Dose 2 [N=50,48]	0	0
Grade 3 Swelling, Dose 2 [N=50,48]	0	0
Any Pain, Across Doses [N=50,50]	13	9
Grade 3 Pain, Across Doses [N=50,50]	0	0
Any Redness, Across Doses [N=50,50]	0	0
Grade 3 Redness, Across Doses [N=50,50]	0	0
Any Swelling, Across Doses [N=50,50]	1	1
Grade 3 Swelling, Across Doses [N=50,50]	0	0

No statistical analyses for this end point

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination - 7-11S and 7-11NS Groups)

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End point title

Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination - 7-11S and 7-11NS Groups) ^[11]

End point description

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	50	50
Units: Subjects
Any Drowsiness, Dose 1	0	1
Grade 3 Drowsiness, Dose 1	0	0
Related Drowsiness, Dose 1	0	1
Any Irritability, Dose 1	0	0
Grade 3 Irritability, Dose 1	0	0
Related Irritability, Dose 1	0	0
Any Loss of appetite, Dose 1	0	0
Grade 3 Loss of appetite, Dose 1	0	0
Related Loss of appetite, Dose 1	0	0
Any Fever, Dose 1	22	26
Grade 3 Fever, Dose 1	0	0
Related Fever, Dose 1	19	22
Any Drowsiness, Dose 2	0	0
Grade 3 Drowsiness, Dose 2	0	0
Related Drowsiness, Dose 2	0	0
Any Irritability, Dose 2	0	0
Grade 3 Irritability, Dose 2	0	0
Related Irritability, Dose 2	0	0
Any Loss of appetite, Dose 2	0	0
Grade 3 Loss of appetite, Dose 2	0	0
Related Loss of appetite, Dose 2	0	0
Any Fever, Dose 2	22	11
Grade 3 Fever, Dose 2	0	0
Related Fever, Dose 2	20	9
Any Drowsiness, Across Doses	0	1
Grade 3 Drowsiness, Across Doses	0	0
Related Drowsiness, Across Doses	0	1
Any Irritability, Across Doses	0	0
Grade 3 Irritability, Across Doses	0	0
Related Irritability, Across Doses	0	0
Any Loss of appetite, Across Doses	0	0
Grade 3 Loss of appetite, Across Doses	0	0
Related Loss of appetite, Across Doses	0	0
Any Fever, Across Doses	31	29
Grade 3 Fever, Across Doses	0	0
Related Fever, Across Doses	29	25

No statistical analyses for this end point

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms. (Booster vaccination – <6S, <6NS, 7-11S, 7-11NS groups)

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End point title

Number of subjects with any, Grade 3 and related solicited general symptoms. (Booster vaccination – <6S, <6NS, 7-11S, 7-11NS groups) ^[12]

End point description

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-booster vaccination period.

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 are provided only for 4 groups as timeframe has been defined specifically for those 4 groups.

End point values	<6S Group	<6NS Group	7-11S Group	7-11NS Group
Number of subjects analysed	49	49	50	50
Units: Subjects
Any Drowsiness	0	0	0	0
Grade 3 Drowsiness	0	0	0	0
Related Drowsiness	0	0	0	0
Any Irritability	6	0	0	0
Grade 3 Irritability	0	0	0	0
Related Irritability	5	0	0	0
Any Loss of appetite	0	0	0	0
Grade 3 Loss of appetite	0	0	0	0
Related Loss of appetite	0	0	0	0
Any Fever	38	31	14	13
Grade 3 Fever	0	0	0	0
Related Fever	35	28	13	13

No statistical analyses for this end point

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination – 7-11S and 7-11NS Groups)

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End point title

Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination – 7-11S and 7-11NS Groups) ^[13]

End point description

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	50	50
Units: Subjects
Any Pain, Dose 1	7	10
Grade 3 Pain, Dose 1	0	0
Any Redness, Dose 1	0	0
Grade 3 Redness, Dose 1	0	0
Any Swelling, Dose 1	0	0
Grade 3 Swelling, Dose 1	0	0
Any Pain, Dose 2	5	7
Grade 3 Pain, Dose 2	0	0
Any Redness, Dose 2	0	0
Grade 3 Redness, Dose 2	0	0
Any Swelling, Dose 2	0	1
Grade 3 Swelling, Dose 2	0	0
Any Pain, Across Doses	12	15
Grade 3 Pain, Across Doses	0	0
Any Redness, Across Doses	0	0
Grade 3 Redness, Across Doses	0	0
Any Swelling, Across Doses	0	1
Grade 3 Swelling, Across Doses	0	0

No statistical analyses for this end point

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (12-23S and 12-23NS Groups)

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End point title

Number of subjects with any, Grade 3 and related solicited general symptoms (12-23S and 12-23NS Groups) ^[14]

End point description

End point type

Secondary

End point timeframe

During the 4-day (Days 0-3) post-vaccination period following each dose and across doses.

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	50	50
Units: Subjects
Any Drowsiness, Dose 1 [N=50,50]	0	0
Grade 3 Drowsiness, Dose 1 [N=50,50]	0	0
Related Drowsiness, Dose 1 [N=50,50]	0	0
Any Irritability, Dose 1 [N=50,50]	1	0
Grade 3 Irritability, Dose 1 [N=50,50]	0	0
Related Irritability, Dose 1 [N=50,50]	1	0
Any Loss of appetite, Dose 1 [N=50,50]	0	1
Grade 3 Loss of appetite, Dose 1 [N=50,50]	0	0
Related Loss of appetite, Dose 1 [N=50,50]	0	1
Any Fever, Dose 1 [N=50,50]	21	15
Grade 3 Fever, Dose 1 [N=50,50]	0	0
Related Fever, Dose 1 [N=50,50]	21	13
Any Drowsiness, Dose 2 [N=50,48]	0	0
Grade 3 Drowsiness, Dose 2 [N=50,48]	0	0
Related Drowsiness, Dose 2 [N=50,48]	0	0
Any Irritability, Dose 2 [N=50,48]	1	0
Grade 3 Irritability, Dose 2 [N=50,48]	0	0
Related Irritability, Dose 2 [N=50,48]	1	0
Any Loss of appetite, Dose 2 [N=50,48]	0	0
Grade 3 Loss of appetite, Dose 2 [N=50,48]	0	0
Related Loss of appetite, Dose 2 [N=50,48]	0	0
Any Fever, Dose 2 [N=50,48]	12	12
Grade 3 Fever, Dose 2 [N=50,48]	0	0
Related Fever, Dose 2 [N=50,48]	10	9
Any Drowsiness, Across Doses [N=50,50]	0	0
Grade 3 Drowsiness, Across Doses [N=50,50]	0	0
Related Drowsiness, Across Doses [N=50,50]	0	0
Any Irritability, Across Doses [N=50,50]	2	0
Grade 3 Irritability, Across Doses [N=50,50]	0	0
Related Irritability, Across Doses [N=50,50]	2	0
Any Loss of appetite, Across Doses [N=50,50]	0	1
Grade 3 Loss of appetite, Across Doses [N=50,50]	0	0
Related Loss of appetite, Across Doses [N=50,50]	0	1
Any Fever, Across Doses [N=50,50]	29	20
Grade 3 Fever, Across Doses [N=50,50]	0	0
Related Fever, Across Doses [N=50,50]	28	17

No statistical analyses for this end point

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A - <6S and <6NS groups.

