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Clinical Trial Results:
A phase III, randomized, controlled, observer-blind study to demonstrate effectiveness, immunogenicity and safety of GSK's meningococcal Group B and combined ABCWY vaccines when administered to healthy adolescents and young adults.

Summary
EudraCT number	2019-001666-15
Trial protocol	FI CZ EE Outside EU/EEA
Global end of trial date	13 Sep 2022

Results information
Results version number	v3(current)
This version publication date	06 Jan 2024
First version publication date	27 Mar 2023
Other versions	v1 , v2
Version creation reason

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

205416

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

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

Public contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

24 Oct 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Sep 2022

Global end of trial reached?

Yes

Global end of trial date

13 Sep 2022

Was the trial ended prematurely?

Main objective of the trial

•Effectiveness of rMenB+OMV NZ and MenABCWY vaccines -against a panel of N.meningitidis serogroup B strains at 1 month(M) after the 3 and 2-dose rMenB+OMV NZ series and last MenABCWY dose when compared to 1 M after MenACWY dose -As the percentages of subjects whose sera kill ≥70% of strains tested using enc-hSBA at 1 M after the 3 and 2-dose rMenB+OMV NZ series and 1 M after last MenABCWY dose •Lot-lot consistency of immune responses of 3 lots of MenACWY component of MenABCWY vaccine,as measured by hSBA GMTs at 1 M after last dose •Immunological non-inferiority: MenABCWY versus MenACWY as measured by percentages of subjects achieving a 4-fold rise in hSBA titers at 1 M after last MenABCWY dose and 1 M after MenACWY dose •Effectiveness non-inferiority: MenABCWY versus rMenB+OMV NZ in terms of percentage of samples with bactericidal serum activity at 1 M after last ABCWY dose and 1 M after 3 or 2 dose rMenB+OMV series •Safety and reactogenicity of MenB,MenABCWY and MenACWY vaccines

Protection of trial subjects

Vaccine administration is to be preceded by a review of the participants medical history (including previous vaccination and possible occurrence of undesirable events) and a general physical examination at the first visit and symptom-directed physical examination before subsequent vaccinations. Protocol procedures including blood sampling were to be done by a qualified healthcare professional. Vaccines/products will be administered only to eligible participants who had no contraindications to any components of the vaccines/products. Participants will be followed-up for 6 months after third vaccination/product administration. The participants will be observed closely for at least 30 minutes following the administration of the vaccine(s)/product(s), with appropriate medical treatment readily available in case of anaphylaxis and/or syncope.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Aug 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 295

Country: Number of subjects enrolled

Canada: 229

Country: Number of subjects enrolled

Czechia: 750

Country: Number of subjects enrolled

Estonia: 127

Country: Number of subjects enrolled

Finland: 819

Country: Number of subjects enrolled

Türkiye: 333

Country: Number of subjects enrolled

United States: 1085

Worldwide total number of subjects

3638

EEA total number of subjects

1696

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)

702

Adolescents (12-17 years)

1459

Adults (18-64 years)

1477

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

As pre-specified in protocol: -Participant flow, Baseline characteristics, AEs, Effectiveness, and immunogenicity data are presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group. - Lot-to-lot consistency analysis data are presented for individual ABCWY lot groups (ABCWY-1, ABCWY-2 and ABCWY-3).

Screening details

Out of 3657 participants enrolled,19 participants did not receive vaccination as they did not meet the eligibility criteria, therefore only 3638 participants were included in the Exposed Set and started the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind ^[1]

Roles blinded

Monitor, Data analyst

Blinding implementation details

Observer-blinded study. Recipients & study evaluators will be unaware of vaccine administered.

Are arms mutually exclusive

Yes

MenB_0_2_6 Group

Arm description

Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.

Arm type

Experimental

Investigational medicinal product name

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

Investigational medicinal product code

Other name

Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of MenACWY vaccine at Day 211

Investigational medicinal product name

Meningococcal Group B Vaccine (rMenB+OMV NZ)

Investigational medicinal product code

Other name

Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses of rMenB+OMV NZ vaccine at Day 1, Day 61 and Day 181

MenB_0_6 Group

Arm description

Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.

Arm type

Experimental

Investigational medicinal product name

Meningococcal Group B Vaccine (rMenB+OMV NZ)

Investigational medicinal product code

Other name

Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of rMenB+OMV NZ vaccine at Day 1 and Day 181

Investigational medicinal product name

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

Investigational medicinal product code

Other name

Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of MenACWY vaccine at Day 61

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of Placebo at Day 211

ABCWY_Pooled

Arm description

Participants received 2 doses of either MenABCWY Lot 1, Lot 2, or Lot 3 vaccine on Day 1 and Day 181 and 1 dose of placebo on Day 61. Participants received 1 dose of placebo on Day 211 to maintain blinding. To evaluate the effectiveness of 2 doses of the MenABCWY vaccines against rMenB+OMV and MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 dose of Placebo at Day 61 and Day 211

Investigational medicinal product name

Combined Meningococcal Groups A, B, C, W and Y vaccine (MenABCWY)

Investigational medicinal product code

MenABCWY

Other name

Pharmaceutical forms

Powder and suspension for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of MenABCWY vaccine at Day 1 and Day 181

ACWY Group

Arm description

Participants received 1 dose of MenACWY vaccine at Day 1,1 dose of placebo at Day 61 and 1 dose of rMenB+OMV NZ vaccine on Day 181. Participants received 1 dose of rMenB+OMV NZ vaccine on Day 211 as standard of care.

Arm type

Active comparator

Investigational medicinal product name

Meningococcal Groups A, C, W and Y Conjugate Vaccine (MenACWY)

Investigational medicinal product code

Other name

Menveo

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of MenACWY vaccine at Day 1

Investigational medicinal product name

Meningococcal Group B Vaccine (rMenB+OMV NZ)

Investigational medicinal product code

Other name

Bexsero

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of rMenB+OMV NZ vaccine at Day 181 and Day 211

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

1 dose of Placebo at Day 61

Notes
[1] - The roles blinded appear to be inconsistent with a double blind trial.
Justification: This is an Observer-blinded study. Recipients & study evaluators were unaware of the vaccine administered.

Number of subjects in period 1	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Started	897	906	1657	178
Completed	797	811	1497	163
Not completed	100	95	160	15
Consent withdrawn by subject	46	38	54	7
Adverse event, non-fatal	7	6	11	1
Not specified	1	-	1	1
MIGRATED / MOVED FROM THE STUDY AREA	6	7	9	1
Lost to follow-up	32	36	69	4
Protocol deviation	8	8	16	1

Baseline characteristics

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Reporting group title

MenB_0_2_6 Group

Reporting group description

Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.

Reporting group title

MenB_0_6 Group

Reporting group description

Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.

Reporting group title

ABCWY_Pooled

Reporting group description

Reporting group title

ACWY Group

Reporting group description

Reporting group values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group	Total
Number of subjects	897	906	1657	178	3638
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	183	172	320	27	702
Adolescents (12-17 years)	349	368	666	76	1459
Adults (18-64 years)	365	366	671	75	1477
From 65-84 years	0	0	0	0	0
85 years and over	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	16.5 ± 4.7	16.5 ± 4.7	16.5 ± 4.7	16.9 ± 4.6	-
Sex: Female, Male
Units: Participants
Female	464	446	933	100	1943
Male	433	460	724	78	1695
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	5	5	3	0	13
Asian	43	60	71	9	183
Black or African American	33	29	59	6	127
Native Hawaiian or Other Pacific Islander	3	1	3	0	7
Other, Unspecified	17	20	29	1	67
White	796	791	1492	162	3241

End points

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Reporting group title

MenB_0_2_6 Group

Reporting group description

Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.

Reporting group title

MenB_0_6 Group

Reporting group description

Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.

Reporting group title

ABCWY_Pooled

Reporting group description

Reporting group title

ACWY Group

Reporting group description

Subject analysis set title

ABCWY-1 Group

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 2 doses of MenABCWY lot 1 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.

Subject analysis set title

ABCWY-2 Group

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 2 doses of MenABCWY lot 2 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.

Subject analysis set title

ABCWY-3 Group

Subject analysis set type

Per protocol

Subject analysis set description

Participants received 2 doses of MenABCWY lot 3 vaccine at Day 1 and Day 181 and 2 doses of placebo at Day 61 and Day 211.

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 3-dose (0,2,6-M), 2-dose(0,6-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY

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End point title

Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 3-dose (0,2,6-M), 2-dose(0,6-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY ^[1]

End point description

The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 3 doses in MenB_0_2_6 group and 1 month after the 2 dose schedule in MenB_0_6 group when compared to one dose of MenACWY vaccination in ACWY group, against a panel of N. meningitidis serogroup B strains was measured in terms of percentage of samples without bactericidal activity using endogenous complement human Serum Bactericidal Assay (enc-hSBA), which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains. Number of Participants analyzed = Total number of participants included in PPS. Analysis was performed on blood samples collected from Per Protocol Set (PPS).

End point type

Primary

End point timeframe

At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group, and Day 31 for ACWY group)

Notes
[1] - 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: As specified in the Protocol, the analysis assesses the effectiveness of the MenABCWY vaccine compared to the rMenB+OMV vaccine in terms of the percentage of samples with bactericidal serum activity.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ACWY Group
Number of subjects analysed	740	751	147
Units: Percentage of blood samples
number (not applicable)
Number of Blood samples (N=25596,26142,4374)	13.3	14.4	79

Statistical analysis 2

Statistical analysis description

To demonstrate the effectiveness of the rMenB+OMV NZ vaccine against a randomly selected panel of endemic US N. meningitidis serogroup B invasive disease strains as measured by bactericidal activity using enc-hSBA at 1 month after the 2-dose (0,6-M) schedule in MenB_0_6 group when compared to 1 month after the MenACWY dose in the ACWY group.

Comparison groups

MenB_0_6 Group v ACWY Group

Number of subjects included in analysis

898

Analysis specification

Pre-specified

Analysis type

other ^[2]

Method

Parameter type

Point estimate

81.8

Confidence interval

level

97.5%

sides

2-sided

lower limit

80.4

upper limit

83.1

Notes
[2] - Effectiveness of rMenB+OMV NZ vaccine is demonstrated if the LL of the 2-sided 97.5% CI for VE against the selected strain panel between the MenB_0_ 6 and the ACWY groups is above 65%. VE is defined as 1- RR = (1- percentage of samples without bactericidal serum activity at 1:4 dilution in MenB group / percentage of samples without bactericidal serum activity at 1:4 dilution in the ACWY group) x100 percentage.

Statistical analysis 1

Statistical analysis description

To demonstrate the effectiveness of the rMenB+OMV NZ vaccine against a randomly selected panel of endemic US N. meningitidis serogroup B invasive disease strains as measured by bactericidal activity using enc-hSBA at 1 month after the 3-dose (0,2,6-months) schedule in MenB_0_2_6 group when compared to 1 month after the MenACWY dose in the ACWY group.

Comparison groups

MenB_0_2_6 Group v ACWY Group

Number of subjects included in analysis

887

Analysis specification

Pre-specified

Analysis type

other ^[3]

Method

Parameter type

VE (Vaccine Effectiveness)

Point estimate

83.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

81.9

upper limit

84.4

Notes
[3] - Effectiveness of rMenB+OMV NZ vaccine is demonstrated if the LL of the 2-sided 97.5% CI for Vaccine Effectiveness (VE) against the selected strain panel between the MenB_0_2_6 and the ACWY groups is above 65%. VE is defined as 1- Risk Ratio (RR) = (1- percentage of samples without bactericidal serum activity at 1:4 dilution in MenB group / percentage of samples without bactericidal serum activity at 1:4 dilution in the ACWY group) x100 percentage.

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 2-dose (0,2-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY

Top of page

End point title

Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 2-dose (0,2-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY ^[4]

End point description

The effectiveness (test-based) of rMenB+OMV vaccine at 1 month after the 2 doses in MenB_0_2_6 group when compared to one dose of MenACWY vaccination in ACWY group, against a panel of N. meningitidis serogroup B strains was measured in terms of percentage of samples without bactericidal activity using endogenous complement human Serum Bactericidal Assay (enc-hSBA), which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains. Number of Participants analyzed = Total number of participants included in PPS. Analysis was performed on blood samples collected from Per Protocol Set (PPS).

End point type

Primary

End point timeframe

At 1 month after vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2-dose schedule] and Day 31 for ACWY group)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As specified in the Protocol, the analysis assesses the effectiveness of the MenABCWY vaccine compared to the rMenB+OMV vaccine in terms of the percentage of samples with bactericidal serum activity.

End point values	MenB_0_2_6 Group	ACWY Group
Number of subjects analysed	740	147
Units: Percentage of blood samples
number (not applicable)
Number of Blood samples (N=27569,4374)	16.8	79

Statistical analysis 1

Statistical analysis description

To demonstrate the effectiveness of the rMenB+OMV NZ vaccine against a randomly selected panel of endemic US N. meningitidis serogroup B invasive disease strains as measured by bactericidal activity using enc-hSBA at 1 month after the 2-dose (0,2-M) schedule in MenB_0_2_6 group when compared to 1 month after the MenACWY dose in the ACWY group.

Comparison groups

MenB_0_2_6 Group v ACWY Group

Number of subjects included in analysis

887

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Parameter type

Point estimate

78.7

Confidence interval

level

97.5%

sides

2-sided

lower limit

77.2

upper limit

80.1

Notes
[5] - Effectiveness of rMenB+OMV NZ vaccine is demonstrated if the LL of the 2-sided 97.5% CI for VE against the selected strain panel between the MenB_0_2_6 and the ACWY groups is above 65%. VE is defined as 1- RR = (1- percentage of samples without bactericidal serum activity at 1:4 dilution in MenB group / percentage of samples without bactericidal serum activity at 1:4 dilution in the ACWY group) x100 percentage.

Primary: Geometric mean titers (GMTs) against serogroups A, C, W and Y for each lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 month after the last vaccination of MenABCWY

Top of page

End point title

Geometric mean titers (GMTs) against serogroups A, C, W and Y for each lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 month after the last vaccination of MenABCWY

End point description

Immune response was measured in terms of hSBA GMTs directed against serogroups A, C, W and Y. As pre- specified in the protocol, the data reported in this outcome measures data were presented for individual lots to demonstrate the consistency of the immune response of 3 lots (ABCWY- 1 Group, ABCWY-2 Group, and ABCWY-3 Group) of the ACWY component of the MenABCWY vaccine. Analysis was performed on PPS.

End point type

Primary

End point timeframe

At 1 month after the last vaccination of MenABCWY (Day 211)

End point values	ABCWY-1 Group	ABCWY-2 Group	ABCWY-3 Group
Number of subjects analysed	452	449	458
Units: Titers
geometric mean (confidence interval 95%)
Men A (N=448,443,454)	336.4 (299.3 to 378.0)	349.9 (311.5 to 393.0)	390.4 (347.4 to 438.8)
Men C (N= 448,449,456)	1036.7 (877.6 to 1224.5)	1130.2 (958.1 to 1333.4)	888.4 (752.1 to 1049.2)
Men W (N= 452,449,458)	564.5 (497.9 to 639.9)	635.5 (561.0 to 719.9)	640.1 (564.6 to 725.6)
Men Y (N=451,449,457)	536.7 (464.5 to 620.2)	623.9 (540.4 to 720.2)	644.3 (557.6 to 744.6)

Statistical analysis 1

Statistical analysis description

To demonstrate lot-to-lot consistency of the immune responses of ABCWY-1 and ABCWY-2 lots of the MenACWY component of the MenABCWY vaccine, as measured by hSBA GMTs directed against serogroup A at 1 month after last vaccination (Day 211).

Comparison groups

ABCWY-1 Group v ABCWY-2 Group

Number of subjects included in analysis

901

Analysis specification

Pre-specified

Analysis type

equivalence ^[6]

Method

Parameter type

GMT ratio

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.1

Notes
[6] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y are within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 2

Statistical analysis description

To demonstrate lot-to-lot consistency of the immune responses of ABCWY-1 and ABCWY-3 lots of the MenACWY component of the MenABCWY vaccine, as measured by hSBA GMTs directed against serogroup A at 1 month after last vaccination (Day 211).

