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Clinical Trial Results:
A Phase 2b Trial To Assess the Safety, Tolerability, And Immunogenicity of MenABCWY in Healthy Infants 2 and 6 Months of Age

Summary
EudraCT number	2020-000948-60
Trial protocol	DE GR
Global end of trial date	15 Sep 2022

Results information
Results version number	v1(current)
This version publication date	30 Mar 2023
First version publication date	30 Mar 2023
Other versions

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

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Trial information

Top of page

Sponsor protocol code

C3511002

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

Scientific contact

Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com

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

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

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

Yes

Analysis stage

Final

Date of interim/final analysis

10 Nov 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Sep 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

To describe the immune response for Neisseria meningitidis group A (MenA), MenC, MenW, and MenY induced by Neisseria meningitidis group A, B, C, W, and Y vaccine (MenABCWY) compared to the immune response induced by Nimenrix after 2 primary vaccinations and after a booster dose. To describe the immune response for MenB induced by MenABCWY compared to the immune response induced by Bexsero after 2 primary vaccinations and after a booster dose. To describe the immune response for MenB induced by 60 micrograms (mcg) and 120 mcg of bivalent rLP2086 after 2 primary vaccinations and after a booster dose. To describe the safety profile of MenABCWY after primary vaccinations, by protocol-assigned paracetamol regimen, and after a booster dose.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Nov 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Greece: 24

Country: Number of subjects enrolled

Spain: 298

Worldwide total number of subjects

325

EEA total number of subjects

325

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)

325

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

326 subjects signed the informed consent form. Out of which 1 subject was not vaccinated as parent withdrew consent. 325 subjects received vaccination.

Period 1 title

Vaccination phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group 1 (MenABCWY +PLP)

Arm description

Infant subjects aged 6 months were administered a single intramuscular injection of 0.5 millilitre (mL) MenABCWY into the left thigh. Prophylactic liquid paracetamol regimen (PLP) was administered orally with 3 required doses, the first dose starting 30 minutes before vaccination (Day 1 [primary vaccination {vacc}1] and Month 2 [primary vaccination 2]). Subjects received a single intramuscular injection of MenABCWY approximately 6 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at Day 1.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

5-mL dose administered orally

Group 2 (MenABCWY)

Arm description

Infant subjects aged 6 months were administered a single intramuscular injection of 0.5 mL MenABCWY into the left thigh at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). Subjects received a single intramuscular injection of MenABCWY approximately 6 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at Day 1.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.25 mL bivalent rLP2086 (60 microgram [μg]) into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). PLP or SLP was administered orally. Subjects received a single intramuscular injection of 0.25 mL bivalent rLP2086 (60 μg) into the left thigh and 0.5 mL of Nimenrix into the right thigh approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Arm type

Experimental

Investigational medicinal product name

rLP2086

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25-mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 4 (60 μg rLP2086 +Nimenrix)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.25 mL of bivalent rLP2086 (60 μg) into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). Subjects received a single intramuscular injection of 0.25 mL of bivalent rLP2086 (60 μg) into the left thigh and 0.5 mL of Nimenrix into the right thigh approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Arm type

Experimental

Investigational medicinal product name

rLP2086

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly.

Group 5 (120 μg rLP2086 +Nimenrix +PLP)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL of bivalent rLP2086 (120 μg) into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). PLP was administered orally with 3 required doses, the first dose starting 30 minutes before vaccination at Day 1 and Month 2. Subjects received a single intramuscular injection of 0.5 mL of bivalent rLP2086 (120 μg) into the left thigh and 0.5 mL of Nimenrix into the right thigh approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Arm type

Experimental

Investigational medicinal product name

rLP2086

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Group 7 (MenABCWY +SLP)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL MenABCWY into the left thigh. Scheduled liquid paracetamol (SLP) was administered orally at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). Subjects received a single intramuscular injection of 0.5 mL MenABCWY approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 8 (Bexsero +Nimenrix +PLP)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL of Bexsero into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). PLP was administered orally with 3 required doses, the first dose starting 30 minutes before vaccination at Day 1 and Month 2. Subjects received a single intramuscular injection of 0.5 mL of Bexsero into the left thigh and 0.5 mL of Nimenrix into the right thigh approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Arm type

Active comparator

Investigational medicinal product name

Bexsero

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered inteamuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 10 (Bexsero +Nimenrix)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL of Bexsero into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1), Month 2 (primary vaccination 2) and at approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Arm type

Active comparator

Investigational medicinal product name

Bexsero

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Group 11 (MenABCWY +TLP)

Arm description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL MenABCWY into the left thigh at Day 1 (primary vaccination 1). Therapeutic Liquid Paracetamol regimen (TLP) was administered orally. No subjects received Vaccination 2 and booster dose due to study termination. All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 months of age.