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End point title

Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A - <6S and <6NS groups. ^[15]

End point description

Antibodies assessed for this outcome measure were those against the cross-reactive pneumococcal serotype 6A (ANTI-6A) and 19A (ANTI-19A). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 µg/mL. Antibody concentrations < 0.05 µg/mL were given an arbitrary value of half the cut-off for the purpose of GMC calculation.

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	48	45
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A [Month 0] (N=47,41)	0.1 (0.07 to 0.14)	0.15 (0.1 to 0.23)
Anti-6A [Month 3] (N=46,43)	0.12 (0.08 to 0.17)	0.1 (0.07 to 0.13)
Anti-6A [Month 8] (N=37,30)	0.4 (0.27 to 0.61)	0.18 (0.1 to 0.3)
Anti-6A [Month 9] (N=36,29)	0.48 (0.31 to 0.74)	0.36 (0.23 to 0.55)
Anti-19A [Month 0] (N=47,44)	0.24 (0.17 to 0.36)	0.23 (0.16 to 0.33)
Anti-19A [Month 3] (N=48,45)	0.26 (0.17 to 0.39)	0.25 (0.17 to 0.37)
Anti-19A [Month 8] (N=44,38)	0.23 (0.15 to 0.37)	0.21 (0.13 to 0.35)
Anti-19A [Month 9] (N=44,37)	1.09 (0.65 to 1.83)	0.85 (0.5 to 1.43)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 7-11S and 7-11NS group.

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End point title

Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 7-11S and 7-11NS group. ^[16]

End point description

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 2), prior to (Month 3) and one month after booster vaccination (Month 4)

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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	50	50
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 [Month 0] (N=48,46)	0.03 (0.03 to 0.03)	0.04 (0.03 to 0.05)
Anti-1 [Month 2] (N=50,48)	5.48 (4.34 to 6.93)	3.99 (3.24 to 4.91)
Anti-1 [Month 3] (N=50,49)	2.68 (2.12 to 3.39)	2.44 (1.99 to 2.98)
Anti-1 [Month 4] (N=49,48)	5.51 (4.27 to 7.1)	4.92 (3.74 to 6.48)
Anti-4 [Month 0] (N=49,50)	0.03 (0.03 to 0.04)	0.03 (0.02 to 0.04)
Anti-4 [Month 2] (N=49,47)	10.88 (8.94 to 13.24)	7.55 (6 to 9.5)
Anti-4 [Month 3] (N=50,48)	5.72 (4.66 to 7.03)	4.32 (3.51 to 5.32)
Anti-4 [Month 4] (N=49,48)	9.75 (7.67 to 12.39)	7.88 (6.28 to 9.89)
Anti-5 [Month 0] (N=48,50)	0.04 (0.03 to 0.06)	0.06 (0.05 to 0.08)
Anti-5 [Month 2] (N=50,47)	6.76 (5.14 to 8.89)	4.59 (3.58 to 5.88)
Anti-5 [Month 3] (N=50,49)	3.68 (2.87 to 4.73)	3.4 (2.66 to 4.33)
Anti-5 [Month 4] (N=49,48)	7.75 (6.05 to 9.92)	7.87 (6.02 to 10.29)
Anti-6B [Month 0] (N=49,46)	0.03 (0.02 to 0.03)	0.03 (0.02 to 0.03)
Anti-6B [Month 2] (N=49,49)	1.61 (1.03 to 2.52)	1.48 (1.02 to 2.13)
Anti-6B [Month 3] (N=50,49)	1.51 (1.06 to 2.15)	1.35 (0.98 to 1.87)
Anti-6B [Month 4] (N=49,48)	3.12 (2.1 to 4.64)	2.93 (2.17 to 3.95)
Anti-7F [Month 0] (N=50,50)	0.04 (0.03 to 0.05)	0.04 (0.03 to 0.05)
Anti-7F [Month 2] (N=49,49)	8.51 (6.94 to 10.42)	6.67 (5.44 to 8.19)
Anti-7F [Month 3] (N=50,49)	5.46 (4.37 to 6.83)	4.68 (3.76 to 5.81)
Anti-7F [Month 4] (N=48,48)	11.08 (8.9 to 13.81)	10.29 (7.92 to 13.37)
Anti-9V [Month 0] (N=49,48)	0.04 (0.03 to 0.05)	0.04 (0.03 to 0.05)
Anti-9V [Month 2] (N=49,49)	2.55 (1.86 to 3.49)	1.67 (1.21 to 2.29)
Anti-9V [Month 3] (N=50,49)	1.9 (1.42 to 2.56)	1.52 (1.16 to 2)
Anti-9V [Month 4] (N=49,48)	4.73 (3.4 to 6.58)	3.76 (2.67 to 5.3)
Anti-14 [Month 0] (N=47,48)	0.08 (0.06 to 0.12)	0.07 (0.05 to 0.1)
Anti-14 [Month 2] (N=50,46)	4.91 (3.48 to 6.95)	4.81 (3.67 to 6.29)
Anti-14 [Month 3] (N=50,49)	4.71 (3.45 to 6.43)	4.98 (4.01 to 6.2)
Anti-14 [Month 4] (N=49,48)	10.24 (7.96 to 13.18)	10.69 (8.34 to 13.71)
Anti-18C [Month 0] (N=50,49)	0.03 (0.03 to 0.03)	0.03 (0.03 to 0.04)
Anti-18C [Month 2] (N=49,47)	12.92 (9.93 to 16.82)	14.62 (11.61 to 18.4)
Anti-18C [Month 3] (N=50,49)	8.43 (6.53 to 10.88)	11.49 (9.24 to 14.29)
Anti-18C [Month 4] (N=49,48)	23.57 (18.38 to 30.22)	31.88 (25.34 to 40.11)
Anti-19F [Month 0] (N=49,48)	0.05 (0.04 to 0.06)	0.04 (0.04 to 0.06)
Anti-19F [Month 2] (N=50,49)	11.13 (7.97 to 15.54)	9.77 (6.16 to 15.48)
Anti-19F [Month 3] (N=50,49)	6.54 (4.79 to 8.92)	7.39 (5.04 to 10.81)
Anti-19F [Month 4] (N=49,48)	15.59 (11.24 to 21.62)	15.85 (10.52 to 23.89)
Anti-23F [Month 0] (N=48,48)	0.03 (0.03 to 0.04)	0.04 (0.03 to 0.05)
Anti-23F [Month 2] (N=50,48)	1.29 (0.79 to 2.1)	0.93 (0.6 to 1.45)
Anti-23F [Month 3] (N=50,48)	1 (0.65 to 1.56)	1.08 (0.74 to 1.56)
Anti-23F [Month 4] (N=49,48)	3.11 (1.85 to 5.24)	3.17 (2.04 to 4.91)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 7-11S and 7-11NS groups.