Comparison groups

ABCWY-1 Group v ABCWY-3 Group

Number of subjects included in analysis

910

Analysis specification

Pre-specified

Analysis type

equivalence ^[7]

Method

Parameter type

GMT ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

0.98

Notes
[7] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 5

Statistical analysis description

Comparison groups

ABCWY-1 Group v ABCWY-3 Group

Number of subjects included in analysis

910

Analysis specification

Pre-specified

Analysis type

equivalence ^[8]

Method

Parameter type

GMT ratio

Point estimate

1.17

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.41

Notes
[8] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 12

Statistical analysis description

To demonstrate lot-to-lot consistency of the immune responses of ABCWY-2 and ABCWY-3 lots of the MenACWY component of the MenABCWY vaccine, as measured by hSBA GMTs directed against serogroup Y at 1 month after last vaccination (Day 211).

Comparison groups

ABCWY-2 Group v ABCWY-3 Group

Number of subjects included in analysis

907

Analysis specification

Pre-specified

Analysis type

equivalence ^[9]

Method

Parameter type

GMT ratio

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.14

Notes
[9] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 7

Statistical analysis description

Comparison groups

ABCWY-1 Group v ABCWY-2 Group

Number of subjects included in analysis

901

Analysis specification

Pre-specified

Analysis type

equivalence ^[10]

Method

Parameter type

GMT ratio

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.02

Notes
[10] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y are within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 8

Statistical analysis description

Comparison groups

ABCWY-1 Group v ABCWY-3 Group

Number of subjects included in analysis

910

Analysis specification

Pre-specified

Analysis type

^[11]

Method

Parameter type

GMT ratio

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.02

Notes
[11] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 9

Statistical analysis description

Comparison groups

ABCWY-2 Group v ABCWY-3 Group

Number of subjects included in analysis

907

Analysis specification

Pre-specified

Analysis type

equivalence ^[12]

Method

Parameter type

GMT ratio

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.86

upper limit

1.14

Notes
[12] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 10

Statistical analysis description

Comparison groups

ABCWY-1 Group v ABCWY-2 Group

Number of subjects included in analysis

901

Analysis specification

Pre-specified

Analysis type

equivalence ^[13]

Method

Parameter type

GMT ratio

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.01

Notes
[13] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y are within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 11

Statistical analysis description

Comparison groups

ABCWY-1 Group v ABCWY-3 Group

Number of subjects included in analysis

910

Analysis specification

Pre-specified

Analysis type

equivalence ^[14]

Method

Parameter type

GMT ratio

Point estimate

0.83

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

0.98

Notes
[14] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 4

Statistical analysis description

Comparison groups

ABCWY-1 Group v ABCWY-2 Group

Number of subjects included in analysis

901

Analysis specification

Pre-specified

Analysis type

equivalence ^[15]

Method

Parameter type

GMT ratio

Point estimate

0.92

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

1.11

Notes
[15] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y are within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 3

Statistical analysis description

Comparison groups

ABCWY-2 Group v ABCWY-3 Group

Number of subjects included in analysis

907

Analysis specification

Pre-specified

Analysis type

equivalence ^[16]

Method

Parameter type

GMT ratio

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.02

Notes
[16] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Statistical analysis 6

Statistical analysis description

Comparison groups

ABCWY-2 Group v ABCWY-3 Group

Number of subjects included in analysis

907

Analysis specification

Pre-specified

Analysis type

equivalence ^[17]

Method

Parameter type

GMT ratio

Point estimate

1.27

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

1.54

Notes
[17] - Lot-to-lot consistency is claimed if the 2-sided 95% CIs for the ratio of hSBA GMTs of antibodies against each of the serogroups A, C, W and Y is within the [0.5;2.0] equivalence interval for each pair of lots.

Primary: Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the 2-dose (0,2-M) schedule of rMenB+OMV

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End point title

Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the 2-dose (0,2-M) schedule of rMenB+OMV ^[18] ^[19]

End point description

The effectiveness (responder-based) of the rMenB+OMV NZ vaccine was measured in terms of percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA, calculated based on Clopper Pearson method. Effectiveness is demonstrated if Lower Limit (LL) of the two-sided 97.5% CI for the percentages of subjects whose sera kill ≥70% of strains is above 65%. Analysis was performed on the FAS.

End point type

Primary

End point timeframe

At 1 month after vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2-dose schedule])

Notes
[18] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[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: As specified in the Protocol, the analysis assesses the effectiveness of the rMenB+OMV vaccine by assessing the percentages of subjects whose sera kill ≥70% of strains tested.

End point values	MenB_0_2_6 Group
Number of subjects analysed	831
Units: Percentage of participants
number (confidence interval 97.5%)	84.8 (81.8 to 87.5)

No statistical analyses for this end point

Primary: Percentage of participants whose sera kill Greater Than or Equal to (>=) 70% of the strains tested using enc-hSBA at 1 month after the 3-dose (0,2,6-M) schedule of rMenB+OMV and 2-dose(0,6-M) schedule of rMenB+OMV

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End point title

Percentage of participants whose sera kill Greater Than or Equal to (>=) 70% of the strains tested using enc-hSBA at 1 month after the 3-dose (0,2,6-M) schedule of rMenB+OMV and 2-dose(0,6-M) schedule of rMenB+OMV ^[20] ^[21]

End point description

End point type

Primary

End point timeframe

At 1 month after vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3-dose schedule] and MenB_0_6 group)

Notes
[20] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[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: As specified in the Protocol, the analysis assesses the effectiveness of the rMenB+OMV vaccine by assessing the percentages of subjects whose sera kill ≥70% of strains tested.

End point values	MenB_0_2_6 Group	MenB_0_6 Group
Number of subjects analysed	790	813
Units: Percentage of participants
number (confidence interval 97.5%)	93.4 (91.2 to 95.2)	89.8 (87.2 to 92)

No statistical analyses for this end point

Primary: Percentage of participants with 4-fold rise in hSBA titers against N. meningitidis serogroups A, C, W and Y at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group), relative to baseline

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End point title

Percentage of participants with 4-fold rise in hSBA titers against N. meningitidis serogroups A, C, W and Y at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group), relative to baseline ^[22]

End point description

Four-fold rise is defined as: If the pre-vaccination hSBA titer is < 4, then post-vaccination hSBA titer should be >= 16 . If the pre-vaccination hSBA titer is >= limit of detection (LOD) but < LL of quantification (LLOQ), then post-vaccination hSBA titer should be >= 4 times the LLOQ. If the pre-vaccination hSBA titer is >= LLOQ, then post-vaccination hSBA titer should be >= 4 times the pre-vaccination hSBA titer. As pre-specified in the protocol, data reported in this outcome measure were presented for ACWY group, ABCWY pooled group to evaluate the immunological non-inferiority of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY- 3 groups were pooled into a single group. Analysis was performed on PPS.

End point type

Primary

End point timeframe

At 1 month after vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 31 for the ACWY Group) compared to Day 1 (baseline)

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: As specified in the Protocol, the analysis assesses the effectiveness of the rMenB+OMV vaccine compared to one dose of MenACWY vaccination in the ACWY group.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	1196	119
Units: Percentage of participants
number (confidence interval 95%)
Men A (N=1170,112)	97.0 (95.9 to 97.9)	85.7 (77.8 to 91.6)
Men C (N=1189,114)	97.2 (96.1 to 98.1)	50.0 (40.5 to 59.5)
Men W (N=1185,115)	97.0 (95.9 to 97.9)	61.7 (52.2 to 70.6)
Men Y (N=1196,119)	96.7 (95.6 to 97.7)	69.7 (60.7 to 77.8)

Statistical Analysis 1

Statistical analysis description

To demonstrate the immunological non- inferiority of the MenABCWY vaccine compared to the MenACWY vaccine in participants without a previous MenACWY vaccination (unprimed) as measured by the percentages of participants, achieving a 4- fold rise in hSBA titers against N. meningitidis serogroup A at 1 month after the last MenABCWY vaccination (Day 211) and 1 month after the MenACWY vaccination.

Comparison groups

ABCWY_Pooled v ACWY Group

Number of subjects included in analysis

1315

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

Method

Parameter type

Difference in percentage of participants

Point estimate

11.29

Confidence interval

level

95%

sides

2-sided

lower limit

5.88

upper limit

19.01

Notes
[23] - Non-inferiority of MenABCWY vaccine is demonstrated if the LL of the 2-sided 95% CI for the difference in percentage of participants with 4-fold rise between the 2 groups is above -10%.

Statistical Analysis 3

Statistical analysis description

To demonstrate the immunological non- inferiority of the MenABCWY vaccine compared to the MenACWY vaccine in participants without a previous MenACWY vaccination (unprimed) as measured by the percentages of participants, achieving a 4- fold rise in hSBA titers against N. meningitidis serogroup W at 1 month after the last MenABCWY vaccination (Day 211) and 1 month after the MenACWY vaccination.

Comparison groups

ABCWY_Pooled v ACWY Group

Number of subjects included in analysis

1315

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

Method

Parameter type

Difference in percentage of participants

Point estimate

35.31

Confidence interval

level

95%

sides

2-sided

lower limit

26.88

upper limit

44.49

Notes
[24] - Non-inferiority of MenABCWY vaccine is demonstrated if the LL of the 2-sided 95% CI for the difference in percentage of participants with 4-fold rise between the 2 groups is above -10%.

Statistical Analysis 4

Statistical analysis description

To demonstrate the immunological non- inferiority of the MenABCWY vaccine compared to the MenACWY vaccine in participants without a previous MenACWY vaccination (unprimed) as measured by the percentages of participants, achieving a 4- fold rise in hSBA titers against N. meningitidis serogroup Y at 1 month after the last MenABCWY vaccination (Day 211) and 1 month after the MenACWY vaccination.

Comparison groups

ABCWY_Pooled v ACWY Group

Number of subjects included in analysis

1315

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

Method

Parameter type

Difference in percentage of participants

Point estimate

26.99

Confidence interval

level

95%

sides

2-sided

lower limit

19.38

upper limit

35.81

Notes
[25] - Non-inferiority of MenABCWY vaccine is demonstrated if the LL of the 2-sided 95% CI for the difference in percentage of participants with 4-fold rise between the 2 groups is above -10%.

Statistical Analysis 2

Statistical analysis description

To demonstrate the immunological non- inferiority of the MenABCWY vaccine compared to the MenACWY vaccine in participants without a previous MenACWY vaccination (unprimed) as measured by the percentages of participants, achieving a 4- fold rise in hSBA titers against N. meningitidis serogroup C at 1 month after the last MenABCWY vaccination (Day 211) and 1 month after the MenACWY vaccination.

Comparison groups

ABCWY_Pooled v ACWY Group

Number of subjects included in analysis

1315

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

Method

Parameter type

Difference in percentage of participants

Point estimate

47.22

Confidence interval

level

95%

sides

2-sided

lower limit

38.14

upper limit

56.3

Notes
[26] - Non-inferiority of MenABCWY vaccine is demonstrated if the LL of the 2-sided 95% CI for the difference in percentage of participants with 4-fold rise between the 2 groups is above -10%.

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group)

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End point title

Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group) ^[27]

End point description

The effectiveness (test-based) of 2 doses of MenABCWY vaccine when compared to 1 dose of MenACWY vaccine, against a panel of N. meningitidis serogroup B strains was measured in terms of percentage of samples without bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. As pre-specified in the protocol, data reported in this outcome measure were presented for ACWY group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY- 3 groups were pooled into a single group. Analysis was performed on blood samples collected from PPS.

End point type

Primary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 31 for the ACWY group)

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: As specified in the Protocol, the analysis assesses the effectiveness of the rMenB+OMV vaccine compared to one dose of MenACWY vaccination in the ACWY group.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	1356	147
Units: Percentage of blood samples
number (not applicable)
Number of Blood samples analyzed (N=25715,4374)	17.4	79

Statistical analysis 1

Statistical analysis description

To demonstrate the effectiveness of the MenABCWY vaccine against a randomly selected panel of endemic US N. meningitidis serogroup B invasive disease strains as measured by enc-hSBA at 1 month after the last MenABCWY vaccination (Day 211) when compared to 1 month after the MenACWY vaccination.

Comparison groups

ABCWY_Pooled v ACWY Group

Number of subjects included in analysis

1503

Analysis specification

Pre-specified

Analysis type

other ^[28]

Method

Parameter type

Point estimate

77.9

Confidence interval

level

95%

sides

2-sided

lower limit

76.6

upper limit

79.2

Notes
[28] - Effectiveness of MenABCWY vaccine is demonstrated if the LL of the 2-sided 95% CI for VE against the selected strain panel between the ABCWY and the ACWY groups is above 65%. VE is defined as 1- RR = (1- percentage of samples without bactericidal serum activity at 1:4 dilution in ABCWY_Pooled group / percentage of samples without bactericidal serum activity at 1:4 dilution in the ACWY group) x100 percentage.

Primary: Percentage of blood samples with bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (pooled lots) and 2-dose(0,2-M) schedule of rMenB+OMV

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End point title

Percentage of blood samples with bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (pooled lots) and 2-dose(0,2-M) schedule of rMenB+OMV ^[29]

End point description

The effectiveness was measured in terms of percentage of samples with bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 Group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on blood samples collected from PPS, which included participants who received at least 1 dose of the study treatment to which they were randomized and have post-vaccination data for the specified analysis at specified timepoints and did not have any protocol deviations that lead to exclusion from the PPS.

End point type

Primary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 91 for the MenB_0_2_6 Group [2-dose schedule])

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: As specified in the Protocol, the analysis assesses the effectiveness of the MenABCWY vaccine compared to the rMenB+OMV vaccine in terms of the percentage of samples with bactericidal serum activity.

End point values	MenB_0_2_6 Group	ABCWY_Pooled
Number of subjects analysed	740	1356
Units: Percentage of blood samples
number (not applicable)
Number of Blood samples Analyzed (27569, 25715)	83.1	82.5

Statistical analysis 1

Statistical analysis description

To demonstrate the non-inferiority of the effectiveness of the MenABCWY vaccine (0,6-months schedule) compared to the rMenB+OMV NZ vaccine (0,2-months) in terms of percentage of samples with bactericidal serum activity using enc-hSBA against a randomly selected panel of endemic US N. meningitidis serogroup B invasive disease strains.

Comparison groups

MenB_0_2_6 Group v ABCWY_Pooled

Number of subjects included in analysis

2096

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

Method

Parameter type

Difference in percentage of participants

Point estimate

-0.61

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

0.03

Notes
[30] - Non-inferiority of MenABCWY to rMenB+OMV NZ is demonstrated if LL of the 2-sided 95% CI for the difference in percentages of samples with bactericidal serum activity at 1:4 dilution is above -5%.

Primary: Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the last vaccination in the ABCWY Group (pooled lots)

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End point title

Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the last vaccination in the ABCWY Group (pooled lots) ^[31] ^[32]

End point description

The effectiveness (responder-based) of the MenABCWY vaccine is measured in terms of percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA, being calculated based on Clopper Pearson method. Effectiveness is demonstrated Lower Limit (LL) of the two-sided 97.5% CI for the percentages of subjects whose sera kill ≥70% of strains tested for MenABCWY is above 65%. Analysis was performed on the FAS.

End point type

Primary

End point timeframe

At 1 month after the last vaccination of MenABCWY (Day 211)

Notes
[31] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
[32] - 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: As specified in the Protocol, the analysis assesses the effectiveness of the MenABCWY vaccine.

End point values	ABCWY_Pooled
Number of subjects analysed	817
Units: Percentage of participants
number (confidence interval 95%)	84.1 (81.4 to 86.5)

No statistical analyses for this end point

Primary: Number of participants with any solicited local adverse events (AEs) after the first study intervention administration

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End point title

Number of participants with any solicited local adverse events (AEs) after the first study intervention administration ^[33]

End point description

Assessed solicited local adverse events were injection or administration site pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group. Analysis was performed on the Solicited Safety Set (SSS).

End point type

Primary

End point timeframe

During 7 days after the first study intervention administration occurring at Day 1

Notes
[33] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	885	894	1638	178
Units: participants
Pain	807	819	1503	67
Erythema	90	86	216	11
Swelling	87	89	217	11
Induration	60	64	150	7

No statistical analyses for this end point

Primary: Number of participants with any solicited local adverse events (AEs) after the second study intervention administration

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End point title

Number of participants with any solicited local adverse events (AEs) after the second study intervention administration ^[34]

End point description

End point type

Primary

End point timeframe

During 7 days after the second study intervention administration occurring at Day 61

Notes
[34] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	823	813	1511	161
Units: participants
Pain	714	224	205	30
Erythema	89	26	5	1
Swelling	99	22	5	1
Induration	67	19	6	0

No statistical analyses for this end point

Primary: Number of participants with any solicited local adverse events (AEs) after the third study intervention administration

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End point title

Number of participants with any solicited local adverse events (AEs) after the third study intervention administration ^[35]

End point description

Assessed solicited local adverse events were injection site pain, erythema, swelling, induration. Any = occurrence of the adverse event regardless of intensity grade. Any erythema and swelling = adverse event reported with a surface diameter greater than 0 millimeters. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group. Analysis was performed on the Solicited Safety Set (SSS).

