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Clinical Trial Results:
A phase 2b, randomized, controlled, observer-blind, multi-center study to evaluate safety and immunogenicity of different formulations of GSK Biologicals’ Meningococcal ACWY conjugate vaccine (GSK3536820A and Menveo) administered to healthy adolescents and young adults 10 to 40 years of age.

Summary
EudraCT number	2017-003456-23
Trial protocol	EE FI ES FR Outside EU/EEA
Global end of trial date	22 Oct 2020

Results information
Results version number	v1(current)
This version publication date	05 Mar 2021
First version publication date	05 Mar 2021
Other versions

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

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Trial information

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Sponsor protocol code

207467

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

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

Public contact

GSK Response Center, GlaxoSmithKline, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 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

10 Dec 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

26 Jul 2019

Global end of trial reached?

Yes

Global end of trial date

22 Oct 2020

Was the trial ended prematurely?

Main objective of the trial

• To demonstrate non-inferiority of the MenACWY liquid product aged for approximately 24 months to that of MenACWY vaccine, as measured by hSBA GMTs directed against N. meningitidis serogroup A at Day 29 after a single dose vaccination. Criterion: Non-inferiority will be concluded if lower limit of the 2-sided 95% CI for ratio of hSBA GMTs against serogroup A between the MenACWY liquid vaccine aged for approximately 24 months and MenACWY vaccine is greater than 0.5. • To demonstrate non-inferiority of the MenACWY liquid vaccine aged for approximately 30 months to that of MenACWY vaccine, as measured by hSBA GMTs directed against N. meningitidis serogroup A at Day 29 after a single dose vaccination. Criterion: Non-inferiority will be concluded if lower limit of the 2-sided 95% CI for ratio of hSBA GMTs against serogroup A between the MenACWY liquid vaccine aged for approximately 30 months and the MenACWY vaccine is greater than 0.5.

Protection of trial subjects

All subjects were observed closely for at least 30 minutes following the administration of the vaccine, with appropriate medical treatment readily available in case of anaphylaxis. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that have no contraindications to any components of the vaccine. Safety was monitored for 6 months after vaccination.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Aug 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 217

Country: Number of subjects enrolled

Estonia: 176

Country: Number of subjects enrolled

Finland: 202

Country: Number of subjects enrolled

France: 155

Country: Number of subjects enrolled

Mexico: 135

Country: Number of subjects enrolled

Russian Federation: 267

Country: Number of subjects enrolled

South Africa: 119

Country: Number of subjects enrolled

Spain: 306

Country: Number of subjects enrolled

Turkey: 130

Worldwide total number of subjects

1707

EEA total number of subjects

839

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

274

Adolescents (12-17 years)

417

Adults (18-64 years)

1016

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Enrollment was defined with 2 parallel groups per phase, in a 2-phase staggered design: both experimental groups subjects receiving respectively investigational vaccine aged for approximately 24 months in phase 1, and same vaccine aged for approximately 30 months in phase 2. Both comparator groups subjects receiving not aged licensed vaccine.

Screening details

Out of the 1707 subjects enrolled in the study (inclusive of phase 1 and 2), only 1690 were exposed to the vaccination. Out of the 17 subjects excluded from study, 11 were not randomized, 5 were not administered any study treatment, 1 did not sign the informed consent form.

Number of subjects started

1707

Number of subjects completed

1690

Reason: Number of subjects

Not randomized: 11

Reason: Number of subjects

Treatment not administered: 5

Reason: Number of subjects

Informed consent form not signed: 1

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

This was an observer blind study

Are arms mutually exclusive

Yes

GSK3536820A ACWY_Liq24 Group

Arm description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 24 months, at Day 1 in the Study Phase1

Arm type

Experimental

Investigational medicinal product name

MenACWY liquid

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose administered on day 1 to all subjects in the experimental group

ACWY_1 Group

Arm description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase1.

Arm type

Active comparator

Investigational medicinal product name

MenACWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose administered on day 1 to all subjects in the comparator group

GSK3536820A ACWY_Liq30 Group

Arm description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 30 months, at Day 1 in the Study Phase 2.

Arm type

Experimental

Investigational medicinal product name

MenACWY liquid

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose administered on day 1 to all subjects in the experimental group

ACWY_2 Group

Arm description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase 2.

Arm type

Active comparator

Investigational medicinal product name

MenACWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose administered on day 1 to all subjects in the comparator group

Number of subjects in period 1 ^[1]	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Started	420	424	427	419
Completed	419	424	423	418
Not completed	1	0	4	1
Consent withdrawn by subject	-	-	1	-
Unknown reason	-	-	2	-
Lost to follow-up	1	-	1	1

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Number of subjects reported in the baseline period are the actual number of subjects who were vaccinated, as compared to the number enrolled (started) in the study.

Baseline characteristics

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Reporting group title

GSK3536820A ACWY_Liq24 Group

Reporting group description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 24 months, at Day 1 in the Study Phase1

Reporting group title

ACWY_1 Group

Reporting group description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase1.

Reporting group title

GSK3536820A ACWY_Liq30 Group

Reporting group description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 30 months, at Day 1 in the Study Phase 2.

Reporting group title

ACWY_2 Group

Reporting group description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase 2.

Reporting group values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group	Total
Number of subjects	420	424	427	419	1690
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	22.5 ± 9.4	22.2 ± 9.6	22.3 ± 9.8	22.0 ± 9.3	-
Sex: Female, Male
Units: Participants
Female	232	242	259	228	961
Male	188	182	168	191	729
Race/Ethnicity, Customized
Units: Subjects
American Indian Or Alaska Native	0	1	1	2	4
Asian	4	4	2	3	13
Black Or African American	26	22	30	26	104
Other	58	54	83	84	279
White	332	343	311	304	1290

End points

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Reporting group title

GSK3536820A ACWY_Liq24 Group

Reporting group description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 24 months, at Day 1 in the Study Phase1

Reporting group title

ACWY_1 Group

Reporting group description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase1.