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End point title

Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 7-11S and 7-11NS groups. ^[17]

End point description

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 2), prior to (Month 3) and one month after booster vaccination (Month 4)

Notes
[17] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	50	49
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A [Month 0] (N=47,44)	0.03 (0.03 to 0.04)	0.03 (0.03 to 0.04)
Anti-6A [Month 2] (N=48,46)	0.18 (0.11 to 0.3)	0.16 (0.11 to 0.24)
Anti-6A [Month3] (N=50,47)	0.23 (0.14 to 0.37)	0.22 (0.16 to 0.32)
Anti-6A [Month 4] (N=48,48)	0.44 (0.28 to 0.7)	0.43 (0.3 to 0.62)
Anti-19A [Month 0] (N=48,49)	0.04 (0.03 to 0.06)	0.06 (0.04 to 0.1)
Anti-19A [Month 2] (N=50,49	0.46 (0.28 to 0.76)	0.77 (0.5 to 1.18)
Anti-19A [Month3] (N=50,48)	0.44 (0.27 to 0.7)	0.77 (0.51 to 1.17)
Anti-19A [Month 4] (N=49,48)	1.49 (0.93 to 2.38)	2.35 (1.5 to 3.67)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 12-23S and 12-23NS group.

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End point title

Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 12-23S and 12-23NS group. ^[18]

End point description

End point type

Secondary

End point timeframe

Prior to (Month 0), one month after first dose vaccination (Month 2) and one month after second dose vaccination (Month 3)

Notes
[18] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	48	47
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-1 [Month 0] (N=47,45)	0.04 (0.03 to 0.05)	0.04 (0.03 to 0.05)
Anti-1 [Month 2] (N=48,47)	1.39 (1.07 to 1.8)	1.49 (1.18 to 1.89)
Anti-1 [Month 3] (N=48,46)	4.67 (3.75 to 5.81)	4.26 (3.38 to 5.37)
Anti-4 [Month 0] (N=48,47)	0.04 (0.03 to 0.05)	0.04 (0.03 to 0.05)
Anti-4 [Month 2] (N=47,47)	4.22 (3.23 to 5.51)	3.74 (2.96 to 4.72)
Anti-4 [Month 3] (N=47,46)	8.87 (7.03 to 11.19)	7.02 (5.85 to 8.43)
Anti-5 [Month 0] (N=48,47)	0.06 (0.04 to 0.08)	0.08 (0.06 to 0.11)
Anti-5 [Month 2] (N=48,47)	1.06 (0.77 to 1.47)	1.1 (0.83 to 1.44)
Anti-5 [Month 3] (N=48,46)	5.52 (4.23 to 7.2)	4.07 (3.06 to 5.42)
Anti-6B [Month 0] (N=48,47)	0.03 (0.03 to 0.04)	0.04 (0.03 to 0.05)
Anti-6B [Month 2] (N=48,47)	0.41 (0.28 to 0.62)	0.34 (0.24 to 0.48)
Anti-6B [Month 3] (N=48,46)	1.37 (0.91 to 2.07)	1.25 (0.87 to 1.79)
Anti-7F [Month 0] (N=48,47)	0.07 (0.05 to 0.11)	0.05 (0.04 to 0.07)
Anti-7F [Month 2] (N=48,47)	2.74 (2.13 to 3.52)	3.17 (2.56 to 3.93)
Anti-7F [Month 3] (N=48,46)	6.81 (5.32 to 8.7)	6.36 (5.25 to 7.69)
Anti-9V [Month 0] (N=48,47)	0.08 (0.05 to 0.12)	0.05 (0.04 to 0.07)
Anti-9V [Month 2] (N=48,47)	0.99 (0.72 to 1.34)	0.83 (0.62 to 1.11)
Anti-9V [Month 3] (N=48,46)	2.35 (1.85 to 3)	1.72 (1.31 to 2.25)
Anti-14 [Month 0] (N=47,46)	0.11 (0.07 to 0.16)	0.09 (0.06 to 0.12)
Anti-14 [Month 2] (N=48,47)	1.87 (1.46 to 2.4)	1.24 (0.92 to 1.66)
Anti-14 [Month 3] (N=47,45)	7.59 (5.84 to 9.87)	5.75 (4.33 to 7.62)
Anti-18C [Month 0] (N=48,47)	0.04 (0.03 to 0.06)	0.05 (0.04 to 0.07)
Anti-18C [Month 2] (N=48,47)	6.21 (4.77 to 8.1)	6.12 (4.56 to 8.21)
Anti-18C [Month 3] (N=47,45)	25.52 (20.66 to 31.53)	22.64 (18.14 to 28.26)
Anti-19F [Month 0] (N=48,47)	0.06 (0.04 to 0.09)	0.08 (0.05 to 0.12)
Anti-19F [Month 2] (N=48,47)	5.88 (4.44 to 7.8)	5.12 (3.79 to 6.94)
Anti-19F [Month 3] (N=48,46)	18 (13.97 to 23.2)	14.46 (10.81 to 19.34)
Anti-23F [Month 0] (N=48,47)	0.03 (0.03 to 0.04)	0.05 (0.03 to 0.07)
Anti-23F [Month 2] (N=48,47)	0.5 (0.32 to 0.77)	0.35 (0.25 to 0.49)
Anti-23F [Month 3] (N=47,46)	1.95 (1.32 to 2.87)	1.4 (1.05 to 1.87)

No statistical analyses for this end point

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 12-23S and 12-23NS groups.

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End point title

Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 12-23S and 12-23NS groups. ^[19]

End point description

End point type

Secondary

End point timeframe

Prior to (Month 0), one month after first dose vaccination (Month 2) and one month after second dose vaccination (Month 3)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	48	47
Units: µg/mL
geometric mean (confidence interval 95%)
Anti-6A [Month 0] (N=45,44)	0.03 (0.03 to 0.03)	0.04 (0.03 to 0.05)
Anti-6A [Month 2] (N=47,47)	0.15 (0.1 to 0.23)	0.12 (0.08 to 0.18)
Anti-6A [Month 3] (N=47,46)	0.39 (0.23 to 0.66)	0.31 (0.2 to 0.48)
Anti-19A [Month 0] (N=47,45)	0.06 (0.04 to 0.09)	0.07 (0.04 to 0.11)
Anti-19A [Month 2] (N=48,47)	0.77 (0.5 to 1.17)	0.75 (0.47 to 1.19)
Anti-19A [Month 3] (N=48,46)	3.15 (2.13 to 4.65)	2.79 (1.93 to 4.05)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes - <6S and <6NS groups.