End point type

Primary

End point timeframe

During 7 days after the third study intervention administration occurring at Day 181

Notes
[35] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	765	759	1428	148
Units: participants
Pain	677	676	1258	126
Erythema	118	87	168	11
Swelling	107	85	176	13
Induration	52	57	114	12

No statistical analyses for this end point

Primary: Number of participants with any solicited systemic AEs after the first study intervention administration

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End point title

Number of participants with any solicited systemic AEs after the first study intervention administration ^[36]

End point description

Assessed solicited systemic AEs were fatigue, nausea, myalgia, arthralgia, headache and fever [temperature >= 38.0°C]. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination. No solicited AEs were collected after vaccination on Day 211 because these vaccines were administered as part of standard of care and to maintain blinding. As pre- specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group. Analysis was performed on the Solicited Safety Set (SSS).

End point type

Primary

End point timeframe

During 7 days after the first study intervention administration occurring at Day 1

Notes
[36] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	885	894	1638	178
Units: participants
Fatigue	423	414	828	78
Nausea	112	111	242	27
Myalgia	92	106	242	13
Arthralgia	56	70	133	17
Headache	358	330	681	69
Fever (C)	19	17	55	3

No statistical analyses for this end point

Primary: Number of participants with any solicited systemic AEs after the second study intervention administration

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End point title

Number of participants with any solicited systemic AEs after the second study intervention administration ^[37]

End point description

End point type

Primary

End point timeframe

During 7 days after the second study intervention administration occurring at Day 61

Notes
[37] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	823	813	1511	161
Units: participants
Fatigue	372	228	345	36
Nausea	104	56	85	18
Myalgia	110	46	55	3
Arthralgia	72	332	35	6
Headache	301	223	332	31
Fever (C)	22	12	18	1

No statistical analyses for this end point

Primary: Number of participants with any solicited systemic AEs after the third study intervention administration

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End point title

Number of participants with any solicited systemic AEs after the third study intervention administration ^[38]

End point description

End point type

Primary

End point timeframe

During 7 days after the third study intervention administration occurring at Day 181

Notes
[38] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	765	759	1428	148
Units: participants
Fatigue	374	341	602	56
Nausea	94	84	147	14
Myalgia	106	109	168	17
Arthralgia	71	53	104	7
Headache	302	284	509	39
Fever (C)	21	23	27	2

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs after the first study intervention administration

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End point title

Number of participants with any unsolicited AEs after the first study intervention administration ^[39]

End point description

Unsolicited AEs are defined as any AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms were reported as an unsolicited AE. Any Unsolicited AEs (including Serious adverse events (SAEs), AEs leading to withdrawal, Adverse event of special interest (AESIs) and medically attended AEs were collected during 30 days after vaccination 1-3. For vaccination on Day 211 (Vaccination 4), conducted as part of standard of care and to maintain blinding, no eDiary data or all unsolicited AEs were collected for the 30 days following vaccination. However, SAEs, AEs leading to withdrawal, AESIs and medically attended AEs were collected throughout study duration. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group. Analysis was performed on the Unsolicited Safety Set (USS).

End point type

Primary

End point timeframe

During the 30 days after the first study intervention administration occurring at Day 1

Notes
[39] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	893	900	1648	178
Units: participants	90	124	217	29

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs after the second study intervention administration

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End point title

Number of participants with any unsolicited AEs after the second study intervention administration ^[40]

End point description

End point type

Primary

End point timeframe

During the 30 days after the second study intervention administration occurring at Day 61

Notes
[40] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	851	855	1579	170
Units: participants	106	88	160	15

No statistical analyses for this end point

Primary: Number of participants with any unsolicited AEs after the third study intervention administration

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End point title

Number of participants with any unsolicited AEs after the third study intervention administration ^[41]

End point description

End point type

Primary

End point timeframe

During the 30 days after the third study intervention administration occurring at Day 181

Notes
[41] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	815	823	1521	166
Units: participants	96	94	183	19

No statistical analyses for this end point

Primary: Number of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs

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End point title

Number of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs ^[42]

End point description

A SAEs is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity and is a congenital anomaly/birth defect in the offspring of a study subject. AESIs are predefined (serious or non-serious) AEs of scientific and medical concern specific to the product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate, because such an event might warrant further investigation to characterize and understand it. Medically attended AEs are symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 group, MenB_0_6 group, ACWY group, ABCWY pooled group. Analysis was performed on the Unsolicited Safety Set (USS).

End point type

Primary

End point timeframe

Throughout the study period (Day 1 to Day 361)

Notes
[42] - 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 this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	893	900	1648	178
Units: participants
SAEs	20	22	25	5
AEs leading to withdrawal	6	4	4	1
AESIs	1	1	6	0
medically attended AEs	238	288	479	44

No statistical analyses for this end point

Secondary: Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose and 3-dose (0,2,6-M), 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

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End point title

Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose and 3-dose (0,2,6-M), 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

End point description

The effectiveness of the 3 dose (0,2,6-M) and 2 dose (0,6-M ) schedule of rMenB+OMV NZ vaccine and 2 doses of MenABCWY vaccine when compared to 1 month after the MenACWY vaccination (Day 31), against a panel of N. meningitidis serogroup B strains is measured in terms of percentage of samples without bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains. Number of Participants analyzed = Total number of participants included in FAS. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group,ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 211 for the MenB_0_2_6 group [3 dose schedule], MenB_0_6 group, ABCWY_Pooled group and Day 31 for the MenACWY group)

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled	ACWY Group
Number of subjects analysed	790	813	817	136
Units: Percentage of blood samples
number (not applicable)
Meningitis B M10713 Ab (N= 252,247,251,45)	0.4	0.4	1.2	15.6
Meningitis B M08641 Ab (N= 229,259,237,29)	6.6	6.2	8	96.6
Meningitis B M12898 Ab (N= 242,265,249,41)	8.4	11.4	12.1	68.1
Meningitis B M09150 Ab (N= 249,222,273,36)	5.2	8.5	12.6	73
Meningitis B M09401 Ab (N= 243,275,288,49)	50.2	46.5	57	98
Meningitis B M07463 Ab (N= 259,274,256,49)	1.5	1.8	3.5	49
Meningitis B M10496 Ab (N= 263,261,257,47)	54.4	47.9	68.9	100
Meningitis B M14530 Ab (N= 241,257,284,37)	2.1	1.6	3.2	100
Meningitis B M15668 Ab (N= 237,270,262,49)	0.8	2.2	0.8	87.8
Meningitis B M14028 Ab (N= 246,282,283,37)	2.8	5.7	4.9	100
Meningitis B M09909 Ab (N= 244,265,261,42)	79.1	83.4	86.2	100
Meningitis B M14385 Ab (N= 235,237,259,43)	0.9	0.8	0	16.3
Meningitis B M07992 Ab (N= 237,252,274,36)	0.4	0	0.4	0
Meningitis B M09155 Ab (N= 234,255,230,45)	1.7	2	1.3	97.8
Meningitis B M13085 Ab (N= 256,253,255,44)	13.5	27.5	26.6	69.3
Meningitis B M18303 Ab (N= 241,252,264,40)	2.9	4	9.5	100
Meningitis B M18711 Ab (N= 252,237,262,33)	5.2	4.2	9.5	75.8
Meningitis B M15009 Ab (N= 262,254,242,37)	11.8	20.5	31.8	86.5
Meningitis B M07773 Ab (N= 269,262,251,35)	0.7	0.4	0.4	74.3
Meningitis B M09662 Ab (N= 267,266,255,48)	61.4	50.8	66.3	95.8
Meningitis B M18483 Ab (N= 228,233,222,37)	3	5.1	3.7	72.2
Meningitis B M11906 Ab (N= 264,271,260,39)	23.7	30.3	39.9	84.7
Meningitis B M14987 Ab (N= 250,274,270,35)	1.2	8.8	12.7	68.6
Meningitis B M12014 Ab (N= 249,270,254,46)	0.4	0.7	1.2	67.4
Meningitis B M18200 Ab (N= 228,247,242,47)	6.3	14.8	14.9	33.7
Meningitis B M08912 Ab (N= 225,247,237,40)	0.4	0	0	0
Meningitis B M16748 Ab (N= 262,252,260,45)	0.8	0	0	0
Meningitis B M08152 Ab (N= 208,215,223,35)	22.4	25.3	32.8	66.8
Meningitis B M09973 Ab (N= 252,270,247,48)	0.8	1.1	3	83.3
Meningitis B M15352 Ab (N= 237,249,245,33)	8.9	8.4	17.8	97
Meningitis B M15165 Ab (N= 249,250,240,42)	0	1.2	2.1	92.9
Meningitis B M08127 Ab (N= 269,250,287,51)	0.7	0.4	0.7	84.3
Meningitis B M18347 Ab (N= 234,262,239,44)	45.4	50.9	51.8	82.1
Meningitis B M12500 Ab (N= 223,253,241,43)	0.9	2.4	2.5	95.3
Meningitis B M07499 Ab (N= 242,251,256,51)	70.7	75.7	80.1	100
Meningitis B M09960 Ab (N= 243,247,251,33)	1.2	0	0	3
Meningitis B M18045 Ab (N= 236,251,272,41)	0	0.4	0	92.7
Meningitis B M10548 Ab (N= 234,243,261,58)	8.1	11.9	12.5	74.1
Meningitis B M09354 Ab (N= 246,240,241,40)	1.2	1.3	0	80
Meningitis B M11051 Ab (N= 246,282,247,46)	61	64.2	66.7	97.8
Meningitis B M10104 Ab (N= 247,241,239,41)	58.7	52.3	63.5	97.6
Meningitis B M13361 Ab (N= 258,268,250,34)	0.8	0.4	0.4	85.3
Meningitis B M11042 Ab (N= 217,249,254,43)	19.8	25.5	33.5	85.7
Meningitis B M18467 Ab (N= 255,223,250,47)	1.2	0.4	0.8	78.7
Meningitis B M11113 Ab (N= 255,253,269,51)	30.1	39.5	49.5	75.2
Meningitis B M07253 Ab (N= 260,245,255,40)	34.7	33.8	50.2	86.4
Meningitis B M07356 Ab (N= 235,235,266,29)	0.4	0	1.1	41.4
Meningitis B M10710 Ab (N= 254,253,270,40)	1.6	2	1.4	92.5
Meningitis B M17147 Ab (N= 261,279,214,41)	2.3	5.4	2.3	100
Meningitis B M14401 Ab (N= 241,266,253,43)	1.7	0.4	1.2	83.7
Meningitis B M14293 Ab (N= 251,247,224,47)	45.8	25.1	45.2	95.7
Meningitis B M08540 Ab (N= 258,261,222,34)	1.6	0.8	0	38.2
Meningitis B M07960 Ab (N= 277,241,241,39)	3.6	4.1	1.8	94.9
Meningitis B M16135 Ab (N= 254,230,257,41)	0	1.7	0.8	95.1
Meningitis B M14548 Ab (N= 267,266,274,38)	2.6	3.4	3.2	94.7
Meningitis B M09181 Ab (N= 228,276,240,43)	0	0.4	0.4	72.1
Meningitis B M14224 Ab (N= 248,279,277,40)	0.4	0.4	0	82.5
Meningitis B M07452 Ab (N= 260,260,245,47)	2.7	8.1	17.1	85.1
Meningitis B M13520 Ab (N= 217,222,242,30)	3.2	0.9	0	66.7
Meningitis B M09385 Ab (N= 228,252,265,32)	0.4	1.6	0	46.9
Meningitis B M14881 Ab (N= 240,278,277,40)	4.2	5.8	10	95
Meningitis B M13252 Ab (N= 279,241,262,50)	0.7	1.2	0.4	98
Meningitis B M07818 Ab (N= 232,244,228,43)	0.4	0.8	1.3	90.7
Meningitis B M09914 Ab (N= 281,257,258,49)	85.4	86.8	88.3	98
Meningitis B M15083 Ab (N= 231,262,241,40)	51.4	56.7	61	84.5
Meningitis B M11290 Ab (N= 264,266,221,34)	61.4	61.7	67.4	100
Meningitis B M14988 Ab (N= 241,269,246,40)	0.4	0	1.2	60
Meningitis B M10536 Ab (N= 228,223,260,36)	19.7	14.3	14.3	91.7
Meningitis B M08959 Ab (N= 252,241,258,47)	0.8	0.4	1.9	85.1
Meningitis B M08785 Ab (N= 251,249,260,39)	0.8	0.4	0.4	53.8
Meningitis B M07245 Ab (N= 238,248,230,43)	0	0	0.9	23.3
Meningitis B M19315 Ab (N= 262,254,255,34)	3.8	3.1	9.5	79.4
Meningitis B M14376 Ab (N= 234,220,222,41)	0	1.4	0	92.7
Meningitis B M08994 Ab (N= 226,253,233,31)	2.5	7.6	6.9	62.7
Meningitis B M11646 Ab (N= 241,224,250,36)	0	1.3	2	83.3
Meningitis B M13362 Ab (N= 259,228,231,49)	0	0.4	0.4	81.6
Meningitis B M08080 Ab (N= 236,247,242,45)	27.4	41	51.6	85.7
Meningitis B M08370 Ab (N= 265,262,251,43)	2.3	1.5	3.7	97.7
Meningitis B M08129 Ab (N= 245,254,257,28)	4.1	4.7	7	71.4
Meningitis B M07111 Ab (N= 231,254,270,33)	0.4	1.2	0.7	90.9
Meningitis B M07537 Ab (N= 241,242,263,47)	95.9	95.9	97.7	100
Meningitis B M13438 Ab (N= 255,262,282,50)	1.2	0.8	0	16
Meningitis B M10661 Ab (N= 246,275,273,33)	2	2.9	2.9	97
Meningitis B M10920 Ab (N= 247,252,275,34)	29.1	27.8	37.8	91.2
Meningitis B M15564 Ab (N= 240,273,263,40)	0.4	0.7	0.8	77.5
Meningitis B M10934 Ab (N= 273,241,256,36)	0.4	0.8	0.8	100
Meningitis B M09400 Ab (N= 254,281,279,39)	0.8	1.8	0.4	97.4
Meningitis B M08781 Ab (N= 221,258,229,28)	71.9	74.4	78.2	100
Meningitis B M09173 Ab (N= 238,249,247,42)	0.4	0.4	0.8	95.2
Meningitis B M14113 Ab (N= 228,255,264,42)	15.4	21.2	22	100
Meningitis B M08389 Ab (N= 254,259,250,45)	10.7	7	11.7	87.2
Meningitis B M16822 Ab (N= 239,233,264,34)	67.8	76.4	82.2	100
Meningitis B M10995 Ab (N= 268,258,239,47)	5.2	17.8	30.6	85.1
Meningitis B M08780 Ab (N= 236,259,260,40)	1.3	0.8	1.5	92.5
Meningitis B M09910 Ab (N= 247,246,257,43)	1.6	1.2	1.2	93
Meningitis B M08320 Ab (N= 262,238,253,45)	33.6	39.7	43.3	87
Meningitis B M14879 Ab (N= 239,242,247,47)	2.1	2.1	6.1	21.3
Meningitis B M09345 Ab (N= 251,257,282,48)	19.3	20.1	33.4	81.2
Meningitis B M14594 Ab (N= 245,241,238,44)	20.8	27.4	41.2	97.7
Meningitis B M07621 Ab (N= 251,260,263,40)	1.2	1.2	1.1	77.5
Meningitis B M13568 Ab (N= 261,264,253,40)	5.4	3.8	3.9	95
Meningitis B M18017 Ab (N= 246,247,258,31)	0.4	0	1.6	96.8
Meningitis B M08420 Ab (N= 243,255,256,40)	0.8	0.4	1.6	95
Meningitis B M07959 Ab (N= 236,237,254,35)	1.7	2.5	1.7	97.1
Meningitis B M06970 Ab (N= 236,261,253,32)	19.6	17.6	30.2	85.7
Meningitis B M10491 Ab (N= 239,262,227,39)	5.4	8.4	17	82.1
Meningitis B M13569 Ab (N= 221,243,247,31)	0.9	2.9	1.2	96.8
Meningitis B M10182 Ab (N= 229,234,256,44)	0.4	0	0	0
Meningitis B M13547 Ab (N= 251,258,238,44)	2.4	7	4.7	47.7
Meningitis B M15276 Ab (N= 231,231,259,41)	0.4	0	1.5	87.8

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold rise in hSBA titers against N.meningitidis group B strains at 1 month after last MenABCWY dose (ABCWY group-pooled lots) and 1 month afte 2-dose(0,2-M) schedule of rMenB+OMV NZ relative to baseline

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End point title

Percentage of participants with 4-fold rise in hSBA titers against N.meningitidis group B strains at 1 month after last MenABCWY dose (ABCWY group-pooled lots) and 1 month afte 2-dose(0,2-M) schedule of rMenB+OMV NZ relative to baseline ^[43]

End point description

The immunogenicity is measured as percentage of participants achieving a 4-fold rise in hSBA titers against N. meningitidis serogroup B indicator strains (M14459, 96217, M13520 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively). 4-fold rise per each indicator strain was defined as a post-vaccination hSBA titre ≥16 for participants with a pre-vaccination hSBA titre <4; a post-vaccination hSBA titre ≥4 times the LLOQ for participants with a pre-vaccination hSBA titre ≥LOD and <LLOQ; a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for participants with a pre-vaccination hSBA titre ≥ LLOQ. As pre-specified in the protocol, data reported in this outcome measure were presented for MenB_0_2_6 Group and ABCWY pooled group to evaluate the effectiveness of 2 doses of the MenABCWY vaccines against MenACWY vaccines, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. The analysis was performed on the PPS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 211 for the ABCWY_Pooled group and Day 91 for the MenB_0_2_6 Group [2-dose schedule]) compared to Day 1 (Baseline)

Notes
[43] - 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: As specified in the Protocol, the analysis assesses the immunological noninferiority of the MenABCWY vaccine compared to the rMenB+OMV vaccine.