Reporting group title

GSK3536820A ACWY_Liq30 Group

Reporting group description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 30 months, at Day 1 in the Study Phase 2.

Reporting group title

ACWY_2 Group

Reporting group description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase 2.

Primary: Adjusted Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup A for each vaccine group and between-group ratios

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End point title

Adjusted Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup A for each vaccine group and between-group ratios

End point description

hSBA titers against N. meningitidis serogroup A are calculated in terms of GMTs adjusted for pre-vaccination titer. Analysis is performed on the per protocol set for immunogenicity that includes subjects who received the vaccine did not have any protocol deviation leading to exclusion , who were not excluded due to other reasons defined prior to unblinding or analysis and had available immuno data for any serogroup and time point considered.

End point type

Primary

End point timeframe

At Day 29

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	363	373	356	349
Units: Titers
geometric mean (confidence interval 95%)	386.66 (319.47 to 467.97)	318.34 (264.14 to 383.67)	387.06 (322.72 to 464.24)	348.89 (290.09 to 419.61)

Non-inferiority-MenACWYliq24 vs MenACWY

Statistical analysis description

To demonstrate non-inferiority of the MenACWY liquid vaccine aged for approximately 24 months to that of currently licensed MenACWY vaccine, as measured by the adjusted hSBA GMTs directed against N. meningitidis serogroup A at Day 29 after a single dose vaccination

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

736

Analysis specification

Pre-specified

Analysis type

^[1]

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

1.57

Notes
[1] - Non-inferiority is concluded if the lower limit of the two sided 95% confidence interval (CI) for the hSBA GMT ratio for serogroup A between the MenACWY liquid vaccine aged for approximately 24 months and the licensed MenACWY vaccine is > 0.5.

Non-inferiority-MenACWYliq30 vs MenACWY

Statistical analysis description

To demonstrate non-inferiority of the MenACWY liquid vaccine aged for approximately 30 months to that of currently licensed MenACWY vaccine, as measured by the adjusted hSBA GMTs directed against N. meningitidis serogroup A at Day 29 after a single dose vaccination.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

705

Analysis specification

Pre-specified

Analysis type

^[2]

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

1.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.42

Notes
[2] - Non-inferiority is concluded if the lower limit of the two sided 95% CI for the hSBA GMT ratios for serogroup A between the MenACWY liquid vaccine aged for approximately 30 months and the licensed MenACWY vaccine is > 0.5. Non-inferiority hypotheses testing will be conducted sequentially, starting from MenACWY liquid vaccine aged for approximately 24 months and subsequently with MenACWY liquid vaccine aged for approximately 30 months.

Secondary: hSBA GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group ratios

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End point title

hSBA GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group ratios

End point description

hSBA titers were calculated in terms of GMTs, at Day 1 and Day 29, against each of the N. meningitidis serogroup A, C, W and Y. Analysis is performed on the per protocol set for immunogenicity that includes subjects who received the vaccine did not have any protocol deviation leading to exclusion , who were not excluded due to other reasons defined prior to unblinding or analysis and had available immuno data for any serogroup and time point considered.

End point type

Secondary

End point timeframe

At Day 1 and Day 29

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	394	398	395	392
Units: Titers
geometric mean (confidence interval 95%)
Meningitis A,Day 1(N=381,389,377,374)	3.01 (2.69 to 3.36)	2.91 (2.60 to 3.24)	3.34 (2.94 to 3.79)	3.16 (2.78 to 3.59)
Meningitis A,Day 29(N=363,373,356,349)	388.53 (320.61 to 470.84)	319.06 (264.39 to 385.03)	394.16 (326.72 to 475.50)	349 (288.45 to 422.27)
Meningitis C,Day 1(N=394,395,395,392)	8.59 (7.40 to 9.98)	7.06 (6.09 to 8.20)	9.05 (7.77 to 10.53)	8.7 (7.46 to 10.14)
Meningitis C,Day 29(N=385,377,376,377)	143.69 (109.13 to 189.20)	157.74 (119.39 to 208.42)	244.44 (182.20 to 327.96)	208.34 (154.96 to 280.11)
Meningitis W,Day 1(N=379,396,382,376)	6.23 (5.17 to 7.50)	5.8 (4.83 to 6.95)	5.69 (4.75 to 6.82)	5.74 (4.78 to 6.90)
Meningitis W,Day 29(N=372,388,374,366)	62.73 (49.93 to 78.81)	63.92 (51.11 to 79.94)	80.51 (64.66 to 100.24)	73.08 (58.45 to 91.36)
Meningitis Y,Day 1(N=390,398,391,385)	4.39 (3.78 to 5.10)	4.21 (3.63 to 4.89)	4.14 (3.58 to 4.79)	4.19 (3.62 to 4.86)
Meningitis Y,Day 29(N=379,390,386,377)	116.42 (94.03 to 144.15)	105.11 (85.17 to 129.71)	112.95 (91.55 to 139.34)	118.04 (95.27 to 146.25)

Serogroup C-Day 29,ACWYliq24 versus ACWY

Statistical analysis description

Between-groups ratio of adjusted hSBA GMTs and its 95% CI, between vaccine groups GSK3536820A ACWY_Liq24 and ACWY_1, at Day 29 against serogroup C