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Number of subjects in period 1	Group 1 (MenABCWY +PLP)	Group 2 (MenABCWY)	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)	Group 7 (MenABCWY +SLP)	Group 8 (Bexsero +Nimenrix +PLP)	Group 10 (Bexsero +Nimenrix)	Group 11 (MenABCWY +TLP)
Started	23	25	36	16	53	50	55	55	12
Completed	22	25	20	0	2	0	25	22	0
Not completed	1	0	16	16	51	50	30	33	12
Adverse event, serious fatal	-	-	-	-	-	1	-	-	-
Adverse event, non-fatal	1	-	-	-	-	-	1	-	-
No longer meets eligibility criteria	-	-	-	-	-	-	-	1	-
Study terminated by sponsor	-	-	14	15	47	43	29	29	12
Unspecified	-	-	-	-	-	2	-	-	-
Lost to follow-up	-	-	-	-	-	-	-	1	-
Withdrawal by parent/guardian	-	-	2	1	3	4	-	2	-
Protocol deviation	-	-	-	-	1	-	-	-	-

Period 2 title

Primary Follow-up Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Group 1 (MenABCWY +PLP)

Arm description

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 2 (MenABCWY)

Arm description

Arm type

Experimental

Investigational medicinal product name

MenABCWY

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)

Arm description

Arm type

Experimental

Investigational medicinal product name

rLP2086

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25-mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 5 (120 μg rLP2086 +Nimenrix +PLP)

Arm description

Arm type

Experimental

Investigational medicinal product name

rLP2086

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 8 (Bexsero +Nimenrix +PLP)

Arm description

Arm type

Active comparator

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Bexsero

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Paracetamol

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral suspension

Routes of administration

Oral use

Dosage and administration details

2.5-mL dose administered orally

Group 10 (Bexsero +Nimenrix)

Arm description

Infant subjects aged 2 months were administered single intramuscular injection of Bexsero and Nimenrix into the left thigh at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). Subjects received a single intramuscular injection of Bexsero and Nimenrix approximately 6 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months for age.

Arm type

Active comparator

Investigational medicinal product name

Bexsero

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose administered intramuscularly

Investigational medicinal product name

Vaxelis

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Investigational medicinal product name

Nimenrix

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5-mL dose administered intramuscularly

Number of subjects in period 2	Group 1 (MenABCWY +PLP)	Group 2 (MenABCWY)	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)	Group 8 (Bexsero +Nimenrix +PLP)	Group 10 (Bexsero +Nimenrix)
Started	22	25	20	2	25	22
Completed	22	25	20	2	25	21
Not completed	0	0	0	0	0	1
Lost to follow-up	-	-	-	-	-	1

Baseline characteristics

Top of page

Reporting group title

Group 1 (MenABCWY +PLP)

Reporting group description

Reporting group title

Group 2 (MenABCWY)

Reporting group description

Reporting group title

Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)

Reporting group description

Reporting group title

Group 4 (60 μg rLP2086 +Nimenrix)

Reporting group description

Reporting group title

Group 5 (120 μg rLP2086 +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 7 (MenABCWY +SLP)

Reporting group description

Reporting group title

Group 8 (Bexsero +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 10 (Bexsero +Nimenrix)

Reporting group description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL of Bexsero into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1), Month 2 (primary vaccination 2) and at approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Reporting group title

Group 11 (MenABCWY +TLP)

Reporting group description

Reporting group values	Group 1 (MenABCWY +PLP)	Group 2 (MenABCWY)	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)	Group 7 (MenABCWY +SLP)	Group 8 (Bexsero +Nimenrix +PLP)	Group 10 (Bexsero +Nimenrix)	Group 11 (MenABCWY +TLP)	Total
Number of subjects	23	25	36	16	53	50	55	55	12	325
Age Categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	23	25	36	16	53	50	55	55	12	325
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0	0
Age Continuous
Units: days
arithmetic mean (standard deviation)	158.5 ( 6.87 )	161.6 ( 14.45 )	71.1 ( 7.00 )	67.6 ( 5.81 )	68.9 ( 6.39 )	68.0 ( 5.99 )	67.4 ( 7.89 )	67.5 ( 7.30 )	69.4 ( 7.69 )	-
Gender Categorical
Units: Subjects
Female	12	10	21	7	24	27	32	20	7	160
Male	11	15	15	9	29	23	23	35	5	165
Race
Units: Subjects
White	20	24	35	16	52	50	55	55	12	319
Black or African American	1	1	1	0	0	0	0	0	0	3
Asian	0	0	0	0	0	0	0	0	0	0
Unknown	0	0	0	0	0	0	0	0	0	0
Multiracial	0	0	0	0	0	0	0	0	0	0
Not reported	2	0	0	0	1	0	0	0	0	3
Ethnicity
Units: Subjects
Hispanic or Latino	13	9	21	8	10	25	18	22	6	132
Non-Hispanic/non-Latino	10	16	15	8	43	25	37	33	6	193