End point values	MenB_0_2_6 Group	ABCWY_Pooled
Number of subjects analysed	719	678
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459) Ab (N=719,675)	74.7 (71.3 to 77.8)	79.7 (76.5 to 82.7)
NadA (96217) Ab (N=717,671)	96.4 (94.7 to 97.6)	92.7 (90.5 to 94.5)
NHBA (M13520) Ab (N=718,678)	58.6 (54.9 to 62.3)	61.9 (58.2 to 65.6)
PorA (NZ98/254) Ab (N=704,642)	53.3 (49.5 to 57.0)	42.2 (38.4 to 46.1)

No statistical analyses for this end point

Secondary: Percentage of blood samples without bactericidal serum activity using enc-hSBA against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

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End point title

Percentage of blood samples without bactericidal serum activity using enc-hSBA against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY ^[44]

End point description

The effectiveness of the 2 dose (0,2-M) schedule of rMenB+OMV NZ vaccine when compared to 1 month after the MenACWY vaccination (Day 31), against a panel of N. meningitidis serogroup B strains is measured in terms of percentage of samples without bactericidal activity using enc-hSBA, which provides a qualitative assessment (yes/no) of the presence of sufficient bactericidal antibodies in human sera to kill a meningococcal strain at a specific dilution of 1:4. Participants were randomly selected for testing against each strain therefore only a subset of participants were tested for each of the strains. Number of Participants analyzed = Total number of participants included in FAS. Analysis was performed on blood samples collected from FAS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 91 for the MenB_0_2_6 group [2 dose schedule] and Day 31 for the MenACWY group)

Notes
[44] - 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: As specified in the Protocol, the analysis assesses the effectiveness of the rMenB+OMV vaccine compared to one dose of MenACWY vaccination in the ACWY group.

End point values	MenB_0_2_6 Group	ACWY Group
Number of subjects analysed	893	173
Units: Percentage of blood samples
number (not applicable)
Meningitis B M10713 Ab (N=266,45)	1.9	15.6
Meningitis B M08641 Ab (N=250,29)	11.2	96.6
Meningitis B M12898 Ab (N=260,41)	12.4	69
Meningitis B M09150 Ab (N=250,36)	9.3	68.6
Meningitis B M09401 Ab (N=253,49)	47	98
Meningitis B M07463 Ab (N=265,49)	2.6	49
Meningitis B M10496 Ab (N=277,47)	50.5	100
Meningitis B M14530 Ab (N=254,37)	3.9	100
Meningitis B M15668 Ab (N=252,49)	0.4	87.8
Meningitis B M14028 Ab (N=257,37)	5.4	100
Meningitis B M09909 Ab (N=266,42)	82	100
Meningitis B M14385 Ab (N=227,43)	0	16.3
Meningitis B M07992 Ab (N=249,36)	0	0
Meningitis B M09155 Ab (N=243,45)	2.5	97.8
Meningitis B M13085 Ab (N=271,44)	21	66.4
Meningitis B M18303 Ab (N=252,40)	9.1	100
Meningitis B M18711 Ab (N=261,33)	7.7	75.8
Meningitis B M15009 Ab (N=243,37)	22.2	86.5
Meningitis B M07773 Ab (N=281,35)	1.1	74.3
Meningitis B M09662 Ab (N=284,48)	58.1	95.8
Meningitis B M18483 Ab (N=234,37)	4.3	77.3
Meningitis B M11906 Ab (N=277,39)	38.8	85.3
Meningitis B M14987 Ab (N=264,35)	10.7	62.3
Meningitis B M12014 Ab (N=267,46)	0.7	63.2
Meningitis B M18200 Ab (N=241,47)	12.1	34.4
Meningitis B M08912 Ab (N=246,40)	0	0
Meningitis B M16748 Ab (N=281,45)	0	0
Meningitis B M08152 Ab (N=224,35)	35.6	67.2
Meningitis B M09973 Ab (N=271,48)	1.5	83.3
Meningitis B M15352 Ab (N=219,33)	11.9	97
Meningitis B M15165 Ab (N=265,42)	0.8	92.9
Meningitis B M08127 Ab (N=285,51)	0.4	84.3
Meningitis B M18347 Ab (N=249,44)	60.5	80.4
Meningitis B M12500 Ab (N=236,43)	3.4	95.3
Meningitis B M07499 Ab (N=259,51)	81.1	100
Meningitis B M09960 Ab (N=251,33)	4.4	3
Meningitis B M18045 Ab (N=247,41)	0	92.7
Meningitis B M10548 Ab (N=244,58)	11.9	74.1
Meningitis B M09354 Ab (N=258,40)	0.4	80
Meningitis B M11051 Ab (N=270,46)	68.9	97.8
Meningitis B M10104 Ab (N=249,41)	61.8	97.6
Meningitis B M13361 Ab (N=269,34)	0.4	85.3
Meningitis B M11042 Ab (N=210,43)	30.1	84.2
Meningitis B M18467 Ab (N=272,47)	0.4	78.7
Meningitis B M11113 Ab (N=273,51)	43.1	75.6
Meningitis B M07253 Ab (N=274,40)	43.3	85.3
Meningitis B M07356 Ab (N=247,29)	0	41.4
Meningitis B M10710 Ab (N=269,40)	2.2	92.5
Meningitis B M17147 Ab (N=274,41)	5.1	100
Meningitis B M14401 Ab (N=251,43)	0.8	83.7
Meningitis B M14293 Ab (N=264,47)	36.4	95.7
Meningitis B M08540 Ab (N=271,34)	0.4	38.2
Meningitis B M07960 Ab (N=292,39)	4.1	94.9
Meningitis B M16135 Ab (N=263,41)	0.8	95.1
Meningitis B M14548 Ab (N=286,38)	2.8	94.7
Meningitis B M09181 Ab (N=252,43)	0	72.1
Meningitis B M14224 Ab (N=268,40)	0.7	82.5
Meningitis B M07452 Ab (N=267,47)	13.5	85.1
Meningitis B M13520 Ab (N=234,30)	0.9	66.7
Meningitis B M09385 Ab (N=230,32)	2.2	46.9
Meningitis B M14881 Ab (N=258,40)	14.7	95
Meningitis B M13252 Ab (N=286,50)	3.1	98
Meningitis B M07818 Ab (N=249,43)	0.4	90.7
Meningitis B M09914 Ab (N=293,49)	87.7	98
Meningitis B M15083 Ab (N=260,40)	63.7	78
Meningitis B M11290 Ab (N=278,34)	70.5	100
Meningitis B M14988 Ab (N=251,40)	0.4	60
Meningitis B M10536 Ab (N=241,36)	23.2	91.7
Meningitis B M08959 Ab (N=267,47)	0.4	85.1
Meningitis B M08785 Ab (N=262,39)	0.4	53.8
Meningitis B M07245 Ab (N=254,43)	0	23.3
Meningitis B M19315 Ab (N=270,34)	6.3	79.4
Meningitis B M14376 Ab (N=269,41)	0	92.7
Meningitis B M08994 Ab (N=233,31)	8.9	55.7
Meningitis B M11646 Ab (N=252,36)	1.6	83.3
Meningitis B M13362 Ab (N=272,49)	1.5	81.6
Meningitis B M08080 Ab (N=244,45)	46.8	87.1
Meningitis B M08370 Ab (N=280,43)	3.9	97.7
Meningitis B M08129 Ab (N=242,28)	7.4	71.4
Meningitis B M07111 Ab (N=244,33)	0.4	90.9
Meningitis B M07537 Ab (N=253,47)	96.4	100
Meningitis B M13438 Ab (N=263,50)	0.4	16
Meningitis B M10661 Ab (N=259,33)	2.7	97
Meningitis B M10920 Ab (N=259,34)	50.2	91.2
Meningitis B M15564 Ab (N=258,40)	0.8	77.5
Meningitis B M10934 Ab (N=286,36)	0	100
Meningitis B M09400 Ab (N=261,39)	1.1	97.4
Meningitis B M08781 Ab (N=223,28)	75.8	100
Meningitis B M09173 Ab (N=244,42)	0	95.2
Meningitis B M14113 Ab (N=244,42)	28.3	100
Meningitis B M08389 Ab (N=258,45)	1.9	86.7
Meningitis B M16822 Ab (N=240,34)	85	100
Meningitis B M10995 Ab (N=282,47)	16.3	85.1
Meningitis B M08780 Ab (N=241,40)	0.8	92.5
Meningitis B M09910 Ab (N=256,43)	1.2	93
Meningitis B M08320 Ab (N=277,45)	45.1	86.8
Meningitis B M14879 Ab (N=252,47)	3.3	23.2
Meningitis B M09345 Ab (N=263,48)	32.3	74.9
Meningitis B M14594 Ab (N=254,44)	35.8	97.7
Meningitis B M07621 Ab (N=259,40)	0.4	77.5
Meningitis B M13568 Ab (N=268,40)	9.7	95
Meningitis B M18017 Ab (N=262,31)	0	96.8
Meningitis B M08420 Ab (N=260,40)	0.8	95
Meningitis B M07959 Ab (N=243,35)	1.2	97.1
Meningitis B M06970 Ab (N=243,32)	28.8	90.6
Meningitis B M10491 Ab (N=254,39)	16.1	82.1
Meningitis B M13569 Ab (N=233,31)	0.4	96.8
Meningitis B M10182 Ab (N=251,44)	0	0
Meningitis B M13547 Ab (N=260,44)	5	47.7
Meningitis B M15276 Ab (N=238,41)	0.4	87.8

No statistical analyses for this end point

Secondary: Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination schedule for the MenB_0_2_6 group [3 dose], MenB_0_6 group and last MenABCWY dose (pooled lots)

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End point title

Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination schedule for the MenB_0_2_6 group [3 dose], MenB_0_6 group and last MenABCWY dose (pooled lots) ^[45]

End point description

The percentage of participants classified by percentage of N.meningitidis serogroup B invasive strains killed using enc-hSBA and the corresponding 2- sided 95% CI based on Clopper-Pearson method is calculated for each vaccine group. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (Day 211 for MenB_0_2_6 group (3 dose schedule), MenB_0_6 group and ABCWY_Pooled group)

Notes
[45] - 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: As specified in the Protocol, the analysis assesses the percentage of serogroup B invasive disease strains killed within a subject using enc-hSBA of the rMenB+OMV and MenABCWY vaccines.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled
Number of subjects analysed	790	813	817
Units: Percentage of participants
number (confidence interval 95%)
>=50% killed strains	98.7 (97.7 to 99.4)	98.5 (97.4 to 99.2)	98 (96.8 to 98.9)
>=55% killed strains	98.4 (97.2 to 99.1)	97.4 (96.1 to 98.4)	96.8 (95.4 to 97.9)
>=60% killed strains	97.8 (96.6 to 98.7)	96.8 (95.3 to 97.9)	95.2 (93.5 to 96.6)
>=65% killed strains	96.5 (94.9 to 97.6)	93.6 (91.7 to 95.2)	90.1 (87.8 to 92)
>=70% killed strains	93.4 (91.5 to 95)	89.8 (87.5 to 91.8)	84.1 (81.4 to 86.5)
>=75% killed strains	86.8 (84.3 to 89.1)	82.2 (79.4 to 84.7)	74.7 (71.5 to 77.6)
>=80% killed strains	79.2 (76.2 to 82)	75.5 (72.4 to 78.4)	66 (62.6 to 69.2)
>=85% killed strains	62.8 (59.3 to 66.2)	60.4 (56.9 to 63.8)	50.1 (46.6 to 53.5)
>=90% killed strains	43.7 (40.2 to 47.2)	41.3 (37.9 to 44.8)	32.1 (28.9 to 35.4)
>=95% killed strains	22.5 (19.7 to 25.6)	21 (18.3 to 24)	13.7 (11.4 to 16.3)
100% killed strains	10 (8 to 12.3)	8.4 (6.6 to 10.5)	6.1 (4.6 to 8)

No statistical analyses for this end point

Secondary: Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

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End point title

Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination with rMenB+OMV NZ (0,2-months) ^[46]

End point description

The percentage of participants are classified by percentage of N.meningitidis serogroup B invasive strains killed using enc-hSBA and the corresponding 2- sided 95% CI based on Clopper-Pearson method is calculated for each vaccine group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (Day 91 for MenB_0_2_6 group [2 dose schedule])

Notes
[46] - 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: As specified in the Protocol, the analysis assesses the percentage of serogroup B invasive disease strains killed within a subject using enc-hSBA of the rMenB+OMV vaccine.

End point values	MenB_0_2_6 Group
Number of subjects analysed	831
Units: Percentage of participants
number (confidence interval 95%)
>=50% killed strains	98.6 (97.5 to 99.3)
>=55% killed strains	97.7 (96.5 to 98.6)
>=60% killed strains	96.5 (95 to 97.7)
>=65% killed strains	92.2 (90.1 to 93.9)
>=70% killed strains	84.8 (82.2 to 87.2)
>=75% killed strains	75.7 (72.6 to 78.6)
>=80% killed strains	66.7 (63.3 to 69.9)
>=85% killed strains	49.7 (46.2 to 53.2)
>=90% killed strains	33.8 (30.6 to 37.1)
>=95% killed strains	16.2 (13.8 to 18.9)
100% killed strains	7.7 (6 to 9.7)

No statistical analyses for this end point

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

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End point title

Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots) ^[47]

End point description

The immune response to rMenB+OMV NZ and MenABCWY vaccine is evaluated by measuring bactericidal activity against each (individual response) and all (composite response) N. meningitidis serogroup B indicator strains(M14459, 96217, M13520 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively). As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At Day 1 (pre-vaccination) and1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group and ABCWY_Pooled group)

Notes
[47] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV and MenABCWY vaccines against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled
Number of subjects analysed	749	731	780
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459) Ab, Day 1 (N=749,730,762)	4.9 (3.5 to 6.7)	3.4 (2.2 to 5)	5.4 (3.9 to 7.2)
fHbp (M14459) Ab, Day 211 (N=690,707,738)	97.4 (95.9 to 98.4)	94.6 (92.7 to 96.2)	95.9 (94.2 to 97.2)
NadA (96217) Ab, Day 1 (N=744,731,780)	6.2 (4.6 to 8.2)	4.4 (3.0 to 6.1)	6.2 (4.6 to 8.1)
NadA (96217) Ab, Day 211 (N=691,707,734)	100 (99.5 to 100)	98 (96.7 to 98.9)	96.2 (94.5 to 97.5)
NHBA (M13520) Ab, Day 1 (N=749,731,764)	23.2 (20.3 to 26.4)	20.9 (18 to 24.1)	18.5 (15.8 to 21.4)
NHBA (M13520) Ab, Day 211 (N=695,711,738)	97.0 (95.4 to 98.1)	97.5 (96.0 to 98.5)	95.3 (93.5 to 96.7)
PorA (NZ98/254) Ab, Day 1 (N=738,716,751)	2.3 (1.3 to 3.7)	1.4 (0.7 to 2.6)	2.1 (1.2 to 3.4)
PorA (NZ98/254) Ab, Day 211 (N=657,684,709)	85.8 (82.9 to 88.4)	82.6 (79.5 to 85.4)	75.3 (72.0 to 78.5)
Composite Response, Day=1 (N=727,708,747)	1.1 (0.5 to 2.2)	0.6 (0.2 to 1.4)	1.1 (0.5 to 2.1)
Composite Response, Day=211 (N=654,683,707)	83.3 (80.3 to 86.1)	80.7 (77.5 to 83.6)	71.4 (67.9 to 74.7)

No statistical analyses for this end point

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

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End point title

Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months) ^[48]

End point description

The immune response to rMenB+OMV NZ is evaluated by measuring bactericidal activity against each (individual response) and all (composite response) N. meningitidis serogroup B indicator strains (M14459, 96217, M13520 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively). Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At Day 1 (pre-vaccination) and1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 group [2 dose schedule])

Notes
[48] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV vaccine against N. meningitidis serogroup B indicator strain.