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.19

Serogroup W-Day 29,ACWYliq24 versus ACWY

Statistical analysis description

Between-groups ratio of adjusted hSBA GMTs and its 95% CI, between vaccine groups GSK3536820A ACWY_Liq24 and ACWY_1, at Day 29 against serogroup W

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.24

Serogroup Y-Day 29,ACWYliq24 versus ACWY

Statistical analysis description

Between-groups ratio of adjusted hSBA GMTs and its 95% CI, between vaccine groups GSK3536820A ACWY_Liq24 and ACWY_1, at Day 29 against serogroup Y

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.44

Serogroup C-Day 29,ACWYLiq30 versus ACWY

Statistical analysis description

Between-groups ratio of adjusted hSBA GMTs and its 95% CI, between vaccine groups GSK3536820A ACWY_Liq30 and ACWY_2, at Day 29 against serogroup C

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

1.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.64

Serogroup W-Day 29,ACWYliq30 versus ACWY

Statistical analysis description

Between-groups ratio of adjusted hSBA GMTs and its 95% CI, between vaccine groups GSK3536820A ACWY_Liq30 and ACWY_2, at Day 29 against serogroup W

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.45

Serogroup Y-Day 29,ACWYliq30 versus ACWY

Statistical analysis description

Between-groups ratio of adjusted hSBA GMTs and its 95% CI, between vaccine groups GSK3536820A ACWY_Liq30 and ACWY_2, at Day 29 against serogroup Y

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

ANCOVA

Parameter type

GMT ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.26

Secondary: Within-group Geometric Mean Ratios (GMRs) of GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group

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End point title

Within-group Geometric Mean Ratios (GMRs) of GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group

End point description

Within-group ratios of hSBA GMTs against each of the N.meningitidis serogroups A, C, W and Y at Day 29 compared to Day 1. Analysis is performed on the per protocol set for immunogenicity that includes subjects who received the vaccine did not have any protocol deviation leading to exclusion , who were not excluded due to other reasons defined prior to unblinding or analysis and had available immuno data for any serogroup and time point considered.

End point type

Secondary

End point timeframe

At Day 29

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	385	390	386	377
Units: Ratio
geometric mean (confidence interval 95%)
Meningitis A(N=363,373,356,349)	130.33 (105.49 to 161.02)	108.39 (88.14 to 133.30)	114.66 (93.75 to 140.22)	106.79 (87.05 to 131.01)
Meningitis C(N=385,377,376,377)	17.01 (13.00 to 22.25)	21.68 (16.52 to 28.46)	26.69 (20.22 to 35.22)	23.85 (18.04 to 31.54)
Meningitis W(N=372,388,374,366)	9.81 (7.84 to 12.27)	10.77 (8.65 to 13.41)	13.8 (11.08 to 17.19)	12.48 (9.98 to 15.61)
Meningitis Y(N=379,390,386,377)	26.53 (21.14 to 33.28)	25.23 (20.18 to 31.54)	27.18 (21.66 to 34.10)	28.49 (22.60 to 35.92)

No statistical analyses for this end point

Secondary: Percentages of subjects with ≥4 fold rise in hSBA antibody titers for each of the N.meningitidis serogroups A, C,W and Y for each vaccine group and between-group differences

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End point title

Percentages of subjects with ≥4 fold rise in hSBA antibody titers for each of the N.meningitidis serogroups A, C,W and Y for each vaccine group and between-group differences

End point description

The percentages of subjects with a ≥ 4-fold rise in post-vaccination hSBA (at Day 29 compared to Day 1) and associated 2-sided 95% Clopper-Pearson CIs are computed by group and N. meningitidis serogroups A, C, W and Y. A 4-fold rise in the hSBA titers is defined as: - for individuals, whose pre-vaccination titers are < the LOD (limit of detection), the post-vaccination titers must be ≥ 4-fold the LOD or ≥ the LLOQ (lower limit of quantitation) whichever is greater; - for individuals whose pre-vaccination titers are ≥ the LOD and ≤ the LLOQ, the post-vaccination titers must be at least four times the LLOQ; - for individuals whose pre-vaccination titers are > the LLOQ, the post-vaccination titers must be at least four times the pre-vaccination titer. Analysis is performed on the per protocol set for immunogenicity.

End point type

Secondary

End point timeframe

At Day 29

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	385	390	386	377
Units: Percentage of subjects
number (confidence interval 95%)
Meningitis A(N=363,373,356,349)	92.29 (89.04 to 94.81)	90.08 (86.59 to 92.92)	91.57 (88.19 to 94.24)	91.69 (88.28 to 94.36)
Meningitis C(N=385,377,376,377)	62.34 (57.29 to 67.20)	64.46 (59.39 to 69.29)	72.61 (67.80 to 77.05)	69.76 (64.85 to 74.36)
Meningitis W(N=372,388,374,366)	59.41 (54.23 to 64.44)	60.57 (55.51 to 65.46)	66.58 (61.55 to 71.34)	62.57 (57.39 to 67.54)
Meningitis Y(N=379,390,386,377)	71.77 (66.95 to 76.25)	73.33 (68.65 to 77.66)	74.35 (69.69 to 78.64)	77.19 (72.62 to 81.33)

Serogroup A-ACWY Liq24 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup A at Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

775

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

2.21

Confidence interval

level

95%

sides

2-sided

lower limit

-1.94

upper limit

6.4

Serogroup C-ACWY Liq24 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup C at Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

775

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-2.12

Confidence interval

level

95%

sides

2-sided

lower limit

-8.94

upper limit

4.72

Serogroup W-ACWY Liq24 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup W at Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