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End point title

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes - <6S and <6NS groups. ^[20]

End point description

Pneumococcal vaccine serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation.

End point type

Secondary

End point timeframe

One month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

Notes
[20] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	46	41
Units: Titer
geometric mean (confidence interval 95%)
Opsono-1 Month 3 (N=45,41)	106.4 (56 to 202.2)	94.6 (49.9 to 179.5)
Opsono-1 Month 8 (N=41,33)	11.7 (6.8 to 20.1)	10.9 (6 to 20.1)
Opsono-1 Month 9 (N=41,35)	930.5 (606.3 to 1427.9)	750.4 (401.4 to 1403)
Opsono-4 Month 3 (N=44,38)	1316.6 (1014 to 1709.7)	992.5 (680 to 1448.4)
Opsono-4 Month 8 (N=40,31)	222.1 (130.6 to 377.8)	108.3 (51.6 to 227.6)
Opsono-4 Month 9 (N=41,33)	2064.2 (1625.3 to 2621.8)	2079.3 (1425.7 to 3032.7)
Opsono-5 Month 3 (N=44,41)	106.9 (66.8 to 171.2)	119.4 (81.4 to 175.2)
Opsono-5 Month 8 (N=40,33)	14.9 (8.9 to 24.9)	15.8 (9.6 to 26.1)
Opsono-5 Month 9 (N=41,33)	273.2 (200.6 to 372)	277.5 (168.8 to 456.1)
Opsono-6B Month 3 (N=41,37)	1043.3 (605.3 to 1798.3)	446.2 (207.4 to 960)
Opsono-6B Month 8 (N=39,32)	285.3 (150.1 to 542.1)	245.6 (115 to 524.3)
Opsono-6B Month 9 (N=40,33)	952.2 (638.8 to 1419.3)	989.2 (530.6 to 1843.9)
Opsono-7F Month 3 (N=42,37)	4644.1 (3519.3 to 6128.4)	4924.2 (3430.2 to 7068.8)
Opsono-7F Month 8 (N=40,32)	1747.2 (1225.4 to 2491.3)	1585.7 (1133.8 to 2217.8)
Opsono-7F Month 9 (N=39,32)	7262.9 (5257.6 to 10033.1)	8120.3 (5802.1 to 11364.8)
Opsono-9V Month 3 (N=46,39)	1438.6 (1084 to 1909.3)	1116.8 (679.6 to 1835.2)
Opsono-9V Month 8 (N=38,32)	215.5 (97.5 to 476.1)	244.5 (123.9 to 482.2)
Opsono-9V Month 9 (N=40,32)	2062.3 (1569 to 2710.8)	2987.2 (2149.4 to 4151.6)
Opsono-14 Month 3 (N=44,41)	1689.9 (1090.7 to 2618.2)	1062.3 (562.8 to 2005.2)
Opsono-14 Month 8 (N=39,26)	215.9 (113.6 to 410.1)	132.5 (60.3 to 291.5)
Opsono-14 Month 9 (N=40,33)	1571.5 (1114.2 to 2216.4)	1454.1 (741.8 to 2850.5)
Opsono-18C Month 3 (N=40,37)	873.8 (591.7 to 1290.4)	524.7 (319.6 to 861.6)
Opsono-18C Month 8 (N=39,30)	46.5 (28.5 to 75.7)	28.7 (17.5 to 47.3)
Opsono-18C Month 9 (N=39,31)	1246 (776.7 to 1999)	1011.8 (686.4 to 1491.4)
Opsono-19F Month 3 (N=43,39)	558.9 (376.3 to 830.2)	266.1 (148.2 to 477.8)
Opsono-19F Month 8 (N=41,32)	60.7 (37.1 to 99.3)	43.4 (22.6 to 83.2)
Opsono-19F Month 9 (N=40,33)	652.9 (413.3 to 1031.5)	486.7 (278.9 to 849.4)
Opsono-23F Month 3 (N=44,37)	705.1 (309.2 to 1607.8)	759.7 (326.7 to 1766.6)
Opsono-23F Month 8 (N=36,31)	85.2 (27.5 to 264.4)	41.6 (14.6 to 118.9)
Opsono-23F Month 9 (N=39,33)	4231.2 (2793.7 to 6408.3)	1454 (736.1 to 2872.3)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- <6S and <6NS groups

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End point title

Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- <6S and <6NS groups ^[21]

End point description

Cross-reactive Pneumococcal vaccine serotypes assessed were 6A and 19A and were calculated, expressed as geometric mean titers (GMTs). The seropositivity cut-off for the assay was ≥ 8. Antibody titers < 8 were given an arbitrary value of half the cut-off for the purpose of GMT calculation

End point type

Secondary

End point timeframe

One month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

Notes
[21] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	42	41
Units: Titers
geometric mean (confidence interval 95%)
Opsono-6A [Month 3] (N=42,41)	24.73 (11.46 to 53.37)	9.45 (5.32 to 16.75)
Opsono-6A [Month 8] (N=40,33)	18.23 (8.97 to 37.09)	17.59 (8.08 to 38.3)
Opsono-6A [Month 9] (N=38,32)	35.35 (15.6 to 80.12)	30.7 (12.14 to 77.64)
Opsono-19A [Month 3] (N=38,34)	9.42 (5.65 to 15.7)	5.04 (3.83 to 6.63)
Opsono-19A [Month 8] (N=34,23)	6.31 (4.28 to 9.32)	5.83 (3.95 to 8.61)
Opsono-19A [Month 9] (N=26,28)	22.06 (9.49 to 51.3)	19.44 (10.25 to 36.86)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 7-11S and 7-11NS groups.

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End point title

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 7-11S and 7-11NS groups. ^[22]

End point description

End point type

Secondary

End point timeframe

One month after primary vaccination (Month 2), prior to (Month 3) and one month after booster vaccination (Month 4)