End point values	MenB_0_2_6 Group
Number of subjects analysed	753
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459) Ab, Day 1 (N=749)	4.9 (3.5 to 6.7)
fHbp (M14459) Ab, Day 91 (N=750)	92.9 (90.9 to 94.7)
NadA (96217) Ab, Day 1 (N=744)	6.2 (4.6 to 8.2)
NadA (96217) Ab, Day 91 (N=753)	99.5 (98.6 to 99.9)
NHBA (M13520) Ab, Day 1 (N=749)	23.2 (20.3 to 26.4)
NHBA (M13520) Ab, Day 91 (N=750)	96.1 (94.5 to 97.4)
PorA N (NZ98/254) Ab, Day 1 (N=738)	2.3 (1.3 to 3.7)
PorA N (NZ98/254) Ab, Day 91 (N=745)	80 (76.9 to 82.8)
Composite Response, Day=1 (N=727)	1.1 (0.5 to 2.2)
Composite Response, Day=91 (N=744)	75.5 (72.3 to 78.6)

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

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End point title

Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots) ^[49]

End point description

The immune response to 3 dose (0,2,6-M), 2 dose (0,6-M) schedule of rMenB+OMV NZ and 2 doses of MenABCWY vaccine was evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains- M14459, 96217, NZ98/254 and M13520 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively compared to baseline. Four-fold rise per each indicator strain was defined as a post-vaccination hSBA titre ≥16 for subjects with a pre-vaccination hSBA titre <4 a post-vaccination hSBA titer ≥4 times the LLOQ for subjects with a pre-vaccination hSBA titre ≥LOD and <LLOQ a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for participants with a pre-vaccination hSBA titre ≥ LLOQ. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group [3 dose schedule], MenB_0_6 group and ABCWY_Pooled group) compared to Day 1 (baseline)

Notes
[49] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV and MenABCWY vaccines against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled
Number of subjects analysed	685	704	731 ^[50]
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459) Ab (N=679,699, 729)	86.7 (84.0 to 89.2)	82.4 (79.4 to 85.2)	78.9 (75.7 to 81.8)
NadA (96217) Ab (N=679,700,725)	98.7 (97.5 to 99.4)	95.3 (93.4 to 96.7)	92.3 (90.1 to 94.1)
NHBA (M13520) Ab (N=685,704,731)	66.9 (63.2 to 70.4)	69.5 (65.9 to 72.8)	61.1 (57.5 to 64.7)
PorA (NZ98/254) Ab (N=637,664,693)	56.5 (52.6 to 60.4)	57.2 (53.4 to 61.0)	42.4 (38.7 to 46.2)

Notes
[50] - Analysis of final results for the ABCWY group is ongoing and will be updated subsequently.

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2 months)

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End point title

Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2 months) ^[51]

End point description

The immune response to 2 dose (0,2-M) is evaluated by measuring bactericidal activity against each of the N. meningitidis serogroup B test strains- M14459, 96217, NZ98/254 and M13520 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively compared to baseline. Four-fold rise per each indicator strain was defined as a post-vaccination hSBA titre ≥16 for participants with a pre-vaccination hSBA titre <4 a post-vaccination hSBA titre ≥4 times the LLOQ for subjects with a pre-vaccination hSBA titre ≥LOD and <LLOQ a post-vaccination hSBA titre ≥4 times the pre-vaccination hSBA titre for subjects with a pre-vaccination hSBA titre ≥ LLOQ. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 [2-dose schedule]) compared to Day 1 (baseline)

Notes
[51] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV vaccines against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group
Number of subjects analysed	739
Units: Percentage of participants
number (confidence interval 95%)
fHbp (M14459) Ab (N=739)	74.6 (71.3 to 77.7)
NadA (96217) Ab (N=738)	96.3 (94.7 to 97.6)
NHBA (M13520) Ab (N=739)	58.5 (54.8 to 62.0)
PorA (NZ98/254) Ab (N=724)	53.5 (49.7 to 57.1)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titres (GMTs) against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

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End point title

hSBA Geometric Mean Titres (GMTs) against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots) ^[52]

End point description

The immune response to rMenB+OMV NZ and MenABCWY vaccine was evaluated by measuring bactericidal activity against N. meningitidis serogroup B test strains in terms of GMTs after vaccination compared to baseline (Day 1). For each N. meningitidis serogroup B test strain (M14459, M13520, 96217 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively), The GMTs (After vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At Day 1 (pre-vaccination) and at 1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group (3 dose schedule), MenB_0_6 group and ABCWY_Pooled group)

Notes
[52] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV and MenABCWY vaccines against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled
Number of subjects analysed	749	731	780
Units: Titers
geometric mean (confidence interval 95%)
fHbp (M14459) Ab, Day 1 (N=749,730,762)	2.8 (2.7 to 2.8)	2.7 (2.6 to 2.8)	2.8 (2.7 to 2.9)
fHbp (M14459) Ab, Day 211 (N=690,707,738)	30.8 (28.3 to 33.5)	28.1 (25.9 to 30.6)	25 (23 to 27.1)
NadA (96217) Ab, Day 1 (N=744,731,780)	8.4 (8.1 to 8.6)	8.3 (8 to 8.6)	8.5 (8.2 to 8.8)
NadA (96217) Ab, Day 211 (N=691,707,734)	267.2 (243.7 to 293)	215.1 (196.2 to 235.9)	150.6 (137.3 to 165.2)
NHBA (M13520) Ab, Day 1 (N=749,731,764)	3.4 (3.1 to 3.7)	3.2 (3 to 3.5)	3.1 (2.8 to 3.4)
NHBA (M13520) Ab, Day 211 (N=695,711,738)	30.6 (27.7 to 33.7)	33.2 (30.2 to 36.6)	25.2 (22.9 to 27.8)
PorA (NZ98/254) Ab, Day 1 (N=738,716,751)	3.2 (3.1 to 3.2)	3.1 (3 to 3.2)	3.1 (3.1 to 3.2)
PorA (NZ98/254) Ab, Day 211 (N=657,684,709)	18.1 (16.3 to 20.1)	17.7 (15.9 to 19.6)	12.9 (11.6 to 14.4)

No statistical analyses for this end point

Secondary: hSBA GMTs against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

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End point title

hSBA GMTs against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months) ^[53]

End point description

End point type

Secondary

End point timeframe

At Day 1 (pre-vaccination) and at 1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 group [2-dose schedule])

Notes
[53] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV vaccine against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group
Number of subjects analysed	753
Units: Titers
geometric mean (confidence interval 95%)
fHbp (M14459) Ab, Day 1(N=749)	2.8 (2.7 to 2.8)
fHbp (M14459) Ab, Day 91(N=750)	20.9 (18.9 to 23.1)
NadA (96217) Ab, Day 1(N=744)	8.4 (8.1 to 8.6)
NadA (96217) Ab, Day 91(N=753)	178.5 (161.7 to 197.2)
NHBA (M13520) Ab, Day 1(N=749)	3.4 (3.1 to 3.7)
NHBA (M13520) Ab, Day 91(N=750)	27.2 (24.1 to 30.6)
PorA (NZ98/254) Ab, Day 1(N=738)	3.2 (3.1 to 3.2)
PorA (NZ98/254) Ab, Day 91(N=745)	17.1 (15.2 to 19.3)

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Ratios (GMRs) for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

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End point title

hSBA Geometric Mean Ratios (GMRs) for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots) ^[54]

End point description

The immune response to rMenB+OMV NZ vaccine was evaluated by measuring bactericidal activity against N. meningitidis serogroup B test strains after vaccination compared to baseline (Day 1). For each N. meningitidis serogroup B test strain (M14459, M13520, 96217 and NZ98/254 for fHbp, NadA, NHBA and PorA P1.4 antigens, respectively), the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the MenB_0_2_6 group, MenB_0_6 group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 211 for MenB_0_2_6 group (3 dose schedule), MenB_0_6 group and ABCWY_Pooled group) compared to Day 1 (baseline)

Notes
[54] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV and MenABCWY vaccines against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group	MenB_0_6 Group	ABCWY_Pooled
Number of subjects analysed	685	704	731
Units: Ratio
geometric mean (confidence interval 95%)
fHbp (M14459) Ab (N=679,699,729)	11.2 (10.3 to 12.2)	10.5 (9.6 to 11.4)	9 (8.2 to 9.8)
NadA (96217) Ab (N=679,700,725)	32.1 (29.1 to 35.3)	25.8 (23.5 to 28.4)	17.7 (16 to 19.4)
NHBA (M13520) Ab (N=685,704,731)	9.1 (8.2 to 10.1)	10.6 (9.5 to 11.7)	8.2 (7.4 to 9.1)
PorA (NZ98/254) Ab (N=637,664,693)	5.8 (5.2 to 6.5)	5.8 (5.2 to 6.4)	4.1 (3.7 to 4.6)

No statistical analyses for this end point

Secondary: hSBA GMRs for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

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End point title

hSBA GMRs for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2-months) ^[55]

End point description

End point type

Secondary

End point timeframe

At 1 month after the vaccination schedule (i.e., Day 91 for MenB_0_2_6 group [2-dose schedule]) compared to Day 1 (baseline)

Notes
[55] - 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: As specified in the Protocol, the analysis assesses the immune response of the rMenB+OMV vaccines against N. meningitidis serogroup B indicator strains.

End point values	MenB_0_2_6 Group
Number of subjects analysed	739
Units: Ratio
geometric mean (confidence interval 95%)
fHbp (M14459) Ab (N=739)	7.7 (6.9 to 8.5)
NadA (96217) Ab (N=738)	21.7 (19.5 to 24)
NHBA (M13520) Ab (N=739)	8 (7.1 to 9)
PorA (NZ98/254) Ab (N=724)	5.5 (4.9 to 6.2)

No statistical analyses for this end point

Secondary: Percentage of participants with hSBA titers >= LLOQ for each of the N. meningitidis serogroups A,C,W,Y at Day 1 and at 1 month after the first and the last MenABCWY vaccination for ABCWY_Pooled group and 1 month after the MenACWY vaccine for ACWY group

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End point title

Percentage of participants with hSBA titers >= LLOQ for each of the N. meningitidis serogroups A,C,W,Y at Day 1 and at 1 month after the first and the last MenABCWY vaccination for ABCWY_Pooled group and 1 month after the MenACWY vaccine for ACWY group ^[56]

End point description

The immune responses to MenABCWY and MenACWY vaccines were evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y after vaccination compared to baseline (Day 1) and expressed as the percentage of participants with hSBA titers >= LLOQ for serogroups A, C, W and Y at baseline and 1 month after vaccination schedule of MenABCWY and MenACWY vaccines. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At Day 1, and 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots – second dose])

Notes
[56] - 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: As specified in the Protocol, the analysis assesses the immune response of the MenABCWY and MenACWY vaccines against N. meningitidis serogroups A, C, W, and Y.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	1489	141
Units: Percentage of participants
number (confidence interval 95%)
Men A, Day 1 (N=1452, 137)	9.2 (7.7 to 10.8)	11.7 (6.8 to 18.3)
Men A, Day 31 (N=132, 133)	79.5 (71.7 to 86.1)	90.2 (83.9 to 94.7)
Men A, Day 211 (N=1446)	98.6 (97.9 to 99.2)	99999 (99999 to 99999)
Men C, Day 1 (N=1487, 139)	29.8 (27.5 to 32.2)	28.8 (21.4 to 37.1)
Men C, Day 31 (N=139,136)	74.8 (66.8 to 81.8)	64.0 (55.3 to 72.0)
Men C, Day 211 (N=1457)	99.6 (99.1 to 99.8)	99999 (99999 to 99999)
Men W, Day 1 (N=1473,140)	12.6 (10.9 to 14.4)	12.9 (7.8 to 19.6)
Men W, Day 31 (N=142,137)	80.3 (72.8 to 86.5)	69.3 (60.9 to 76.9)
Men W, Day 211 (N=1463)	99.2 (98.7 to 99.6)	99999 (99999 to 99999)
Men Y, Day 1 (N=1489,141)	12.2 (10.6 to 14.0)	13.5 (8.3 to 20.2)
Men Y, Day 91 (N=146,140)	82.2 (75.0 to 88.0)	80.0 (72.4 to 86.3)
Men Y, Day 211 (N=1461)	99.2 (98.7 to 99.6)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first MenABCWY dose for ABCWY_Pooled group compared to the MenACWY vaccine for ACWY group relative to baseline (Day 1)

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End point title

Percentage of participants with 4-fold rise in hSBA titers for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first MenABCWY dose for ABCWY_Pooled group compared to the MenACWY vaccine for ACWY group relative to baseline (Day 1) ^[57]

End point description

The immune response to MenABCWY vaccine compared to MenACWY vaccine was evaluated by measuring bactericidal activity against each of the N. meningitidis serogroups A, C, W and Y at Day 31 compared to baseline (Day 1). Four-fold rise is defined as: - If the pre-vaccination hSBA titer is < 4, then post-vaccination hSBA titer should be ≥ 16. - If the pre-vaccination hSBA titer is ≥ LOD but < LLOQ, then post-vaccination hSBA titer should be ≥ 4 times the LLOQ. - If the pre-vaccination hSBA titer is ≥ LLOQ, then post-vaccination hSBA titer should be ≥ 4 times the pre-vaccination hSBA titer. The corresponding 2- sided 95% CI based on Clopper-Pearson method is calculated for each vaccine group. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled group] and for ACWY Group) relative to baseline (Day 1)

Notes
[57] - 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: As specified in the Protocol, the analysis assesses the effectiveness of the rMenB+OMV vaccine compared to one dose of MenACWY vaccination in the ACWY group.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	146	140
Units: Percentage of participants
number (confidence interval 95%)
Men A (N=127,129)	74.0 (65.5 to 81.4)	86.0 (78.8 to 91.5)
Men C (N=139,134)	66.9 (58.4 to 74.6)	56.7 (47.9 to 65.2)
Men W (N=139,136)	74.1 (66.0 to 81.2)	66.2 (57.6 to 74.1)
Men Y (N=146,140)	76.0 (68.3 to 82.7)	72.1 (63.9 to 79.4)

No statistical analyses for this end point

Secondary: hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and the last MenABCWY vaccination for the ABCWY_Pooled group and at 1 month after the MenACWY vaccination for ACWY Group

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End point title

hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and the last MenABCWY vaccination for the ABCWY_Pooled group and at 1 month after the MenACWY vaccination for ACWY Group ^[58]

End point description

The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y in terms of GMTs after vaccination compared to baseline (Day 1). For each N. meningitidis serogroups A, C, W and Y, the GMTs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At Day 1, and 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots – second dose])