End points

Top of page

Reporting group title

Group 1 (MenABCWY +PLP)

Reporting group description

Reporting group title

Group 2 (MenABCWY)

Reporting group description

Reporting group title

Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)

Reporting group description

Reporting group title

Group 4 (60 μg rLP2086 +Nimenrix)

Reporting group description

Reporting group title

Group 5 (120 μg rLP2086 +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 7 (MenABCWY +SLP)

Reporting group description

Reporting group title

Group 8 (Bexsero +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 10 (Bexsero +Nimenrix)

Reporting group description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL of Bexsero into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1), Month 2 (primary vaccination 2) and at approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Reporting group title

Group 11 (MenABCWY +TLP)

Reporting group description

Reporting group title

Group 1 (MenABCWY +PLP)

Reporting group description

Reporting group title

Group 2 (MenABCWY)

Reporting group description

Reporting group title

Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)

Reporting group description

Reporting group title

Group 5 (120 μg rLP2086 +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 8 (Bexsero +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 10 (Bexsero +Nimenrix)

Reporting group description

Subject analysis set title

Group 7 and 11 Combined

Subject analysis set type

Sub-group analysis

Subject analysis set description

Group7: Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL MenABCWY into the left thigh. Scheduled liquid paracetamol (SLP) was administered orally at Day 1 (primary vaccination 1) and Month 2 (primary vaccination 2). Subjects received a single intramuscular injection of 0.5 mL MenABCWY approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age. Group11: Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL MenABCWY into the left thigh at Day 1 (primary vaccination 1). Therapeutic Liquid Paracetamol regimen (TLP) was administered orally. No subjects received Vaccination 2 and booster dose due to study termination. All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 months of age.

Subject analysis set title

Group 8 and 10 Combined

Subject analysis set type

Sub-group analysis

Subject analysis set description

Group8:Infant subjects aged 2 months were administered single IM injection of 0.5mL of Bexsero into left thigh, 0.5mL of Nimenrix into right thigh at Day 1(primary vaccination 1) and Month 2(primary vaccination 2).PLP was administered orally with 3 required doses,first dose starting 30 minutes before vaccination at Day1 and Month2.Subjects received single IM injection of 0.5mL of Bexsero into left thigh and 0.5mL of Nimenrix into right thigh approximately 10 months after vaccination 1 (booster vaccination).Subjects received single IM injection of Prevenar 13 and Vaxelis into right thigh at 2,4 months of age.Group10:Infant subjects aged 2 months were administered single IM injection of 0.5mL of Bexsero into left thigh,0.5mL of Nimenrix into right thigh at Day 1(primary vaccination 1), Month 2(primary vaccination 2) and approximately 10 months after vaccination1 (booster vaccination).Subjects received single IM injection of Prevenar 13 and Vaxelis into right thigh at 2,4 months of age.

Subject analysis set title

Group 3 and 4 Combined

Subject analysis set type

Sub-group analysis

Subject analysis set description

Group3:Infant subjects aged 2 months were administered single IM injection of 0.25mL bivalent rLP2086(60μg) into left thigh,0.5mL Nimenrix into right thigh at Day 1(primary vacc 1),Month 2(primary vacc 2).PLP or SLP administered orally.Subjects received single IM injection of 0.25mL bivalent rLP2086(60 μg) into left thigh and 0.5mL Nimenrix into right thigh approx. 10 months after vacc1(booster vacc).Subjects received single IM injection of Prevenar 13,Vaxelis into right thigh at 2 and 4 months of age.Group4: Infant subjects aged 2 months were administered single IM injection of 0.25 mL bivalent rLP2086(60 μg) into left thigh,0.5 mL Nimenrix into right thigh at Day 1(primary vacc 1) and Month 2(primary vacc 2).Subjects received single IM injection of 0.25mL of bivalent rLP2086(60 μg) into left thigh and 0.5 mL of Nimenrix into right thigh approx.10 months after vacc 1(booster vacc).Subjects received single IM injection of Prevenar 13,Vaxelis into right thigh at 2 and 4 months of age.