775

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-1.16

Confidence interval

level

95%

sides

2-sided

lower limit

-8.11

upper limit

5.8

Serogroup Y-ACWY Liq24 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup Y at Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

775

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-1.57

Confidence interval

level

95%

sides

2-sided

lower limit

-7.88

upper limit

4.74

Serogroup A-ACWY Liq30 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup A at Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

763

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-4.29

upper limit

4.07

Serogroup C-ACWY Liq30 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup C at Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

763

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

2.85

Confidence interval

level

95%

sides

2-sided

lower limit

-3.63

upper limit

9.3

Serogroup W-ACWY Liq30 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup W at Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

763

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

4.01

Confidence interval

level

95%

sides

2-sided

lower limit

-2.89

upper limit

10.88

Serogroup Y-ACWY Liq30 versus ACWY

Statistical analysis description

Between-group difference in percentage of subjects with a ≥ 4-fold rise in post-vaccination hSBA for N. meningitidis serogroup Y at Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

763

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-2.84

Confidence interval

level

95%

sides

2-sided

lower limit

-8.91

upper limit

3.26

Secondary: Percentages of subjects with hSBA antibody titers ≥8 against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group differences

Top of page

End point title

Percentages of subjects with hSBA antibody titers ≥8 against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group differences

End point description

For each vaccine group the percentage of subjects with hSBA titer ≥8 , and its associated two-sided 95% Clopper-Pearson CIs are computed for each of the N. meningitidis serogroups A, C, W and Y. Analysis is performed on the per protocol set for immunogenicity that includes subjects who received the vaccine did not have any protocol deviation leading to exclusion , who were not excluded due to other reasons defined prior to unblinding or analysis and had available immuno data for any serogroup and time point considered.

End point type

Secondary

End point timeframe

At Day 1 and Day 29

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	394	398	395	392
Units: Percentage of subjects
number (confidence interval 95%)
Meningitis A,Day 1(N=381,389,377,374)	12.07 (8.98 to 15.77)	10.28 (7.45 to 13.74)	13.53 (10.24 to 17.40)	12.03 (8.91 to 15.77)
Meningitis A,Day 29(N=378,384,377,367)	93.65 (90.70 to 95.89)	92.19 (89.03 to 94.67)	93.37 (90.37 to 95.66)	94.01 (91.06 to 96.21)
Meningitis C,Day 1(N=394,395,395,392)	48.48 (43.44 to 53.53)	41.52 (36.61 to 46.55)	50.63 (45.59 to 55.67)	50.26 (45.19 to 55.31)
Meningitis C,Day 29(N=388,382,379,379)	77.58 (73.10 to 81.63)	78.01 (73.52 to 82.06)	84.17 (80.10 to 87.70)	82.85 (78.67 to 86.51)
Meningitis W,Day 1(N=379,396,382,376)	31.66 (27.01 to 36.61)	28.54 (24.14 to 33.26)	28.8 (24.30 to 33.62)	30.05 (25.46 to 34.96)
Meningitis W,Day 29(N=389,392,389,384)	79.43 (75.07 to 83.34)	80.87 (76.62 to 84.64)	85.86 (82.00 to 89.17)	81.77 (77.54 to 85.50)
Meningitis Y,Day 1(N=390,398,391,385)	22.82 (18.75 to 27.31)	21.86 (17.90 to 26.25)	21.48 (17.51 to 25.89)	22.34 (18.27 to 26.83)
Meningitis Y,Day 29(N=384,392,393,386)	87.5 (83.77 to 90.64)	85.46 (81.57 to 88.80)	88.04 (84.42 to 91.08)	87.56 (83.85 to 90.69)

Serogroup A-Day1,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup A on Day 1.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.79

Confidence interval

level

95%

sides

2-sided

lower limit

-2.69

upper limit

6.32

Serogroup C-Day1,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup C on Day 1.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

6.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

13.84

Serogroup W-Day1,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup W on Day 1.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

3.13

Confidence interval

level

95%

sides

2-sided

lower limit

-3.33

upper limit

9.58

Serogroup Y-Day1,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup Y on Day 1.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

-4.86

upper limit

6.8

Serogroup A-Day29,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup A on Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.46

Confidence interval

level

95%

sides

2-sided

lower limit

-2.24

upper limit

5.22

Serogroup C-Day29,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup C on Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.43

Confidence interval

level

95%

sides

2-sided

lower limit

-6.32

upper limit

5.46

Serogroup W-Day29,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup W on Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-1.43

Confidence interval

level

95%

sides

2-sided

lower limit

-7.05

upper limit

4.18

Serogroup Y-Day29,ACWYliq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup Y on Day 29.

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

2.04

Confidence interval

level

95%

sides

2-sided

lower limit

-2.81

upper limit

6.9

Serogroup A-Day1,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup A on Day 1.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.32

upper limit

6.33

Serogroup C-Day1,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup C on Day 1.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

-6.6

upper limit

7.35

Serogroup W-Day1,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup W on Day 1.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-1.26

Confidence interval

level

95%

sides

2-sided

lower limit

-7.75

upper limit

5.23

Serogroup Y-Day1,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup Y on Day 1.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.85

Confidence interval

level

95%

sides

2-sided

lower limit

-6.69

upper limit

4.98

Serogroup A-Day29,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup A on Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-4.24

upper limit

2.96

Serogroup C-Day29,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup C on Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.32

Confidence interval

level

95%

sides

2-sided

lower limit

-3.99

upper limit

6.64

Serogroup W-Day29,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 the N. meningitidis serogroup W on Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

4.09

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

9.33

Serogroup Y-Day29,ACWYliq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥8 for the N. meningitidis serogroup Y on Day 29.