Notes
[58] - 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: As specified in the Protocol, the analysis assesses the immune response of the MenABCWY and MenACWY vaccines against N. meningitidis serogroups A, C, W, and Y.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	1489	141
Units: Titers
geometric mean (confidence interval 95%)
Men A, Day 1 (N=1452,137)	11.1 (10.3 to 11.9)	12.7 (10.9 to 14.8)
Men A, Day 31 (N=132,133)	175.3 (121.2 to 253.3)	474.8 (331.3 to 680.3)
Men A, Day 211 (N=1446)	352.0 (322.0 to 384.7)	99999 (99999 to 99999)
Men C, Day 1 (N=1487,139)	12.0 (10.9 to 13.3)	11.4 (9.1 to 14.3)
Men C, Day 31 (N=139,136)	674.8 (355.9 to 1279.4)	379.0 (204.4 to 703.0)
Men C, Day 211 (N=1457)	1162.5 (1015.7 to 1330.5)	99999 (99999 to 99999)
Men W, Day 1 (N=1473,140)	8.0 (7.4 to 8.7)	7.4 (6.2 to 8.9)
Men W, Day 31 (N=142,137)	374.0 (243.4 to 574.8)	194.3 (128.3 to 294.2)
Men W, Day 211 (N=1463)	666.5 (603.2 to 736.3)	99999 (99999 to 99999)
Men Y, Day 1 (N=1489,141)	9.3 (8.7 to 10.0)	9.9 (8.6 to 11.5)
Men Y, Day 31 (N=146,140)	375.4 (246.9 to 570.7)	320.9 (213.8 to 481.7)
Men Y, Day 211 (N=1461)	655.9 (587.0 to 733.0)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: GMRs for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first and the last MenABCWY vaccination for the ABCWY _Pooled group and at 1 month after the MenACWY vaccination for ACWY Group

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End point title

GMRs for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first and the last MenABCWY vaccination for the ABCWY _Pooled group and at 1 month after the MenACWY vaccination for ACWY Group ^[59]

End point description

The immune responses to MenABCWY and MenACWY vaccines are evaluated by measuring bactericidal activity against N. meningitidis serogroups A, C, W and Y. For each N. meningitidis serogroups A, C, W and Y, the GMRs (after vaccination/baseline) are calculated, with their associated 2-sided 95% CIs. As pre-specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots – second dose]) compared to baseline (Day 1)

Notes
[59] - 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: As specified in the Protocol, the analysis assesses the immune response of the MenABCWY and MenACWY against N. meningitidis serogroups A, C, W, and Y.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	1446	140
Units: Ratio
geometric mean (confidence interval 95%)
Men A, Day 31 (N=127,129)	11.8 (7.9 to 17.7)	31.8 (21.4 to 47.1)
Men A, Day 211 (N=1397)	31.2 (28.3 to 34.5)	99999 (99999 to 99999)
Men C, Day 31 (N=139,134)	30.9 (16.9 to 56.2)	22.9 (12.8 to 41.1)
Men C, Day 211 (N=1439)	96.9 (84.5 to 111.1)	99999 (99999 to 99999)
Men W, Day 31 (N=139,136)	32.9 (21.7 to 50.0)	23.2 (15.5 to 34.7)
Men W, Day 211 (N=1432)	83.8 (74.9 to 93.8)	99999 (99999 to 99999)
Men Y, Day 31 (N=146,140)	28.1 (18.3 to 43.2)	25.6 (16.9 to 38.8)
Men Y, Day 211 (N=1446)	70.2 (62.3 to 79.1)	99999 (99999 to 99999)

No statistical analyses for this end point

Secondary: Total Immunoglobulin G (IgG) antibodies concentrations against N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and the last MenABCWY vaccination for ABCWY _Pooled group and 1 month after the MenACWY vaccination for ACWY Group

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End point title

Total Immunoglobulin G (IgG) antibodies concentrations against N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and the last MenABCWY vaccination for ABCWY _Pooled group and 1 month after the MenACWY vaccination for ACWY Group ^[60]

End point description

The immune responses to MenABCWY and MenACWY vaccines were evaluated by measuring the total lgG in terms of electrochemiluminescence-based multiplex (EGL) geometric mean concentrations (GMCs) which was an alternative assay to Enzyme-Linked lmmunosorbent Assay (ELISA). EGL (validated assay) was used because ELISA is not validated. As pre- specified in the protocol, data reported in this outcome measure were presented for the ACWY group and ABCWY pooled group, participants from the ABCWY-1, ABCWY-2, and ABCWY-3 groups were pooled into a single group. Analysis was performed on the FAS.

End point type

Secondary

End point timeframe

At Day 1, and 1 month after vaccination schedule (i.e, at Day 31 for ABCWY group [pooled lots -first dose] and for ACWY Group, and at Day 211 for ABCWY group [pooled lots - second dose])

Notes
[60] - 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: As specified in the Protocol, the analysis assesses the immune response of the MenABCWY and MenACWY vaccines against N. meningitidis serogroups A, C, W, and Y.

End point values	ABCWY_Pooled	ACWY Group
Number of subjects analysed	179	172
Units: microgram per milliliter(µg/mL)
geometric mean (confidence interval 95%)
Men A, Day 1 (N=170, 179)	1.9 (1.6 to 2.2)	2.3 (2.0 to 2.7)
Men A, Day 31 (N=168, 177)	18.1 (13.8 to 23.8)	53.7 (40.8 to 70.7)
Men A, Day 211 (N=164)	30.2 (23.3 to 39.2)	99999 (99999 to 99999)
Men C, Day 1 (N=170, 179)	0.7 (0.6 to 0.8)	0.8 (0.7 to 1.0)
Men C, Day 31 (N=170, 175)	15.5 (11.6 to 20.7)	13.8 (10.4 to 18.4)
Men C, Day 211 (N=163)	17.0 (13.1 to 22.0)	99999 (99999 to 99999)
Men W, Day 1 (N=170, 179)	0.5 (0.4 to 0.6)	0.6 (0.5 to 0.7)
Men W, Day 31 (N=172, 178)	9.1 (6.5 to 12.8)	8.4 (6.0 to 11.6)
Men W, Day 211 (N=164)	21.7 (16.0 to 29.5)	99999 (99999 to 99999)
Men Y, Day 1 (N=170, 179)	0.9 (0.7 to 1.0)	0.9 (0.8 to 1.0)
Men Y, Day 31 (N=172, 178)	12.9 (9.2 to 18.0)	14.3 (10.2 to 19.8)
Men Y, Day 211 (N=164)	26.3 (19.6 to 35.4)	99999 (99999 to 99999)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs and Non-serious AEs (Other AEs) were collected through the entire period of the study (from Day 1 up to study end [Day 361])

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

MenB_0_2_6 Group

Reporting group description

Participants received 3 doses of rMenB+OMV NZ vaccine on Day 1, Day 61 and Day 181. Participants received 1 dose of MenACWY vaccine at Day 211 as a standard of care.

Reporting group title

ABCWY_Pooled

Reporting group description

Reporting group title

ACWY Group

Reporting group description

Reporting group title

MenB_0_6 Group

Reporting group description

Participants received 2 doses of rMenB+OMV NZ vaccine on Day 1, and Day 181, 1 dose of MenACWY vaccine on Day 61. Participants received 1 dose of Placebo on Day 211 to maintain blinding.

Serious adverse events	MenB_0_2_6 Group	ABCWY_Pooled	ACWY Group	MenB_0_6 Group
Total subjects affected by serious adverse events
subjects affected / exposed	20 / 897 (2.23%)	25 / 1657 (1.51%)	5 / 178 (2.81%)	22 / 906 (2.43%)
number of deaths (all causes)	1	0	0	1
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Testis cancer
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (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
Brain stem glioma
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Ovarian fibroma
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Vascular disorders
Haematoma
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Complication of pregnancy
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Placental insufficiency
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Pre-eclampsia
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (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
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Reproductive system and breast disorders
Ovarian cyst ruptured
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Substance-induced psychotic disorder
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Major depression
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Depression suicidal
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Mental disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Anorexia nervosa
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Suicidal ideation
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Psychotic disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Thinking abnormal
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Investigations
Troponin T increased
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (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
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	3 / 897 (0.33%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Subdural haemorrhage
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Skin laceration
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Road traffic accident
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Poisoning
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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 / 1
Lower limb fracture
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Intentional overdose
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Ulna fracture
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Traumatic liver injury
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Injury
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Back injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Neck injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Head injury
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain contusion
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Skull fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Tibia fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Congenital, familial and genetic disorders
Urachal abnormality
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Nervous system disorders
Dysarthria
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (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
Dizziness
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (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
Aphasia
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Paresis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Petit mal epilepsy
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Speech disorder
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (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
Subarachnoid haemorrhage
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Neuromyelitis optica spectrum disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Eye disorders
Hypermetropia
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Colitis ulcerative
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Vomiting
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Hepatitis toxic
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Skin and subcutaneous tissue disorders
Excessive granulation tissue
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Vancomycin infusion reaction
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Urethral stenosis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Gastroenteritis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Peritonsillar abscess
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
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
Sepsis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tooth abscess
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (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
Post-acute COVID-19 syndrome
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Pharyngeal abscess
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Infected dermal cyst
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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
Metabolism and nutrition disorders
Type 1 diabetes mellitus
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (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