Notes
[22] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	49	46
Units: Titer
geometric mean (confidence interval 95%)
Opsono-1 Month 2 (N=48,45)	134.7 (83.6 to 216.9)	88.1 (53.7 to 144.6)
Opsono-1 Month 3 (N=48,46)	74.2 (42.6 to 129.3)	48 (26.6 to 86.7)
Opsono-1 Month 4 (N=48,44)	516 (307.6 to 865.7)	511.3 (293.2 to 891.8)
Opsono-4 Month 2 (N=49,44)	1636.3 (1217.5 to 2199.2)	1771.1 (1359 to 2308.2)
Opsono-4 Month 3 (N=45,45)	812.7 (584.5 to 1130.1)	1048.3 (790.4 to 1390.3)
Opsono-4 Month 4 (N=48,43)	2130.5 (1639.1 to 2769.2)	2415.5 (1686.5 to 3459.8)
Opsono-5 Month 2 (N=49,46)	105.7 (67.7 to 165.1)	85.8 (59.4 to 124)
Opsono-5 Month 3 (N=47,47)	54.1 (34.9 to 83.6)	49.2 (31.7 to 76.3)
Opsono-5 Month 4 (N=48,43)	277.4 (180.7 to 425.7)	289.6 (190.9 to 439.3)
Opsono-6B Month 2 (N=48,43)	702.5 (413.2 to 1194.2)	696.6 (388.5 to 1249.2)
Opsono-6B Month 3 (N=44,45)	708.3 (422.9 to 1186.1)	615.5 (337.3 to 1123.1)
Opsono-6B Month 4 (N=46,43)	1360 (860.2 to 2150.3)	1305.4 (731.9 to 2328.4)
Opsono-7F Month 2 (N=47,40)	6694.3 (5055.1 to 8864.9)	10452 (7782.7 to 14036.6)
Opsono-7F Month 3 (N=46,46)	7776.9 (6000.8 to 10078.7)	9336.3 (6752.4 to 12908.9)
Opsono-7F Month 4 (N=47,39)	10854.8 (9051.6 to 13017.2)	9362.8 (6882.3 to 12737.3)
Opsono-9V Month 2 (N=48,42)	2858.2 (1875.3 to 4356.2)	2667.9 (1677.9 to 4242)
Opsono-9V Month 3 (N=44,46)	1982.9 (1192.1 to 3298.2)	1986.2 (1167.8 to 3378.2)
Opsono-9V Month 4 (N=48,41)	3047.9 (2389.7 to 3887.3)	2719.2 (1681 to 4398.9)
Opsono-14 Month 2 (N=44,43)	2109.5 (1299 to 3425.9)	4009.9 (2501.9 to 6426.7)
Opsono-14 Month 3 (N=46,46)	1431.6 (865.2 to 2368.6)	2128.3 (1477.5 to 3065.9)
Opsono-14 Month 4 (N=46,40)	3414.9 (2237.4 to 5211.9)	3717.3 (2403.9 to 5748.5)
Opsono-18C Month 2 (N=39,37)	744.4 (393.3 to 1409.2)	1605.6 (937.1 to 2751.1)
Opsono-18C Month 3 (N=40,42)	411.4 (214.4 to 789.7)	746.4 (430.5 to 1294.1)
Opsono-18C Month 4 (N=44,40)	2218.9 (1577.5 to 3121.2)	3238.7 (1874.7 to 5595)
Opsono-19F Month 2 (N=47,43)	393.4 (214.4 to 722)	491.5 (256.8 to 940.6)
Opsono-19F Month 3 (N=45,46)	160.2 (86.8 to 295.6)	279.5 (161.1 to 484.9)
Opsono-19F Month 4 (N=47,41)	1347.7 (813.6 to 2232.3)	1174.4 (605.6 to 2277.3)
Opsono-23F Month 2 (N=46,44)	1545.1 (788.3 to 3028.2)	2107.5 (1155 to 3845.5)
Opsono-23F Month 3 (N=40,46)	1168.8 (560.8 to 2435.8)	1026.2 (458.3 to 2298)
Opsono-23F Month 4 (N=47,43)	2038.8 (977.1 to 4254.4)	3525.1 (1974.2 to 6294.4)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 7-11S and 7-11NS groups

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End point title

Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 7-11S and 7-11NS groups ^[23]

End point description

End point type

Secondary

End point timeframe

One month after primary vaccination (Month 2), prior to (Month 3) and one month after booster vaccination (Month 4)

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	49	45
Units: Titers
geometric mean (confidence interval 95%)
Opsono-6A [Month 2] (N=49,39)	40.59 (19.11 to 86.23)	51.23 (22.85 to 114.88)
Opsono-6A [Month 3] (N=44,45)	38.11 (17.04 to 85.21)	36.27 (16.89 to 77.89)
Opsono-6A [Month 4] (N=45,43)	77.09 (35.58 to 167.04)	98.18 (43.05 to 223.96)
Opsono-19A [Month 2] (N=40,31)	15.21 (7.95 to 29.08)	108.31 (49.55 to 236.78)
Opsono-19A [Month 3] (N=37,26)	14.65 (7.71 to 27.81)	19.4 (8.04 to 46.82)
Opsono-19A [Month 4] (N=31,29)	76.09 (30.5 to 189.83)	449.06 (170.05 to 1185.87)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 12-23S and 12-23NS groups.

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End point title

Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 12-23S and 12-23NS groups. ^[24]

End point description

End point type

Secondary

End point timeframe

One month after first dose vaccination (Month 2) and one month after second dose vaccination (Month 3)

Notes
[24] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	46	45
Units: Titer
geometric mean (confidence interval 95%)
Opsono-1 Month 2 (N=46,45)	9.3 (6.1 to 14.3)	10.9 (6.8 to 17.4)
Opsono-1 Month 3 (N=45,43)	195.7 (119.9 to 319.3)	115.1 (64 to 206.8)
Opsono-4 Month 2 (N=44,43)	1086.3 (758.4 to 1555.9)	1539.4 (1128.4 to 2100.1)
Opsono-4 Month 3 (N=44,43)	2089.7 (1635 to 2670.8)	3193.9 (2241.3 to 4551.4)
Opsono-5 Month 2 (N=45,45)	9.8 (7.1 to 13.7)	9.6 (6.6 to 13.7)
Opsono-5 Month 3 (N=44,44)	151.3 (99.8 to 229.2)	84 (53.5 to 131.8)
Opsono-6B Month 2 (N=41,42)	345.1 (172.4 to 690.7)	278.4 (131.8 to 588.4)
Opsono-6B Month 3 (N=43,43)	748.4 (425.9 to 1315)	866.4 (511.8 to 1466.7)
Opsono-7F Month 2 (N=44,45)	5462.3 (4108.9 to 7261.4)	5802.2 (4678.6 to 7195.6)
Opsono-7F Month 3 (N=44,42)	10279.4 (7836.7 to 13483.6)	10131.4 (8303.7 to 12361.6)
Opsono-9V Month 2 (N=43,44)	1976.2 (1392.6 to 2804.4)	2359 (1514.3 to 3674.9)
Opsono-9V Month 3 (N=44,43)	3778.2 (2880 to 4956.4)	4276.8 (3122.3 to 5858.3)
Opsono-14 Month 2 (N=42,40)	711.2 (400.7 to 1262.4)	865.6 (583.2 to 1284.9)
Opsono-14 Month 3 (N=45,40)	2704.5 (1856.4 to 3940)	2737.5 (1890 to 3965.1)
Opsono-18C Month 2 (N=32,34)	1035.5 (507.6 to 2112.5)	449.2 (222.8 to 905.9)
Opsono-18C Month 3 (N=40,40)	2873.1 (2070 to 3987.6)	2126.8 (1509.7 to 2996.3)
Opsono-19F Month 2 (N=44,43)	229.1 (132.9 to 395)	248 (143 to 430.1)
Opsono-19F Month 3 (N=45,43)	1845.3 (1169.3 to 2912.1)	1271.4 (825.4 to 1958.3)
Opsono-23F Month 2 (N=44,44)	2572.2 (1264.1 to 5233.9)	2433.6 (1309.7 to 4522)
Opsono-23F Month 3 (N=42,41)	5016.6 (3176.6 to 7922.4)	5325.4 (2857.8 to 9923.9)