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

-4.16

upper limit

5.13

Secondary: Percentages of subjects with hSBA titers ≥LLOQ against each of the N. meningitidis serogroups A, C, W and Y for each vaccine group, and between-group differences

Top of page

End point title

Percentages of subjects with hSBA titers ≥LLOQ against each of the N. meningitidis serogroups A, C, W and Y for each vaccine group, and between-group differences

End point description

For each vaccine group the percentages of subjects with hSBA titer ≥LLOQ, and its associated two-sided 95% Clopper-Pearson CIs are computed for each of the N. meningitidis serogroups A, C, W and Y. Analysis is performed on the per protocol set for immunogenicity that includes subjects who received the vaccine did not have any protocol deviation leading to exclusion , who were not excluded due to other reasons defined prior to unblinding or analysis and had available immuno data for any serogroup and time point considered.

End point type

Secondary

End point timeframe

At Day 1 and Day 29

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	394	398	395	392
Units: Percentage of subjects
number (confidence interval 95%)
Meningitis A,Day 1(N=381,389,377,374)	12.86 (9.67 to 16.64)	11.57 (8.56 to 15.17)	15.38 (11.89 to 19.43)	13.64 (10.32 to 17.54)
Meningitis A,Day 29(N=378,384,377,367)	93.92 (91.01 to 96.10)	92.19 (89.03 to 94.67)	93.37 (90.37 to 95.66)	94.01 (91.06 to 96.21)
Meningitis C,Day 1(N=394,395,395,392)	55.84 (50.78 to 60.81)	48.61 (43.58 to 53.66)	61.01 (56.01 to 65.85)	57.14 (52.08 to 62.10)
Meningitis C,Day 29(N=388,382,379,379)	79.38 (75.01 to 83.30)	80.37 (76.02 to 84.23)	84.7 (80.67 to 88.17)	84.7 (80.67 to 88.17)
Meningitis W,Day 1(N=379,396,382,376)	32.45 (27.76 to 37.42)	28.54 (24.14 to 33.26)	29.32 (24.80 to 34.16)	30.05 (25.46 to 34.96)
Meningitis W,Day 29(N=389,392,389,384)	79.43 (75.07 to 83.34)	80.87 (76.62 to 84.64)	85.86 (82.00 to 89.17)	81.77 (77.54 to 85.50)
Meningitis Y,Day 1(N=390,398,391,385)	24.36 (20.18 to 28.93)	22.86 (18.83 to 27.31)	21.74 (17.75 to 26.16)	22.86 (18.76 to 27.38)
Meningitis Y,Day 29(N=384,392,393,386)	88.28 (84.63 to 91.32)	86.22 (82.41 to 89.48)	88.3 (84.70 to 91.30)	87.56 (83.85 to 90.69)

Serogroup A-Day1,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup A at Day 1

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

-3.37

upper limit

5.99

Serogroup C-Day1,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup C at Day 1

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

7.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

14.13

Serogroup W-Day1,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup W at Day 1

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

3.92

Confidence interval

level

95%

sides

2-sided

lower limit

-2.57

upper limit

10.39

Serogroup Y-Day1,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup Y at Day 1

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.49

Confidence interval

level

95%

sides

2-sided

lower limit

-4.44

upper limit

7.44

Serogroup A-Day29,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup A at Day 29

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.73

Confidence interval

level

95%

sides

2-sided

lower limit

-1.94

upper limit

5.46

Serogroup C-Day29,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup C at Day 29

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.99

Confidence interval

level

95%

sides

2-sided

lower limit

-6.66

upper limit

4.7

Serogroup W-Day29,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup W at Day 29

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-1.43

Confidence interval

level

95%

sides

2-sided

lower limit

-7.05

upper limit

4.18

Serogroup Y-Day29,ACWY liq24 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup Y at Day 29

Comparison groups

GSK3536820A ACWY_Liq24 Group v ACWY_1 Group

Number of subjects included in analysis

792

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

2.06

Confidence interval

level

95%

sides

2-sided

lower limit

-2.67

upper limit

6.8

Serogroup A-Day1,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup A at Day 1

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

-3.32

upper limit

6.83

Serogroup C-Day1,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup C at Day 1

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

3.87

Confidence interval

level

95%

sides

2-sided

lower limit

-3

upper limit

10.71

Serogroup W-Day1,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup W at Day 1

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-7.24

upper limit

5.77

Serogroup Y-Day1,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup Y at Day 1

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-1.12

Confidence interval

level

95%

sides

2-sided

lower limit

-6.99

upper limit

4.75

Serogroup A-Day29,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup A at Day 29

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

-0.64

Confidence interval

level

95%

sides

2-sided

lower limit

-4.24

upper limit

2.96

Serogroup C-Day29,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup C at Day 29

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.16

upper limit

5.16

Serogroup W-Day29,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup W at Day 29

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

4.09

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

9.33

Serogroup Y-Day29,ACWY liq30 versus ACWY

Statistical analysis description

Between-group difference in percentages of subjects with hSBA titer ≥LLOQ for the N. meningitidis serogroup Y at Day 29

Comparison groups

GSK3536820A ACWY_Liq30 Group v ACWY_2 Group

Number of subjects included in analysis

787

Analysis specification

Pre-specified

Analysis type

Method

Miettinen and Nurminen score method

Parameter type

Difference in percentage of subjects

Point estimate

0.73

Confidence interval

level

95%

sides

2-sided

lower limit

-3.88

upper limit

5.37

Secondary: Number of subjects reported with any unsolicited adverse events (AEs) within 30 minutes after vaccination

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End point title

Number of subjects reported with any unsolicited adverse events (AEs) within 30 minutes after vaccination

End point description

An unsolicited adverse event (AE) is defined as any untoward medical occurrence in a subject or clinical investigation subject administered with a pharmaceutical product at any dose that does not necessarily have to have a causal relationship with this treatment. Analysis was performed on the unsolicited safety set that includes all enrolled subjects who received a study vaccination and reported unsolicited adverse events data for the defined period.