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

Non-serious adverse events	MenB_0_2_6 Group	ABCWY_Pooled	ACWY Group	MenB_0_6 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	876 / 897 (97.66%)	1599 / 1657 (96.50%)	173 / 178 (97.19%)	872 / 906 (96.25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Skin papilloma
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	1	0	2
Benign soft tissue neoplasm
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Fibroadenoma of breast
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Lipoma
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Melanocytic naevus
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Vascular disorders
Pallor
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Hypertension
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	1	0	2
Haematoma
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	1	1	0
Hot flush
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Varicose vein
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Hypotension
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hyperaemia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Peripheral venous disease
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Orthostatic hypotension
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Induration
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Administration site erythema
subjects affected / exposed	209 / 897 (23.30%)	321 / 1657 (19.37%)	21 / 178 (11.80%)	157 / 906 (17.33%)
occurrences all number	300	397	24	203
Administration site induration
subjects affected / exposed	138 / 897 (15.38%)	223 / 1657 (13.46%)	17 / 178 (9.55%)	113 / 906 (12.47%)
occurrences all number	180	273	19	142
Administration site pain
subjects affected / exposed	851 / 897 (94.87%)	1561 / 1657 (94.21%)	149 / 178 (83.71%)	853 / 906 (94.15%)
occurrences all number	2229	3056	240	1768
Administration site swelling
subjects affected / exposed	202 / 897 (22.52%)	305 / 1657 (18.41%)	22 / 178 (12.36%)	158 / 906 (17.44%)
occurrences all number	293	401	25	200
Asthenia
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Chest pain
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	0	3	1	2
Chills
subjects affected / exposed	8 / 897 (0.89%)	6 / 1657 (0.36%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	8	6	0	4
Cyst
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Fatigue
subjects affected / exposed	604 / 897 (67.34%)	1066 / 1657 (64.33%)	105 / 178 (58.99%)	579 / 906 (63.91%)
occurrences all number	1183	1807	174	1005
Feeling hot
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	1 / 178 (0.56%)	1 / 906 (0.11%)
occurrences all number	0	3	1	1
Influenza like illness
subjects affected / exposed	2 / 897 (0.22%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	2	2	0	3
Thirst
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Injection site haematoma
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Injection site hypoaesthesia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Injection site induration
subjects affected / exposed	8 / 897 (0.89%)	13 / 1657 (0.78%)	2 / 178 (1.12%)	5 / 906 (0.55%)
occurrences all number	11	14	2	5
Injection site mass
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	3	0	2
Injection site pain
subjects affected / exposed	3 / 897 (0.33%)	13 / 1657 (0.78%)	1 / 178 (0.56%)	8 / 906 (0.88%)
occurrences all number	3	13	1	8
Injection site pruritus
subjects affected / exposed	2 / 897 (0.22%)	5 / 1657 (0.30%)	1 / 178 (0.56%)	1 / 906 (0.11%)
occurrences all number	4	6	1	2
Injection site rash
subjects affected / exposed	1 / 897 (0.11%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	4	0	2
Injection site swelling
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Injection site warmth
subjects affected / exposed	2 / 897 (0.22%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	3	3	0	1
Malaise
subjects affected / exposed	4 / 897 (0.45%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	5	3	0	3
Non-cardiac chest pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	1	1	0
Pain
subjects affected / exposed	4 / 897 (0.45%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	5	4	0	2
Peripheral swelling
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	1	1	0
Pyrexia
subjects affected / exposed	66 / 897 (7.36%)	115 / 1657 (6.94%)	7 / 178 (3.93%)	59 / 906 (6.51%)
occurrences all number	69	122	7	62
Swelling
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Injection site bruising
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Vaccination site pain
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Vaccination site urticaria
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Vaccination site warmth
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Vessel puncture site pain
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	0	0	2
Vaccination site pruritus
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Medical device pain
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Axillary pain
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Chest discomfort
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Discomfort
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Feeling cold
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injection site discomfort
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injection site eczema
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injection site erythema
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injection site haemorrhage
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injection site papule
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injection site paraesthesia
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Injection site reaction
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Oedema peripheral
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Vaccination site bruising
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Vaccination site erythema
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Vaccination site reaction
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Swelling face
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Immune system disorders
Anaphylactoid reaction
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Drug hypersensitivity
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Food allergy
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	2	1	0	1
Hypersensitivity
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Multiple allergies
subjects affected / exposed	2 / 897 (0.22%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	2	0	0	1
Seasonal allergy
subjects affected / exposed	7 / 897 (0.78%)	9 / 1657 (0.54%)	2 / 178 (1.12%)	7 / 906 (0.77%)
occurrences all number	7	9	2	7
Allergy to animal
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Allergy to arthropod sting
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Dust allergy
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Social circumstances
Menarche
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Reproductive system and breast disorders
Heavy menstrual bleeding
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Breast cyst
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Breast inflammation
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Breast mass
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Breast tenderness
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Dysmenorrhoea
subjects affected / exposed	14 / 897 (1.56%)	25 / 1657 (1.51%)	6 / 178 (3.37%)	10 / 906 (1.10%)
occurrences all number	19	31	6	10
Endometriosis
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Intermenstrual bleeding
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Nipple enlargement
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Ovarian cyst
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Penile rash
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Premenstrual syndrome
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Testicular pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Vaginal haemorrhage
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Menstruation irregular
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Abnormal uterine bleeding
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Amenorrhoea
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Bartholin's cyst
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Breast discharge
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Breast haematoma
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Breast pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Menstruation delayed
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Premenstrual pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Uterine spasm
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	4 / 897 (0.45%)	8 / 1657 (0.48%)	2 / 178 (1.12%)	1 / 906 (0.11%)
occurrences all number	4	8	2	1
Asthma
subjects affected / exposed	4 / 897 (0.45%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	6 / 906 (0.66%)
occurrences all number	5	2	0	8
Cough
subjects affected / exposed	4 / 897 (0.45%)	16 / 1657 (0.97%)	3 / 178 (1.69%)	3 / 906 (0.33%)
occurrences all number	4	16	3	4
Dyspnoea
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Epistaxis
subjects affected / exposed	1 / 897 (0.11%)	4 / 1657 (0.24%)	1 / 178 (0.56%)	3 / 906 (0.33%)
occurrences all number	1	4	1	3
Nasal congestion
subjects affected / exposed	12 / 897 (1.34%)	16 / 1657 (0.97%)	0 / 178 (0.00%)	6 / 906 (0.66%)
occurrences all number	13	18	0	6
Oropharyngeal pain
subjects affected / exposed	12 / 897 (1.34%)	29 / 1657 (1.75%)	0 / 178 (0.00%)	11 / 906 (1.21%)
occurrences all number	12	29	0	12
Respiratory tract congestion
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Rhinalgia
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Rhinitis allergic
subjects affected / exposed	2 / 897 (0.22%)	3 / 1657 (0.18%)	1 / 178 (0.56%)	3 / 906 (0.33%)
occurrences all number	2	3	1	3
Sneezing
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Wheezing
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Tonsillolith
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Bronchial hyperreactivity
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Increased upper airway secretion
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Pleuritic pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Respiratory disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Throat clearing
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hiccups
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	6 / 897 (0.67%)	11 / 1657 (0.66%)	0 / 178 (0.00%)	8 / 906 (0.88%)
occurrences all number	6	11	0	8
Anorexia nervosa
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Aggression
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Adjustment disorder with depressed mood
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Adjustment disorder
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Attention deficit hyperactivity disorder
subjects affected / exposed	0 / 897 (0.00%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	0	4	0	4
Anxiety disorder
subjects affected / exposed	2 / 897 (0.22%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	5	0	0
Depression suicidal
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Disruptive mood dysregulation disorder
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Sleep disorder
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Panic attack
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	3	1	0	0
Depression
subjects affected / exposed	6 / 897 (0.67%)	14 / 1657 (0.84%)	2 / 178 (1.12%)	4 / 906 (0.44%)
occurrences all number	6	14	2	4
Confusional state
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Binge eating
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Insomnia
subjects affected / exposed	3 / 897 (0.33%)	7 / 1657 (0.42%)	1 / 178 (0.56%)	3 / 906 (0.33%)
occurrences all number	3	7	1	3
Stress
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Tic
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Suicidal ideation
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Anger
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Acute stress disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Irritability
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Mixed anxiety and depressive disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Obsessive-compulsive disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
School refusal
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hallucination
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Investigations
SARS-CoV-2 test positive
subjects affected / exposed	6 / 897 (0.67%)	6 / 1657 (0.36%)	1 / 178 (0.56%)	7 / 906 (0.77%)
occurrences all number	6	6	1	7
Body temperature increased
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Cardiac murmur
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Computerised tomogram abdomen abnormal
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Haemoglobin decreased
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Heart rate irregular
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Liver function test increased
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Serum ferritin decreased
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Streptococcus test positive
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Thyroid hormones decreased
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Blood pressure increased
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Heart rate increased
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Red blood cell count increased
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Weight decreased
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Arthropod bite
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	3	0	1
Arthropod sting
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Ankle fracture
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	3	0	1
Clavicle fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Ligament sprain
subjects affected / exposed	5 / 897 (0.56%)	14 / 1657 (0.84%)	1 / 178 (0.56%)	16 / 906 (1.77%)
occurrences all number	7	14	1	17
Contusion
subjects affected / exposed	3 / 897 (0.33%)	8 / 1657 (0.48%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	3	12	0	2
Eye abrasion
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Eye injury
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Facial bones fracture
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Fall
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	2 / 178 (1.12%)	2 / 906 (0.22%)
occurrences all number	1	3	2	2
Fibula fracture
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	0	0	1	2
Foot fracture
subjects affected / exposed	2 / 897 (0.22%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	5 / 906 (0.55%)
occurrences all number	2	5	0	6
Hand fracture
subjects affected / exposed	3 / 897 (0.33%)	6 / 1657 (0.36%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	3	7	0	1
Head injury
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	1	2	1	0
Human bite
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Humerus fracture
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Infusion related reaction
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Joint dislocation
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	1 / 178 (0.56%)	4 / 906 (0.44%)
occurrences all number	0	2	1	4
Joint injury
subjects affected / exposed	4 / 897 (0.45%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	4	4	0	3
Ligament rupture
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	1 / 178 (0.56%)	1 / 906 (0.11%)
occurrences all number	1	2	1	1
Concussion
subjects affected / exposed	3 / 897 (0.33%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	3	5	0	0
Limb injury
subjects affected / exposed	3 / 897 (0.33%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	5 / 906 (0.55%)
occurrences all number	3	5	0	5
Skin abrasion
subjects affected / exposed	3 / 897 (0.33%)	3 / 1657 (0.18%)	2 / 178 (1.12%)	2 / 906 (0.22%)
occurrences all number	3	3	2	3
Meniscus injury
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Muscle rupture
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	2	0	0
Muscle strain
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	3	0	1
Musculoskeletal foreign body
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Nail injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	1	0	2
Post procedural complication
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	1	0	2
Post-traumatic neck syndrome
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Procedural complication
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Procedural dizziness
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Procedural nausea
subjects affected / exposed	2 / 897 (0.22%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	2	0	0
Procedural pain
subjects affected / exposed	0 / 897 (0.00%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	4	0	1
Procedural vomiting
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Radius fracture
subjects affected / exposed	1 / 897 (0.11%)	4 / 1657 (0.24%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	1	4	1	2
Road traffic accident
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	1	0	2
Scratch
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Lower limb fracture
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Skin laceration
subjects affected / exposed	5 / 897 (0.56%)	5 / 1657 (0.30%)	1 / 178 (0.56%)	5 / 906 (0.55%)
occurrences all number	5	5	1	5
Thermal burn
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Tibia fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	1	1	0
Torus fracture
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Traumatic haematoma
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Ulna fracture
subjects affected / exposed	0 / 897 (0.00%)	4 / 1657 (0.24%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	4	1	0
Upper limb fracture
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	1	1	0	5
Vaccination complication
subjects affected / exposed	2 / 897 (0.22%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	3 / 906 (0.33%)
occurrences all number	2	0	1	3
Wrist fracture
subjects affected / exposed	2 / 897 (0.22%)	9 / 1657 (0.54%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	2	9	0	2
Tendon injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Anaesthetic complication
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Animal bite
subjects affected / exposed	0 / 897 (0.00%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	4	0	0
Animal scratch
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Tooth injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Bursa injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Compression fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Ear canal injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Foreign body in respiratory tract
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Ligament injury
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Limb crushing injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Limb fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Nasal injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Post procedural haemorrhage
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Soft tissue injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Sports injury
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Stress fracture
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Sunburn
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Bone contusion
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Traumatic haemorrhage
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Wound
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Congenital, familial and genetic disorders
Multiple endocrine neoplasia Type 1
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Rathke's cleft cyst
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Type V hyperlipidaemia
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Familial mediterranean fever
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Dermoid cyst
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Pectus excavatum
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 897 (0.00%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	4	0	1
Supraventricular tachycardia
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Tachycardia paroxysmal
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Tachycardia
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	3	0	0
Nervous system disorders
Dyskinesia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Dizziness
subjects affected / exposed	6 / 897 (0.67%)	7 / 1657 (0.42%)	1 / 178 (0.56%)	6 / 906 (0.66%)
occurrences all number	8	7	1	6
Headache
subjects affected / exposed	578 / 897 (64.44%)	929 / 1657 (56.07%)	97 / 178 (54.49%)	525 / 906 (57.95%)
occurrences all number	999	1578	148	874
Hypoaesthesia
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Taste disorder
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Syncope
subjects affected / exposed	1 / 897 (0.11%)	11 / 1657 (0.66%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	1	11	1	2
Speech disorder
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Somnolence
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	0	0	0
Lethargy
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	0	0	2
Migraine
subjects affected / exposed	3 / 897 (0.33%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	5 / 906 (0.55%)
occurrences all number	3	4	0	5
Myoclonus
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Neuromuscular blockade
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Presyncope
subjects affected / exposed	1 / 897 (0.11%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	5	0	1
Psychomotor hyperactivity
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Seizure
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Restless legs syndrome
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Carpal tunnel syndrome
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Neuralgia
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Paraesthesia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Sleep deficit
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Tension headache
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	4	0	1
Iron deficiency anaemia
subjects affected / exposed	4 / 897 (0.45%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	4	1	0	1
Lymphadenitis
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	2	1	0	1
Lymphadenopathy
subjects affected / exposed	5 / 897 (0.56%)	9 / 1657 (0.54%)	1 / 178 (0.56%)	7 / 906 (0.77%)
occurrences all number	6	9	1	7
Coagulopathy
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Increased tendency to bruise
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Ear and labyrinth disorders
Hypoacusis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Eustachian tube dysfunction
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Tympanic membrane perforation
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Vertigo
subjects affected / exposed	4 / 897 (0.45%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	4	2	0	3
Tinnitus
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Cerumen impaction
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	3	0	2
Ear discomfort
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Ear pain
subjects affected / exposed	3 / 897 (0.33%)	6 / 1657 (0.36%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	3	6	0	2
Excessive cerumen production
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	3	0	0
External ear inflammation
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Motion sickness
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Tympanosclerosis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Eye disorders
Astigmatism
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Eye pain
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Blepharitis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Glaucoma
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Keratitis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Swelling of eyelid
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Vision blurred
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Eye irritation
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Conjunctivitis allergic
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Blindness transient
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Eye swelling
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Chalazion
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Eye inflammation
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Eye pruritus
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Eyelid exfoliation
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Eyelid ptosis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Myopia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	3	0	2
Abdominal distension
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	2	0	1
Abdominal pain
subjects affected / exposed	7 / 897 (0.78%)	13 / 1657 (0.78%)	1 / 178 (0.56%)	11 / 906 (1.21%)
occurrences all number	7	17	1	12
Abdominal pain lower
subjects affected / exposed	3 / 897 (0.33%)	2 / 1657 (0.12%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	3	2	1	0
Abdominal pain upper
subjects affected / exposed	7 / 897 (0.78%)	18 / 1657 (1.09%)	2 / 178 (1.12%)	9 / 906 (0.99%)
occurrences all number	7	20	2	10
Anal fissure
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Colitis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	0	0	2
Constipation
subjects affected / exposed	3 / 897 (0.33%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	3	5	0	1
Dental caries
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	4	0	0
Diarrhoea
subjects affected / exposed	14 / 897 (1.56%)	13 / 1657 (0.78%)	5 / 178 (2.81%)	16 / 906 (1.77%)
occurrences all number	15	13	5	19
Dyspepsia
subjects affected / exposed	0 / 897 (0.00%)	5 / 1657 (0.30%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	5	1	0
Enteritis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Food poisoning
subjects affected / exposed	0 / 897 (0.00%)	5 / 1657 (0.30%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	0	5	1	2
Gastritis
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	2	0	2
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 897 (0.22%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	2	5	0	4
Haematemesis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Haemorrhoids
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	0	0	1	2
Hyperchlorhydria
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Hypoaesthesia oral
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Irritable bowel syndrome
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	1	0	2
Lip swelling
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Mouth ulceration
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	1	0	1	0
Nausea
subjects affected / exposed	245 / 897 (27.31%)	398 / 1657 (24.02%)	45 / 178 (25.28%)	204 / 906 (22.52%)
occurrences all number	324	500	59	262
Oral pain
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Pancreatitis relapsing
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Peptic ulcer
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Toothache
subjects affected / exposed	1 / 897 (0.11%)	7 / 1657 (0.42%)	1 / 178 (0.56%)	5 / 906 (0.55%)
occurrences all number	1	7	1	6
Vomiting
subjects affected / exposed	6 / 897 (0.67%)	12 / 1657 (0.72%)	1 / 178 (0.56%)	11 / 906 (1.21%)
occurrences all number	6	12	1	11
Oral pruritus
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Aphthous ulcer
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Coeliac disease
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Embedded tooth
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Eructation
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Flatulence
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Palatal disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Tongue discolouration
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Transient lingual papillitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Gingival pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Skin and subcutaneous tissue disorders
Pityriasis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Acne
subjects affected / exposed	8 / 897 (0.89%)	12 / 1657 (0.72%)	1 / 178 (0.56%)	7 / 906 (0.77%)
occurrences all number	8	14	1	7
Cold urticaria
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Dermatitis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	2	0	1
Dermatitis allergic
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Dermatitis atopic
subjects affected / exposed	1 / 897 (0.11%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	4	0	1
Dermatitis contact
subjects affected / exposed	3 / 897 (0.33%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	3	5	0	2
Eczema
subjects affected / exposed	4 / 897 (0.45%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	4	6	0	2
Erythema
subjects affected / exposed	3 / 897 (0.33%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	4	0	0	0
Hand dermatitis
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Hyperhidrosis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	2	0	2
Ingrowing nail
subjects affected / exposed	3 / 897 (0.33%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	3	1	0	1
Miliaria
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Pain of skin
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Pruritus
subjects affected / exposed	3 / 897 (0.33%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	3	1	0	0
Rash
subjects affected / exposed	3 / 897 (0.33%)	13 / 1657 (0.78%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	3	13	0	2
Rash macular
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Rash maculo-papular
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Rash pruritic
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	0	0	0
Skin lesion
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Urticaria
subjects affected / exposed	2 / 897 (0.22%)	4 / 1657 (0.24%)	1 / 178 (0.56%)	3 / 906 (0.33%)
occurrences all number	2	4	1	3
Alopecia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Drug eruption
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Nail disorder
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Psoriasis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Rash erythematous
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Seborrhoeic dermatitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Skin induration
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Urticaria chronic
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	5	0	1
Haematuria
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Hydronephrosis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Nephritis
subjects affected / exposed	3 / 897 (0.33%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	3	0	0	0
Nephrolithiasis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	2	0	1
Pollakiuria
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Urinary retention
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Urinary tract inflammation
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Thyroid stimulating hormone deficiency
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Growth hormone deficiency
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hyperthyroidism
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Thyroid cyst
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Musculoskeletal and connective tissue disorders
Joint swelling
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Muscular weakness
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	0	0	0	3
Intervertebral disc protrusion
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	3	0	1
Growing pains
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Foot deformity
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Flank pain
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Epiphysiolysis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Back pain
subjects affected / exposed	7 / 897 (0.78%)	15 / 1657 (0.91%)	2 / 178 (1.12%)	15 / 906 (1.66%)
occurrences all number	7	15	2	15
Axillary mass
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Arthritis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Arthralgia
subjects affected / exposed	154 / 897 (17.17%)	236 / 1657 (14.24%)	25 / 178 (14.04%)	127 / 906 (14.02%)
occurrences all number	205	290	30	163
Joint warmth
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Knee deformity
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Muscle swelling
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Muscle tightness
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Joint hyperextension
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Tenosynovitis
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Tendon pain
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Temporomandibular joint syndrome
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Spinal pain
subjects affected / exposed	2 / 897 (0.22%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	0	0	0
Sever's disease
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Rotator cuff syndrome
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Pain in extremity
subjects affected / exposed	5 / 897 (0.56%)	9 / 1657 (0.54%)	1 / 178 (0.56%)	11 / 906 (1.21%)
occurrences all number	5	12	1	11
Osteochondrosis
subjects affected / exposed	4 / 897 (0.45%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	4	0	0	1
Neck pain
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	1	3	0	3
Neck mass
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Myositis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Myalgia
subjects affected / exposed	240 / 897 (26.76%)	384 / 1657 (23.17%)	30 / 178 (16.85%)	209 / 906 (23.07%)
occurrences all number	325	500	35	276
Musculoskeletal chest pain
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	0	0	2
Rhabdomyolysis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Bone pain
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Coccydynia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Costochondritis
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	3	0	0
Joint effusion
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Myokymia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Pain in jaw
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Sacral pain
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Scoliosis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Short stature
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Spinal flattening
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Synovial cyst
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Tendonitis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Torticollis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Bacterial vaginosis
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	3	0	2
Acarodermatitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Acute sinusitis
subjects affected / exposed	0 / 897 (0.00%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	0	4	0	4
Adenovirus infection
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Asymptomatic COVID-19
subjects affected / exposed	3 / 897 (0.33%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	3	3	0	0
Enterovirus infection
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Enterobiasis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	1	0	2
Eye infection
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	0	0	1
Eyelid infection
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Folliculitis
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Gastroenteritis
subjects affected / exposed	6 / 897 (0.67%)	16 / 1657 (0.97%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	6	16	0	5
Body tinea
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	2	0	1
Bronchitis
subjects affected / exposed	2 / 897 (0.22%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	2	4	0	2
Bullous impetigo
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
COVID-19
subjects affected / exposed	93 / 897 (10.37%)	195 / 1657 (11.77%)	26 / 178 (14.61%)	107 / 906 (11.81%)
occurrences all number	96	198	26	111
COVID-19 pneumonia
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Cellulitis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	2	0	2
Chlamydial infection
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Coronavirus infection
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Cystitis
subjects affected / exposed	1 / 897 (0.11%)	5 / 1657 (0.30%)	1 / 178 (0.56%)	3 / 906 (0.33%)
occurrences all number	1	5	1	3
Ear infection
subjects affected / exposed	3 / 897 (0.33%)	2 / 1657 (0.12%)	1 / 178 (0.56%)	2 / 906 (0.22%)
occurrences all number	3	2	1	2
Endometritis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Erythema migrans
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Gastroenteritis viral
subjects affected / exposed	3 / 897 (0.33%)	7 / 1657 (0.42%)	0 / 178 (0.00%)	6 / 906 (0.66%)
occurrences all number	3	7	0	6
Genital herpes
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Gingivitis
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	1	0	0
Infected bite
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	1 / 906 (0.11%)
occurrences all number	0	0	1	1
Herpes zoster
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	1	3	1	0
Hordeolum
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	2	0	1
Impetigo
subjects affected / exposed	2 / 897 (0.22%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	2	0	0
Helicobacter gastritis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Infectious mononucleosis
subjects affected / exposed	2 / 897 (0.22%)	3 / 1657 (0.18%)	2 / 178 (1.12%)	0 / 906 (0.00%)
occurrences all number	2	3	2	0
Pharyngitis streptococcal
subjects affected / exposed	2 / 897 (0.22%)	6 / 1657 (0.36%)	1 / 178 (0.56%)	4 / 906 (0.44%)
occurrences all number	2	6	1	4
Localised infection
subjects affected / exposed	1 / 897 (0.11%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	1	4	0	4
Lower respiratory tract infection
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Lyme disease
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Mycoplasma genitalium infection
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Nasopharyngitis
subjects affected / exposed	29 / 897 (3.23%)	60 / 1657 (3.62%)	11 / 178 (6.18%)	37 / 906 (4.08%)
occurrences all number	33	65	11	42
Onychomycosis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Oral herpes
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	5 / 906 (0.55%)
occurrences all number	0	1	0	6
Otitis externa
subjects affected / exposed	4 / 897 (0.45%)	10 / 1657 (0.60%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	5	10	0	4
Otitis media
subjects affected / exposed	6 / 897 (0.67%)	6 / 1657 (0.36%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	6	6	0	3
Otitis media acute
subjects affected / exposed	3 / 897 (0.33%)	3 / 1657 (0.18%)	1 / 178 (0.56%)	1 / 906 (0.11%)
occurrences all number	4	3	1	2
Otosalpingitis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Paronychia
subjects affected / exposed	2 / 897 (0.22%)	5 / 1657 (0.30%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	2	5	0	1
Parotitis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Pelvic inflammatory disease
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Pharyngitis
subjects affected / exposed	8 / 897 (0.89%)	28 / 1657 (1.69%)	2 / 178 (1.12%)	19 / 906 (2.10%)
occurrences all number	9	30	2	24
Influenza
subjects affected / exposed	10 / 897 (1.11%)	22 / 1657 (1.33%)	1 / 178 (0.56%)	11 / 906 (1.21%)
occurrences all number	10	22	1	12
Postoperative wound infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Pulpitis dental
subjects affected / exposed	2 / 897 (0.22%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	2	1	0	2
Respiratory tract infection
subjects affected / exposed	1 / 897 (0.11%)	4 / 1657 (0.24%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	4	0	0
Respiratory tract infection bacterial
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Respiratory tract infection viral
subjects affected / exposed	2 / 897 (0.22%)	11 / 1657 (0.66%)	2 / 178 (1.12%)	7 / 906 (0.77%)
occurrences all number	3	14	2	8
Rhinitis
subjects affected / exposed	4 / 897 (0.45%)	6 / 1657 (0.36%)	2 / 178 (1.12%)	8 / 906 (0.88%)
occurrences all number	4	6	2	8
Rhinovirus infection
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Sialoadenitis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Sinusitis
subjects affected / exposed	4 / 897 (0.45%)	3 / 1657 (0.18%)	2 / 178 (1.12%)	3 / 906 (0.33%)
occurrences all number	4	3	2	3
Skin infection
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Soft tissue infection
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Streptococcal infection
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Suspected COVID-19
subjects affected / exposed	5 / 897 (0.56%)	10 / 1657 (0.60%)	0 / 178 (0.00%)	6 / 906 (0.66%)
occurrences all number	5	11	0	6
Tinea versicolour
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	2	0	0
Tonsillitis
subjects affected / exposed	10 / 897 (1.11%)	20 / 1657 (1.21%)	5 / 178 (2.81%)	15 / 906 (1.66%)
occurrences all number	10	22	6	17
Tonsillitis streptococcal
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	0	1	0	2
Tooth abscess
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	1	2	0	3
Tooth infection
subjects affected / exposed	1 / 897 (0.11%)	2 / 1657 (0.12%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	1	2	1	0
Yersinia infection
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	1	0	0
Tracheitis
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Trichomoniasis
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	35 / 897 (3.90%)	71 / 1657 (4.28%)	6 / 178 (3.37%)	42 / 906 (4.64%)
occurrences all number	38	74	6	46
Upper respiratory tract infection bacterial
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Urinary tract infection
subjects affected / exposed	9 / 897 (1.00%)	13 / 1657 (0.78%)	3 / 178 (1.69%)	9 / 906 (0.99%)
occurrences all number	11	17	3	10
Vaginal infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	1 / 906 (0.11%)
occurrences all number	0	1	2	1
Varicella
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Viral infection
subjects affected / exposed	5 / 897 (0.56%)	7 / 1657 (0.42%)	0 / 178 (0.00%)	5 / 906 (0.55%)
occurrences all number	5	8	0	6
Viral pharyngitis
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	3	0	0
Viral upper respiratory tract infection
subjects affected / exposed	3 / 897 (0.33%)	9 / 1657 (0.54%)	0 / 178 (0.00%)	4 / 906 (0.44%)
occurrences all number	3	9	0	4
Vulvovaginal candidiasis
subjects affected / exposed	2 / 897 (0.22%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	2	0	0	2
Vulvovaginal mycotic infection
subjects affected / exposed	1 / 897 (0.11%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	1	3	0	3
Wound infection
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	0	1	0
Laryngitis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Conjunctivitis
subjects affected / exposed	0 / 897 (0.00%)	9 / 1657 (0.54%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	9	0	0
Conjunctivitis viral
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Ear lobe infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Fungal foot infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Fungal skin infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Gastrointestinal viral infection
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Helminthic infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Herpes simplex
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Pericoronitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Parasitic gastroenteritis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Post-acute COVID-19 syndrome
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Skin bacterial infection
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	3	0	0
Subcutaneous abscess
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Tinea pedis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Vaccination site cellulitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Vaccination site pustule
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Vulvovaginitis
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	2	0	0
Laryngotracheitis obstructive
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Molluscum contagiosum
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Oral candidiasis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Pharyngotonsillitis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Metabolism and nutrition disorders
Insulin resistance
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	0	0	0	3
Iron deficiency
subjects affected / exposed	1 / 897 (0.11%)	6 / 1657 (0.36%)	0 / 178 (0.00%)	3 / 906 (0.33%)
occurrences all number	1	6	0	3
Lactose intolerance
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	1	0	0	0
Obesity
subjects affected / exposed	2 / 897 (0.22%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	2	2	0	1
Type 2 diabetes mellitus
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Vitamin B complex deficiency
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Vitamin B12 deficiency
subjects affected / exposed	0 / 897 (0.00%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	2	0	1
Abnormal loss of weight
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Folate deficiency
subjects affected / exposed	2 / 897 (0.22%)	2 / 1657 (0.12%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	2	0	0
Glucose tolerance impaired
subjects affected / exposed	2 / 897 (0.22%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	2	0	0	0
Gluten sensitivity
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	1 / 178 (0.56%)	0 / 906 (0.00%)
occurrences all number	0	1	1	0
Hypercholesterolaemia
subjects affected / exposed	1 / 897 (0.11%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	1	1	0	1
Hyperlipidaemia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	1	0	1
Hyponatraemia
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Zinc deficiency
subjects affected / exposed	0 / 897 (0.00%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	1 / 906 (0.11%)
occurrences all number	0	0	0	1
Vitamin D deficiency
subjects affected / exposed	1 / 897 (0.11%)	0 / 1657 (0.00%)	0 / 178 (0.00%)	2 / 906 (0.22%)
occurrences all number	1	0	0	2
Decreased appetite
subjects affected / exposed	0 / 897 (0.00%)	3 / 1657 (0.18%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	3	0	0
Haemochromatosis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hypoglycaemia
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0
Hypovitaminosis
subjects affected / exposed	0 / 897 (0.00%)	1 / 1657 (0.06%)	0 / 178 (0.00%)	0 / 906 (0.00%)
occurrences all number	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