No statistical analyses for this end point

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 12-23S and 12-23NS groups

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End point title

Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 12-23S and 12-23NS groups ^[25]

End point description

End point type

Secondary

End point timeframe

One month after first dose vaccination (Month 2) and one month after second dose vaccination (Month 3)

Notes
[25] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	44	42
Units: Titers
geometric mean (confidence interval 95%)
Opsono-6A [Month 2] (N=44,42)	82.82 (40.27 to 170.33)	77.25 (31.81 to 187.64)
Opsono-6A [Month 3] (N=40,39)	147.91 (63.11 to 346.68)	157.37 (59.23 to 418.11)
Opsono-19A [Month 2] (N=23,27)	28.37 (11.84 to 67.98)	25.68 (11.6 to 56.84)
Opsono-19A [Month 3] (N=19,23)	214.17 (75.58 to 606.93)	321.14 (144.75 to 712.5)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Protein D (PD) – 7-11S and 7-11NS groups.

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End point title

Concentrations of Antibodies against Protein D (PD) – 7-11S and 7-11NS groups. ^[26]

End point description

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 2), prior to (Month 3) and one month after booster vaccination (Month 4)

Notes
[26] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	7-11S Group	7-11NS Group
Number of subjects analysed	50	50
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD [Month 0] (N=47,48)	72.73 (57.23 to 92.42)	88.74 (70.85 to 111.13)
Anti-PD [Month 2] (N=50,50)	1313.39 (1014.3 to 1700.67)	1489.78 (1171.98 to 1893.76)
Anti-PD [Month 3] (N=50,49)	932.52 (732.63 to 1186.96)	1063.54 (844.52 to 1339.37)
Anti-PD [Month 4] (N=49,48)	2695.5 (2150.74 to 3378.24)	2638.27 (2049.91 to 3395.49)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Protein D (PD) – 12-23S and 12-23NS groups.

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End point title

Concentrations of Antibodies against Protein D (PD) – 12-23S and 12-23NS groups. ^[27]

End point description

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after first dose vaccination (Month 2) and one month after second dose vaccination (Month 3)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Results are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	12-23S Group	12-23NS Group
Number of subjects analysed	48	47
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-PD [Month 0] (N=47,46)	79.59 (62.08 to 102.04)	76.22 (61.39 to 94.63)
Anti-PD [Month 2] (N=48,47)	199.23 (150.51 to 263.72)	184.34 (140.21 to 242.35)
Anti-PD [Month 3] (N=48,46)	1376.56 (1020.71 to 1856.46)	760.99 (553.23 to 1046.77)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT) - <6S and <6NS groups

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End point title

Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT) - <6S and <6NS groups ^[28]

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as International units per millilitre (IU/mL). Seroprotection status, defined as Anti-DT or Anti-TT antibody concentration equal to or greater than 0.1 IU/mL.

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

Notes
[28] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	48	46
Units: IU/mL
geometric mean (confidence interval 95%)
Anti-DT Month 0 (N=48,45)	0.07 (0.05 to 0.08)	0.06 (0.05 to 0.07)
Anti-DT Month 3 (N=48,46)	3.22 (2.59 to 4)	3.5 (2.82 to 4.34)
Anti-DT Month 8 (N=44,37)	0.62 (0.5 to 0.77)	0.9 (0.72 to 1.12)
Anti-DT Month 9 (N=44,38)	6.58 (5.44 to 7.97)	7.55 (6.11 to 9.32)
Anti-TT Month 0 (N=48,46)	1.54 (1.13 to 2.09)	1.22 (0.85 to 1.76)
Anti-TT Month 3 (N=48,46)	4.04 (3.26 to 5.01)	4.13 (3.27 to 5.22)
Anti-TT Month 8 (N=44,38)	1.19 (0.96 to 1.48)	1.33 (1.08 to 1.63)
Anti-TT Month 9 (N=44,38)	10.88 (9.24 to 12.81)	11.11 (9.62 to 12.83)

No statistical analyses for this end point

Secondary: Concentrations of Antibodies against Bordetella Pertussis (BPT) - <6S and <6NS groups

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End point title

Concentrations of Antibodies against Bordetella Pertussis (BPT) - <6S and <6NS groups ^[29]

End point description

Concentrations of antibodies are presented as geometric mean concentrations expressed as Enzyme-Linked Immuno-Sorbent Assay (ELISA) units per millilitre (EL.U/mL). Seropositivity was defined as an antibody concentration equal to or greater than 15 EL.U/mL

End point type

Secondary

End point timeframe

Prior to (Month 0) and one month after primary vaccination (Month 3), prior to (Month 8) and one month after booster vaccination (Month 9)

Notes
[29] - 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 are provided only for 2 groups as timeframe has been defined specifically for those 2 groups.

End point values	<6S Group	<6NS Group
Number of subjects analysed	48	46
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-BPT Month 0 (N=48,46)	7.71 (7.29 to 8.16)	7.77 (7.39 to 8.17)
Anti-BPT Month 3 (N=48,46)	105.61 (86.93 to 128.3)	101.74 (84.56 to 122.42)
Anti-BPT Month 8 (N=44,38)	22.67 (17.45 to 29.45)	22.69 (17.88 to 28.8)
Anti-BPT Month 9 (N=44,38)	177.87 (152.1 to 207.99)	190.58 (167.67 to 216.63)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms: within 4 days after each vaccination dose. Unsolicited symptoms: within 31 days after each vaccination. SAEs: during the whole study period.

Adverse event reporting additional description

The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

14.0

Reporting group title

<6S Group

Reporting group description

Reporting group title

<6NS Group

Reporting group description

Reporting group title

7-11S Group

Reporting group description

Reporting group title

7-11NS Group

Reporting group description

Reporting group title

12-23S Group

Reporting group description

Children between 12-23 months of age with sickle cell disease, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Reporting group title

12-23NS Group

Reporting group description

Healthy children between 12-23 months of age, receiving a 2-dose vaccination with 10Pn-PD-DiT vaccine starting at 12-23 months of age with an interval of 2 to 4 months between doses.