End point type

Secondary

End point timeframe

Within 30 minutes after vaccination at Day 1

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	420	424	427	419
Units: Participants	2	2	6	6

No statistical analyses for this end point

Secondary: Number of subjects reported with solicited local and systemic AEs

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End point title

Number of subjects reported with solicited local and systemic AEs

End point description

Assessed solicited local AEs were erythema, induration and pain at injection site. Assessed solicited systemic AEs were Arthralgia, chills, fatigue, fever (body temperature ≥38.0°C), headache, loss of appetite, myalgia and nausea. Analysis was performed on the solicited safety set that includes all enrolled subjects who received a study vaccination and reported solicited adverse events data for the defined period.

End point type

Secondary

End point timeframe

From Day 1 (6 hours) to Day 7 after vaccination

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	418	422	425	419
Units: Participants
Arthralgia	45	50	49	40
Chills	75	79	78	56
Erythema	48	51	58	40
Fatigue	174	175	149	147
Fever (Temperature >= 38 C)	15	18	15	12
Headache	164	151	169	157
Induration	50	51	54	39
Loss of Appetite	53	54	63	34
Myalgia	60	59	58	65
Nausea	54	48	42	46
Pain	189	181	202	192

No statistical analyses for this end point

Secondary: Number of subjects reported with other indicators of reactogenicity

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End point title

Number of subjects reported with other indicators of reactogenicity

End point description

Number of subjects reporting other indicators of reactogenicity such as use of analgesics/antipyretics within 7 days after any vaccination. Analysis was performed on the solicited safety set that includes all enrolled subjects who received a study vaccination and reported solicited adverse events data for the defined period.

End point type

Secondary

End point timeframe

From Day 1 to Day 7 after vaccination

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	418	422	425	419
Units: Participants
Analgesic/Antipyretic Prevention, No	357	374	366	369
Analgesic/Antipyretic Prevention, Yes	61	48	59	50
Analgesic/Antipyretic Treatment, No	328	340	349	350
Analgesic/Antipyretic Treatment, Yes	90	82	76	69

No statistical analyses for this end point

Secondary: Number of subjects reported with any unsolicited AEs within 29 days after vaccination

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End point title

Number of subjects reported with any unsolicited AEs within 29 days after vaccination

End point description

End point type

Secondary

End point timeframe

From Day 1 to Day 29 after vaccination

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	420	424	427	419
Units: Participants	77	91	101	97

No statistical analyses for this end point

Secondary: Number of subjects reported with serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs

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End point title

Number of subjects reported with serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs

End point description

Medically attended AEs are defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any medically attended AE(s) is occurrence of any medically attended AE(s) regardless of intensity grade or relation to vaccination. Serious adverse event is any congenital anomaly/birth defect in the offspring of a study subject or any untoward medical occurrence that results in death or life threatening or requires hospitalization or results in disability or incapacity. Analysis was performed on the unsolicited safety set that includes all enrolled subjects who received a study vaccination and reported unsolicited adverse events data for the defined period.

End point type

Secondary

End point timeframe

From Day 1 to Day 181 (during the entire study period)

End point values	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Number of subjects analysed	420	424	427	419
Units: Participants
Leading to withdrawal	0	0	0	0
SAEs	4	1	4	4
MAEs	88	69	81	77

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited AEs were collected from Day 1 to Day 7 after vaccination and Unsolicited AEs from Day 1 to Day 29 after vaccination. SAEs were collected from Day 1 to Day 181 (during the entire study period)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

GSK3536820A ACWY_Liq24 Group

Reporting group description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 24 months, at Day 1 in the Study Phase1

Reporting group title

ACWY_1 Group

Reporting group description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase1.

Reporting group title

GSK3536820A ACWY_Liq30 Group

Reporting group description

Healthy subjects receiving a single dose of the investigational MenACWY liquid vaccine formulation aged for approximately 30 months, at Day 1 in the Study Phase 2.

Reporting group title

ACWY_2 Group

Reporting group description

Healthy subjects receiving a single dose of the licensed GSK' MenACWY vaccine formulation (Menveo), not aged, at Day 1 in the Study Phase 2.