23 May 2019

As per the recommendation from CBER, the scope of the study has been extended to include the 3-dose (0,2,6-M) schedule and an additional 2-dose schedule (0,6-M) along with the 2-dose (0,2-M) schedule planned originally. The study will assess the immunogenicity of the 2-dose and 3-doses vaccination with rMenB+OMV NZ vaccine along with effectiveness and safety.

18 Mar 2020

The scope of this post-marketing commitment study has been extended to demonstrate the effectiveness, immunogenicity and safety of GSK’s investigational combined meningococcal ABCWY vaccine (from a phase III MenABCWY study) along with the rMenB+OMV NZ vaccine.

23 Sep 2020

This protocol is amended primarily as a consequence of feedback from regulatory authorities of participating countries following their review of Protocol Amendment 2. Additional changes have been made to improve the clarity of the text.

09 May 2021

The protocol is being amended to document the increase in blood volumes drawn at certain visits (Visit 2 and Visit 6). The allowed windows for study visits during special circumstances have also been widened to maintain subject visit compliance during the COVID-19 pandemic. Additionally, considering that some of the study interventions are combination products constituted of a device and biologic product (pre-filled syringes), the amended protocol provides instructions for collection of safety information related to the use of medical devices. The reporting period for pregnancies has also been updated in line with the current guidelines

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A phase III, randomized, controlled, observer-blind study to demonstrate effectiveness, immunogenicity and safety of GSK's meningococcal Group B and combined ABCWY vaccines when administered to healthy adolescents and young adults.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 3-dose (0,2,6-M), 2-dose(0,6-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 3-dose (0,2,6-M), 2-dose(0,6-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 2-dose (0,2-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic US N. meningitidis serogroup B strains at 1 month after the 2-dose (0,2-M) vaccination schedule of rMenB+OMV and 1 dose of MenACWY

Primary: Geometric mean titers (GMTs) against serogroups A, C, W and Y for each lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 month after the last vaccination of MenABCWY

Primary: Geometric mean titers (GMTs) against serogroups A, C, W and Y for each lot (ABCWY-1 Group, ABCWY-2 Group and ABCWY-3 Group) at 1 month after the last vaccination of MenABCWY

Primary: Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the 2-dose (0,2-M) schedule of rMenB+OMV

Primary: Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the 2-dose (0,2-M) schedule of rMenB+OMV

Primary: Percentage of participants whose sera kill Greater Than or Equal to (>=) 70% of the strains tested using enc-hSBA at 1 month after the 3-dose (0,2,6-M) schedule of rMenB+OMV and 2-dose(0,6-M) schedule of rMenB+OMV

Primary: Percentage of participants whose sera kill Greater Than or Equal to (>=) 70% of the strains tested using enc-hSBA at 1 month after the 3-dose (0,2,6-M) schedule of rMenB+OMV and 2-dose(0,6-M) schedule of rMenB+OMV

Primary: Percentage of participants with 4-fold rise in hSBA titers against N. meningitidis serogroups A, C, W and Y at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group), relative to baseline

Primary: Percentage of participants with 4-fold rise in hSBA titers against N. meningitidis serogroups A, C, W and Y at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group), relative to baseline

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group)

Primary: Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after last MenABCWY vaccination (pooled lots) and MenACWY vaccination (for the ACWY Group)

Primary: Percentage of blood samples with bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (pooled lots) and 2-dose(0,2-M) schedule of rMenB+OMV

Primary: Percentage of blood samples with bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose (pooled lots) and 2-dose(0,2-M) schedule of rMenB+OMV

Primary: Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the last vaccination in the ABCWY Group (pooled lots)

Primary: Percentage of participants whose sera kill >=70% of the strains tested using enc-hSBA at 1 month after the last vaccination in the ABCWY Group (pooled lots)

Primary: Number of participants with any solicited local adverse events (AEs) after the first study intervention administration

Primary: Number of participants with any solicited local adverse events (AEs) after the first study intervention administration

Primary: Number of participants with any solicited local adverse events (AEs) after the second study intervention administration

Primary: Number of participants with any solicited local adverse events (AEs) after the second study intervention administration

Primary: Number of participants with any solicited local adverse events (AEs) after the third study intervention administration

Primary: Number of participants with any solicited local adverse events (AEs) after the third study intervention administration

Primary: Number of participants with any solicited systemic AEs after the first study intervention administration

Primary: Number of participants with any solicited systemic AEs after the first study intervention administration

Primary: Number of participants with any solicited systemic AEs after the second study intervention administration

Primary: Number of participants with any solicited systemic AEs after the second study intervention administration

Primary: Number of participants with any solicited systemic AEs after the third study intervention administration

Primary: Number of participants with any solicited systemic AEs after the third study intervention administration

Primary: Number of participants with any unsolicited AEs after the first study intervention administration

Primary: Number of participants with any unsolicited AEs after the first study intervention administration

Primary: Number of participants with any unsolicited AEs after the second study intervention administration

Primary: Number of participants with any unsolicited AEs after the second study intervention administration

Primary: Number of participants with any unsolicited AEs after the third study intervention administration

Primary: Number of participants with any unsolicited AEs after the third study intervention administration

Primary: Number of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs

Primary: Number of participants with SAEs, AEs leading to withdrawal, AESIs and medically attended AEs

Secondary: Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose and 3-dose (0,2,6-M), 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

Secondary: Percentage of blood samples without bactericidal serum activity against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the last MenABCWY dose and 3-dose (0,2,6-M), 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

Secondary: Percentage of participants with 4-fold rise in hSBA titers against N.meningitidis group B strains at 1 month after last MenABCWY dose (ABCWY group-pooled lots) and 1 month afte 2-dose(0,2-M) schedule of rMenB+OMV NZ relative to baseline

Secondary: Percentage of participants with 4-fold rise in hSBA titers against N.meningitidis group B strains at 1 month after last MenABCWY dose (ABCWY group-pooled lots) and 1 month afte 2-dose(0,2-M) schedule of rMenB+OMV NZ relative to baseline

Secondary: Percentage of blood samples without bactericidal serum activity using enc-hSBA against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

Secondary: Percentage of blood samples without bactericidal serum activity using enc-hSBA against each of the endemic U.S N. meningitidis serogroup B strains at 1 month after the 2-dose(0,6-M) schedule of rMenB+OMV and 1 dose of MenACWY

Secondary: Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination schedule for the MenB_0_2_6 group [3 dose], MenB_0_6 group and last MenABCWY dose (pooled lots)

Secondary: Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination schedule for the MenB_0_2_6 group [3 dose], MenB_0_6 group and last MenABCWY dose (pooled lots)

Secondary: Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: Percentage of participants classified by percentage of serogroup B invasive disease strains killed using enc-hSBA in each subject at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: Percentage of participants with hSBA titers >= LLOQ for each and all serogroup B indicator strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months and 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2 months)

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2 months)

Secondary: hSBA Geometric Mean Titres (GMTs) against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: hSBA Geometric Mean Titres (GMTs) against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: hSBA GMTs against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: hSBA GMTs against each of the N. meningitidis serogroup B strains at Day 1 and at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: hSBA Geometric Mean Ratios (GMRs) for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: hSBA Geometric Mean Ratios (GMRs) for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2,6-months, 0,6-months) and last dose of MenABCWY (ABCWY group-pooled lots)

Secondary: hSBA GMRs for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: hSBA GMRs for each of the N. meningitidis serogroup B strains at 1 month after vaccination with rMenB+OMV NZ (0,2-months)

Secondary: Percentage of participants with hSBA titers >= LLOQ for each of the N. meningitidis serogroups A,C,W,Y at Day 1 and at 1 month after the first and the last MenABCWY vaccination for ABCWY_Pooled group and 1 month after the MenACWY vaccine for ACWY group

Secondary: Percentage of participants with hSBA titers >= LLOQ for each of the N. meningitidis serogroups A,C,W,Y at Day 1 and at 1 month after the first and the last MenABCWY vaccination for ABCWY_Pooled group and 1 month after the MenACWY vaccine for ACWY group

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first MenABCWY dose for ABCWY_Pooled group compared to the MenACWY vaccine for ACWY group relative to baseline (Day 1)

Secondary: Percentage of participants with 4-fold rise in hSBA titers for each of the N. meningitidis serogroups A, C, W and Y at 1 month after the first MenABCWY dose for ABCWY_Pooled group compared to the MenACWY vaccine for ACWY group relative to baseline (Day 1)

Secondary: hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and the last MenABCWY vaccination for the ABCWY_Pooled group and at 1 month after the MenACWY vaccination for ACWY Group

Secondary: hSBA GMTs against each of the N. meningitidis serogroups A, C, W and Y at Day 1 and 1 month after the first and the last MenABCWY vaccination for the ABCWY_Pooled group and at 1 month after the MenACWY vaccination for ACWY Group

Clinical Trial Results:
A phase III, randomized, controlled, observer-blind study to demonstrate effectiveness, immunogenicity and safety of GSK's meningococcal Group B and combined ABCWY vaccines when administered to healthy adolescents and young adults.