Serious adverse events	<6S Group	<6NS Group	7-11S Group	7-11NS Group	12-23S Group	12-23NS Group
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 50 (6.00%)	9 / 50 (18.00%)	3 / 50 (6.00%)	4 / 50 (8.00%)	2 / 50 (4.00%)	2 / 50 (4.00%)
number of deaths (all causes)	1	1	1	0	0	0
number of deaths resulting from adverse events
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Enteritis
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 50 (2.00%)	6 / 50 (12.00%)	1 / 50 (2.00%)	2 / 50 (4.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 1	0 / 6	0 / 1	0 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malaria
subjects affected / exposed	3 / 50 (6.00%)	3 / 50 (6.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	1 / 50 (2.00%)	2 / 50 (4.00%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 50 (2.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (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
Meningitis Salmonella
subjects affected / exposed	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis acute
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (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
Metabolism and nutrition disorders
Malnutrition
subjects affected / exposed	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	<6S Group	<6NS Group	7-11S Group	7-11NS Group	12-23S Group	12-23NS Group
Total subjects affected by non serious adverse events
subjects affected / exposed	48 / 50 (96.00%)	43 / 50 (86.00%)	31 / 50 (62.00%)	29 / 50 (58.00%)	29 / 50 (58.00%)	20 / 50 (40.00%)
General disorders and administration site conditions
Pain (Primary vaccination)
alternative assessment type: Systematic
subjects affected / exposed	17 / 50 (34.00%)	23 / 50 (46.00%)	12 / 50 (24.00%)	15 / 50 (30.00%)	13 / 50 (26.00%)	9 / 50 (18.00%)
occurrences all number	17	23	12	15	13	9
Pain (Booster vaccination)
Additional description: Groups 12-23S and 12-23NS were not included in the analysis since they received no booster dose, so the numbers presented for them are placeholder values.
alternative assessment type: Systematic
subjects affected / exposed ^[1]	11 / 49 (22.45%)	6 / 49 (12.24%)	3 / 50 (6.00%)	0 / 50 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	11	6	3	0	0	0
Irritability (Primary vaccination)
alternative assessment type: Systematic
subjects affected / exposed	3 / 50 (6.00%)	6 / 50 (12.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	2 / 50 (4.00%)	0 / 50 (0.00%)
occurrences all number	3	6	0	0	2	0
Irritability (Booster vaccination)
Additional description: Groups 12-23S and 12-23NS were not included in the analysis since they received no booster dose, so the numbers presented for them are placeholder values.
alternative assessment type: Systematic
subjects affected / exposed ^[2]	6 / 49 (12.24%)	0 / 49 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	6	0	0	0	0	0
Fever (Primary vaccination)
Additional description: Fever was assessed rectally.
alternative assessment type: Systematic
subjects affected / exposed	48 / 50 (96.00%)	43 / 50 (86.00%)	31 / 50 (62.00%)	29 / 50 (58.00%)	29 / 50 (58.00%)	20 / 50 (40.00%)
occurrences all number	48	43	31	39	29	20
Fever (Booster vaccination)
Additional description: Fever was assessed rectally. Groups 12-23S and 12-23NS were not included in the analysis since they received no booster dose, so the numbers presented for them are placeholder values.
alternative assessment type: Systematic
subjects affected / exposed ^[3]	38 / 49 (77.55%)	31 / 49 (63.27%)	14 / 50 (28.00%)	13 / 50 (26.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	38	31	14	13	0	0
Pyrexia
subjects affected / exposed	1 / 50 (2.00%)	1 / 50 (2.00%)	3 / 50 (6.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	1	3	1	0	1
Blood and lymphatic system disorders
Sickle cell anaemia with crisis
subjects affected / exposed	0 / 50 (0.00%)	0 / 50 (0.00%)	3 / 50 (6.00%)	0 / 50 (0.00%)	10 / 50 (20.00%)	0 / 50 (0.00%)
occurrences all number	0	0	3	0	10	0
Gastrointestinal disorders
Diarrhoea (Primary)
subjects affected / exposed	7 / 50 (14.00%)	4 / 50 (8.00%)	1 / 50 (2.00%)	3 / 50 (6.00%)	1 / 50 (2.00%)	1 / 50 (2.00%)
occurrences all number	7	4	1	3	1	1
Enteritis (Primary)
subjects affected / exposed	2 / 50 (4.00%)	3 / 50 (6.00%)	6 / 50 (12.00%)	2 / 50 (4.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences all number	2	3	6	2	0	1
Enteritis (Booster)
Additional description: Groups 12-23S and 12-23NS were not included in the analysis since they received no booster dose, so the numbers presented for them are placeholder values.
subjects affected / exposed ^[4]	0 / 49 (0.00%)	2 / 49 (4.08%)	0 / 50 (0.00%)	3 / 50 (6.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	2	0	3	0	0
Diarrhoea (Booster)
subjects affected / exposed ^[5]	1 / 49 (2.04%)	2 / 49 (4.08%)	3 / 50 (6.00%)	1 / 50 (2.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	2	3	1	0	0
Abdominal pain
subjects affected / exposed	3 / 50 (6.00%)	1 / 50 (2.00%)	2 / 50 (4.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)
occurrences all number	3	1	2	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	4 / 50 (8.00%)	5 / 50 (10.00%)	1 / 50 (2.00%)	1 / 50 (2.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)
occurrences all number	4	5	1	1	1	0
Infections and infestations
Malaria (Primary)
subjects affected / exposed	10 / 50 (20.00%)	7 / 50 (14.00%)	9 / 50 (18.00%)	13 / 50 (26.00%)	10 / 50 (20.00%)	10 / 50 (20.00%)
occurrences all number	10	7	9	13	10	10
Malaria (Booster)
Additional description: Groups 12-23S and 12-23NS were not included in the analysis since they received no booster dose, so the numbers presented for them are placeholder values.
subjects affected / exposed ^[6]	0 / 49 (0.00%)	8 / 49 (16.33%)	8 / 50 (16.00%)	4 / 50 (8.00%)	0 / 1 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	8	8	4	0	0
Bronchitis
subjects affected / exposed	9 / 50 (18.00%)	10 / 50 (20.00%)	3 / 50 (6.00%)	8 / 50 (16.00%)	1 / 50 (2.00%)	4 / 50 (8.00%)
occurrences all number	9	10	3	8	1	4
Gastroenteritis
subjects affected / exposed	6 / 50 (12.00%)	5 / 50 (10.00%)	3 / 50 (6.00%)	9 / 50 (18.00%)	1 / 50 (2.00%)	6 / 50 (12.00%)
occurrences all number	6	5	3	9	1	6
Rhinitis
subjects affected / exposed	4 / 50 (8.00%)	7 / 50 (14.00%)	4 / 50 (8.00%)	3 / 50 (6.00%)	3 / 50 (6.00%)	4 / 50 (8.00%)
occurrences all number	4	7	4	3	3	4
Nasopharyngitis
subjects affected / exposed	6 / 50 (12.00%)	4 / 50 (8.00%)	2 / 50 (4.00%)	7 / 50 (14.00%)	3 / 50 (6.00%)	5 / 50 (10.00%)
occurrences all number	6	4	2	7	3	5
Gastrointestinal fungal infection
subjects affected / exposed	4 / 50 (8.00%)	5 / 50 (10.00%)	3 / 50 (6.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	0 / 50 (0.00%)
occurrences all number	4	5	3	1	0	0
Conjunctivitis
subjects affected / exposed	2 / 50 (4.00%)	3 / 50 (6.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	2 / 50 (4.00%)	0 / 50 (0.00%)
occurrences all number	2	3	0	1	2	0
Ear infection
subjects affected / exposed	3 / 50 (6.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences all number	3	1	0	1	0	1

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis of the non-serious adverse event included only subjects with documented data.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis of the non-serious adverse event included only subjects with documented data.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis of the non-serious adverse event included only subjects with documented data.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis of the non-serious adverse event included only subjects with documented data.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis of the non-serious adverse event included only subjects with documented data.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis of the non-serious adverse event included only subjects with documented data.