Serious adverse events	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 420 (0.95%)	1 / 424 (0.24%)	4 / 427 (0.94%)	4 / 419 (0.95%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Post procedural haemorrhage
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Soft tissue injury
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Phimosis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Tension headache
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Appendicitis noninfective
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Adnexa uteri pain
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst ruptured
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Otitis externa
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	GSK3536820A ACWY_Liq24 Group	ACWY_1 Group	GSK3536820A ACWY_Liq30 Group	ACWY_2 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	312 / 420 (74.29%)	314 / 424 (74.06%)	324 / 427 (75.88%)	317 / 419 (75.66%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
General disorders and administration site conditions
Administration site erythema
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Administration site induration
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Administration site pain
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Application site erythema
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Application site warmth
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Chills
subjects affected / exposed	77 / 420 (18.33%)	79 / 424 (18.63%)	78 / 427 (18.27%)	56 / 419 (13.37%)
occurrences all number	78	81	78	57
Discomfort
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Facial pain
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Fatigue
subjects affected / exposed	175 / 420 (41.67%)	175 / 424 (41.27%)	150 / 427 (35.13%)	147 / 419 (35.08%)
occurrences all number	175	179	157	150
Induration
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Injection site erythema
subjects affected / exposed	50 / 420 (11.90%)	51 / 424 (12.03%)	59 / 427 (13.82%)	42 / 419 (10.02%)
occurrences all number	51	52	68	47
Injection site haematoma
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	1	0	0	1
Injection site induration
subjects affected / exposed	52 / 420 (12.38%)	51 / 424 (12.03%)	54 / 427 (12.65%)	39 / 419 (9.31%)
occurrences all number	53	51	62	43
Injection site oedema
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	1	0	0
Injection site pain
subjects affected / exposed	190 / 420 (45.24%)	182 / 424 (42.92%)	205 / 427 (48.01%)	194 / 419 (46.30%)
occurrences all number	193	183	214	201
Injection site pruritus
subjects affected / exposed	2 / 420 (0.48%)	3 / 424 (0.71%)	2 / 427 (0.47%)	2 / 419 (0.48%)
occurrences all number	3	3	2	2
Injection site rash
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Injection site scab
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Malaise
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	1	0	1	0
Oedema
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Pain
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	2 / 427 (0.47%)	2 / 419 (0.48%)
occurrences all number	0	0	2	2
Pyrexia
subjects affected / exposed	20 / 420 (4.76%)	19 / 424 (4.48%)	19 / 427 (4.45%)	14 / 419 (3.34%)
occurrences all number	21	20	19	14
Vaccination site pain
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	1	1	0
Vessel puncture site induration
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Vessel puncture site pain
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Immune system disorders
Allergy to arthropod sting
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Drug hypersensitivity
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Reproductive system and breast disorders
Dysfunctional uterine bleeding
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Dysmenorrhoea
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	1 / 427 (0.23%)	4 / 419 (0.95%)
occurrences all number	1	0	1	4
Endometriosis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Polycystic ovaries
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Cough
subjects affected / exposed	2 / 420 (0.48%)	0 / 424 (0.00%)	2 / 427 (0.47%)	2 / 419 (0.48%)
occurrences all number	2	0	2	2
Dysphonia
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Epistaxis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Nasal congestion
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	1	0	1	2
Nasal obstruction
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	3 / 427 (0.70%)	1 / 419 (0.24%)
occurrences all number	0	1	3	1
Pharyngeal erythema
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Respiratory disorder
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Rhinitis allergic
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Rhinorrhoea
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	3 / 427 (0.70%)	0 / 419 (0.00%)
occurrences all number	1	0	3	0
Sneezing
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Psychiatric disorders
Bulimia nervosa
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Insomnia
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Irritability
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Contusion
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	0	0	1	1
Fall
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Hand fracture
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Joint dislocation
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Ligament sprain
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	1	1	0	1
Limb injury
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Nervous system disorders
Burning sensation
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Dizziness
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	1 / 427 (0.23%)	4 / 419 (0.95%)
occurrences all number	2	1	1	4
Epilepsy
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Headache
subjects affected / exposed	168 / 420 (40.00%)	155 / 424 (36.56%)	178 / 427 (41.69%)	162 / 419 (38.66%)
occurrences all number	177	164	200	188
Intercostal neuralgia
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Migraine
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	1	0	0	1
Paraesthesia
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	2 / 419 (0.48%)
occurrences all number	0	0	0	2
Presyncope
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	1	1	0
Sciatica
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Somnolence
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	1	0	1
Tremor
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	0	0	1	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Eye disorders
Eye paraesthesia
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Vision blurred
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	2	0	0	1
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Abdominal pain
subjects affected / exposed	4 / 420 (0.95%)	4 / 424 (0.94%)	4 / 427 (0.94%)	6 / 419 (1.43%)
occurrences all number	4	4	4	7
Abdominal pain lower
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Abdominal pain upper
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Dental caries
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Diarrhoea
subjects affected / exposed	3 / 420 (0.71%)	0 / 424 (0.00%)	6 / 427 (1.41%)	5 / 419 (1.19%)
occurrences all number	4	0	6	5
Enteritis
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	1	0	0
Gastritis
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	1	0	0
Nausea
subjects affected / exposed	54 / 420 (12.86%)	48 / 424 (11.32%)	43 / 427 (10.07%)	46 / 419 (10.98%)
occurrences all number	56	49	45	46
Odynophagia
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	2 / 427 (0.47%)	0 / 419 (0.00%)
occurrences all number	0	1	2	0
Oesophagitis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Toothache
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	1	0	0	1
Vomiting
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	1	0	1	1
Skin and subcutaneous tissue disorders
Dermal cyst
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Dermatitis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Dermatitis allergic
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Dermatitis atopic
subjects affected / exposed	2 / 420 (0.48%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	2	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Hand dermatitis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Ingrowing nail
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Pruritus
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Rash
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Renal and urinary disorders
Hypertonic bladder
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	50 / 420 (11.90%)	53 / 424 (12.50%)	49 / 427 (11.48%)	40 / 419 (9.55%)
occurrences all number	52	53	55	41
Back pain
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	5 / 427 (1.17%)	4 / 419 (0.95%)
occurrences all number	0	1	5	4
Muscle spasms
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	1	0	0
Myalgia
subjects affected / exposed	63 / 420 (15.00%)	62 / 424 (14.62%)	58 / 427 (13.58%)	65 / 419 (15.51%)
occurrences all number	63	62	63	68
Neck pain
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	0	0	1	1
Pain in extremity
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	0	0	1	1
Tendonitis
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Torticollis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Abscess oral
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Acute sinusitis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Balanitis candida
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Bronchitis
subjects affected / exposed	0 / 420 (0.00%)	3 / 424 (0.71%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	3	0	1
Conjunctivitis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Enterobiasis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Gastroenteritis
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	1 / 427 (0.23%)	1 / 419 (0.24%)
occurrences all number	1	1	1	1
Helicobacter infection
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Herpes simplex
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	1	0	1	0
Hordeolum
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Influenza
subjects affected / exposed	1 / 420 (0.24%)	2 / 424 (0.47%)	3 / 427 (0.70%)	3 / 419 (0.72%)
occurrences all number	1	2	3	3
Injection site cellulitis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Laryngitis
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Nasopharyngitis
subjects affected / exposed	7 / 420 (1.67%)	15 / 424 (3.54%)	6 / 427 (1.41%)	6 / 419 (1.43%)
occurrences all number	7	15	7	6
Oral candidiasis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Oral herpes
subjects affected / exposed	1 / 420 (0.24%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	1	0	0
Otitis media
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	1 / 427 (0.23%)	0 / 419 (0.00%)
occurrences all number	0	0	1	0
Paronychia
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Pharyngitis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	2 / 427 (0.47%)	1 / 419 (0.24%)
occurrences all number	1	0	3	1
Pharyngitis streptococcal
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Pharyngotonsillitis
subjects affected / exposed	2 / 420 (0.48%)	0 / 424 (0.00%)	1 / 427 (0.23%)	2 / 419 (0.48%)
occurrences all number	2	0	1	2
Pneumonia
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	1	0	0	1
Respiratory tract infection
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	2 / 419 (0.48%)
occurrences all number	0	1	0	2
Respiratory tract infection viral
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Rhinitis
subjects affected / exposed	3 / 420 (0.71%)	4 / 424 (0.94%)	5 / 427 (1.17%)	7 / 419 (1.67%)
occurrences all number	3	4	5	7
Sinusitis
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	2 / 419 (0.48%)
occurrences all number	0	1	0	2
Tonsillitis
subjects affected / exposed	2 / 420 (0.48%)	0 / 424 (0.00%)	0 / 427 (0.00%)	2 / 419 (0.48%)
occurrences all number	2	0	0	2
Tracheitis
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0
Tracheobronchitis
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Upper respiratory tract infection
subjects affected / exposed	8 / 420 (1.90%)	8 / 424 (1.89%)	7 / 427 (1.64%)	4 / 419 (0.95%)
occurrences all number	8	8	7	4
Upper respiratory tract infection bacterial
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Urethritis
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	0	1	0	0
Urinary tract infection
subjects affected / exposed	0 / 420 (0.00%)	2 / 424 (0.47%)	1 / 427 (0.23%)	2 / 419 (0.48%)
occurrences all number	0	2	1	2
Viral infection
subjects affected / exposed	0 / 420 (0.00%)	1 / 424 (0.24%)	3 / 427 (0.70%)	0 / 419 (0.00%)
occurrences all number	0	1	3	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 420 (0.00%)	0 / 424 (0.00%)	0 / 427 (0.00%)	1 / 419 (0.24%)
occurrences all number	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	54 / 420 (12.86%)	54 / 424 (12.74%)	63 / 427 (14.75%)	34 / 419 (8.11%)
occurrences all number	55	56	64	36
Iron deficiency
subjects affected / exposed	1 / 420 (0.24%)	0 / 424 (0.00%)	0 / 427 (0.00%)	0 / 419 (0.00%)
occurrences all number	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