More information

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Were there any global substantial amendments to the protocol? Yes

15 Apr 2010

The oral polio vaccine was to be provided in multidose vials Changes in the randomization of treatment Inconsistencies regarding the age for booster vaccination in the 7-11 month groups Changes in the priority ranking of immunological assays Changes in the definition of the Epochs Update of Rationale of the study

03 Sep 2010

•For clarification, the inclusion criteria for children with sickle cell disease have been further detailed. •An additional blood sample for SCD testing was planned to be taken at the pre-vaccination timepoint from subjects aged 7-11 and 12-23 months without hemoglobin status confirmed by electrophoresis available. •Presentation of oral polio vaccine that was to be used has changed: 10- or 20-dose vials were used. In addition, the use of one 10- or 20-dose vial to vaccinate up to 10 or 20 subjects, respectively, on the same day was allowed. •The immunogenicity objectives related to the co-administered OPV have been removed since there are no plans to test poliovirus immune response. •The contact details for the emergency code break have been clarified.

08 May 2012

The main changes and their rationale are the following: •Additional information was given about administration of vaccines through the local EPI program. •Extension of the recruitment period due to a lower enrolment rate than expected. •Additional exclusion criterion for children of the <6S and <6NS groups to clarify differences between groups with regard to administration of vaccines included in the EPI program either as study vaccines or outside the study. •Additional exclusion criterion for all groups, i.e. exclusion of subjects being heterozygous or carriers of abnormal haemoglobin (e.g. haemoglobin S, haemoglobin C) who are not considered to have SCD, to avoid potential bias and to keep homogeneity of the examined groups.

09 Apr 2013

In the past few months, GSK Biologicals has been investigating the quality of some serology assays used in clinical studies, including the Streptococcus pneumonia opsonophagocytic activity (OPA) assay used in the present trial. This protocol amendment reflected the fact that delays in the availability of the assay results would lead to changes in the analysis plan. Therefore, the sequence of analysis has been modified to perform study analysis in one final step on all immunogenicity and safety data obtained up to one month after administration of the last dose of study vaccine for all study groups. The results of this final analysis were presented in a final clinical study report.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - <6S and <6NS groups.

Primary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - <6S and <6NS groups.

Primary: Concentrations of Antibodies against Protein D (PD) - <6S and <6NS groups.

Primary: Concentrations of Antibodies against Protein D (PD) - <6S and <6NS groups.

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination -<6S and <6NS Groups)

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination -<6S and <6NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination -<6S and <6NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination -<6S and <6NS Groups)

Secondary: Number of subjects with any unsolicited adverse events (AEs) (<6S, <6NS, 7-11S, 7-11NS Groups)

Secondary: Number of subjects with any unsolicited adverse events (AEs) (<6S, <6NS, 7-11S, 7-11NS Groups)

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

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

Secondary: Number of subjects with any unsolicited adverse events (AEs) (12-23S and 12-23NS Groups)

Secondary: Number of subjects with any unsolicited adverse events (AEs) (12-23S and 12-23NS Groups)

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Booster vaccination - <6S, <6NS, 7-11S, 7-11NS Groups).

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Booster vaccination - <6S, <6NS, 7-11S, 7-11NS Groups).

Secondary: Number of subjects with any and Grade 3 solicited local symptoms.(12-23S and 12-23NS Groups)

Secondary: Number of subjects with any and Grade 3 solicited local symptoms.(12-23S and 12-23NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination - 7-11S and 7-11NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (Primary vaccination - 7-11S and 7-11NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms. (Booster vaccination – <6S, <6NS, 7-11S, 7-11NS groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms. (Booster vaccination – <6S, <6NS, 7-11S, 7-11NS groups)

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination – 7-11S and 7-11NS Groups)

Secondary: Number of subjects with any and Grade 3 solicited local symptoms (Primary vaccination – 7-11S and 7-11NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (12-23S and 12-23NS Groups)

Secondary: Number of subjects with any, Grade 3 and related solicited general symptoms (12-23S and 12-23NS Groups)

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A - <6S and <6NS groups.

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A - <6S and <6NS groups.

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 7-11S and 7-11NS group.

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 7-11S and 7-11NS group.

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 7-11S and 7-11NS groups.

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 7-11S and 7-11NS groups.

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 12-23S and 12-23NS group.

Secondary: Concentrations of antibodies against Vaccine Pneumococcal Serotypes - 12-23S and 12-23NS group.

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 12-23S and 12-23NS groups.

Secondary: Concentrations of antibodies against Cross-reactive Pneumococcal Serotype 6A and 19A – 12-23S and 12-23NS groups.

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes - <6S and <6NS groups.

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes - <6S and <6NS groups.

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- <6S and <6NS groups

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- <6S and <6NS groups

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 7-11S and 7-11NS groups.

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 7-11S and 7-11NS groups.

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 7-11S and 7-11NS groups

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 7-11S and 7-11NS groups

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 12-23S and 12-23NS groups.

Secondary: Opsonophagocytic Titers Against Vaccine Pneumococcal Serotypes – 12-23S and 12-23NS groups.

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 12-23S and 12-23NS groups

Secondary: Opsonophagocytic Titers against Cross-reactive Pneumococcal Serotypes 6A and 19A.- 12-23S and 12-23NS groups

Secondary: Concentrations of Antibodies against Protein D (PD) – 7-11S and 7-11NS groups.

Secondary: Concentrations of Antibodies against Protein D (PD) – 7-11S and 7-11NS groups.

Secondary: Concentrations of Antibodies against Protein D (PD) – 12-23S and 12-23NS groups.

Secondary: Concentrations of Antibodies against Protein D (PD) – 12-23S and 12-23NS groups.

Secondary: Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT) - <6S and <6NS groups

Secondary: Concentrations of Antibodies Against Diphtheria Toxoid (DT) and Tetanus Toxoid (TT) - <6S and <6NS groups

Secondary: Concentrations of Antibodies against Bordetella Pertussis (BPT) - <6S and <6NS groups

Secondary: Concentrations of Antibodies against Bordetella Pertussis (BPT) - <6S and <6NS groups

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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