17 Jan 2018

Two exclusion criteria were merged into one. Immunogenicity endpoints that were included in subgroup analysis were clarified.

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: Adjusted Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup A for each vaccine group and between-group ratios

Primary: Adjusted Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) against N. meningitidis serogroup A for each vaccine group and between-group ratios

Secondary: hSBA GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group ratios

Secondary: hSBA GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group ratios

Secondary: Within-group Geometric Mean Ratios (GMRs) of GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group

Secondary: Within-group Geometric Mean Ratios (GMRs) of GMTs against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group

Secondary: Percentages of subjects with ≥4 fold rise in hSBA antibody titers for each of the N.meningitidis serogroups A, C,W and Y for each vaccine group and between-group differences

Secondary: Percentages of subjects with ≥4 fold rise in hSBA antibody titers for each of the N.meningitidis serogroups A, C,W and Y for each vaccine group and between-group differences

Secondary: Percentages of subjects with hSBA antibody titers ≥8 against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group differences

Secondary: Percentages of subjects with hSBA antibody titers ≥8 against each of the N.meningitidis serogroups A,C,W and Y for each vaccine group and between-group differences

Secondary: Percentages of subjects with hSBA titers ≥LLOQ against each of the N. meningitidis serogroups A, C, W and Y for each vaccine group, and between-group differences

Secondary: Percentages of subjects with hSBA titers ≥LLOQ against each of the N. meningitidis serogroups A, C, W and Y for each vaccine group, and between-group differences

Secondary: Number of subjects reported with any unsolicited adverse events (AEs) within 30 minutes after vaccination

Secondary: Number of subjects reported with any unsolicited adverse events (AEs) within 30 minutes after vaccination

Secondary: Number of subjects reported with solicited local and systemic AEs

Secondary: Number of subjects reported with solicited local and systemic AEs

Secondary: Number of subjects reported with other indicators of reactogenicity

Secondary: Number of subjects reported with other indicators of reactogenicity

Secondary: Number of subjects reported with any unsolicited AEs within 29 days after vaccination

Secondary: Number of subjects reported with any unsolicited AEs within 29 days after vaccination

Secondary: Number of subjects reported with serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs

Secondary: Number of subjects reported with serious adverse events (SAEs), AEs leading to withdrawal and medically attended AEs

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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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