Primary: Percentage of Subjects Achieving hSBA Titer >=LLOQ for Each MenA, MenC, MenW and MenY Test Strains 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects Achieving hSBA Titer >=LLOQ for Each MenA, MenC, MenW and MenY Test Strains 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[1] ^[2]

End point description

Percentage of subjects achieving serum human complement (hSBA) titer greater than or equal to (>=) lowe limit of quantitation (LLOQ) (1:8) for each MenA, MenC, MenW and MenY test strains were reported in this endpoint. Exact 2-sided confidence interval (CI) using the Clopper and Pearson method was presented. Post-primary vaccination 2 evaluable immunogenicity population: subjects randomized to study group of interest; eligible through Visit (V)4;received vaccine at V1 and V3;blood drawn for assay testing within required timeframes at V4; had at least 1 valid, determinate MenA, MenC, MenW, MenY, or MenB assay result at V4; received no prohibited vaccines/treatment and had no protocol deviations through V4. Here, ''Number of Subjects Analysed'' signifies subjects evaluable for this end point; and 'n'=subjects evaluable for specified rows. No serum samples were collected for subjects in Group 11 due to study termination.

End point type

Primary

End point timeframe

1 month after primary Vaccination 2

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was analyzed only for specified reporting arms.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 (MenABCWY +SLP)	Group 8 and 10 Combined
Number of subjects analysed	16	92
Units: Percentage of subjects
number (confidence interval 95%)
MenA (n=16,90)	100.0 (79.4 to 100.0)	100.0 (96.0 to 100.0)
MenC (n=16,91)	100.0 (79.4 to 100.0)	100.0 (96.0 to 100.0)
MenW (n=16,91)	100.0 (79.4 to 100.0)	100.0 (96.0 to 100.0)
MenY (n=16,92)	100.0 (79.4 to 100.0)	100.0 (96.1 to 100.0)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenACWY MenA, MenC, MenW and MenY Test Strains 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenACWY MenA, MenC, MenW and MenY Test Strains 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[3]

End point description

Percentage of subjects achieving hSBA titer >= LLOQ (1:8) for each MenA, MenC, MenW and MenY test strains were reported in this endpoint. Exact 2-sided CI using the Clopper and Pearson method was presented. Post–booster vaccination evaluable immunogenicity population: subjects randomized to study group of interest; eligible through V6;received vaccine at V1, V3 and 5;blood drawn for assay testing within required timeframes at V6; had at least 1 valid, determinate MenA, MenC, MenW, MenY, or MenB assay result at V6; received no prohibited vaccines/treatment and had no protocol deviations through V6. Here, ''Number of Subjects Analysed'' signifies subjects evaluable for this end point; and 'n'=subjects evaluable for specified rows. No serum samples were collected post-booster for subjects in Group 7 and Group 11 due to study termination.

End point type

Primary

End point timeframe

1 Month after booster vaccination

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: This endpoint was analyzed only for specified reporting arms.

End point values	Group 8 and 10 Combined
Number of subjects analysed	42
Units: Percentage of subjects
number (confidence interval 95%)
MenA (n=41,0)	100.0 (91.4 to 100.0)
MenC (n=41,0)	100.0 (91.4 to 100.0)
MenW (n=42,0)	100.0 (91.6 to 100.0)
MenY (n=41,0)	100.0 (91.4 to 100.0)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[4] ^[5]

End point description

Percentage of subjects achieving hSBA titer>= LLOQ for each MenB test strain(1:16 for strainA22 and1:8 for strain B44)reported.Exact 2-sided CI using Clopper and Pearson method.Post-primary vaccination 2 evaluable immunogenicity population=subjects randomised to study group of interest,eligible through Visit 4:fulfilling all inclusion criteria and none of exclusion criteria at each visit where eligibility criteria collected and confirmed,received investigational products at Visits1, 3 as randomised,blood drawn for assay testing within required time frames at Visit 4(1month after primary vaccination 2 [window 28-42 days]),at least 1 valid,determinate MenA,MenC,MenW,MenY, or MenB assay result at Visit 4,received no prohibited vaccines or treatment through Visit 4,no important protocol deviations through Visit 4.Here, ''Number of Subjects Analysed'' signifies subjects evaluable for this end point; and 'n'=subjects evaluable for specified rows.

End point type

Primary

End point timeframe

1 Month After primary Vaccination 2

Notes
[4] - 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: This endpoint was analyzed only for specified reporting arms.
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 (MenABCWY +SLP)	Group 8 and 10 Combined
Number of subjects analysed	18	95
Units: Percentage of subjects
number (confidence interval 95%)
PMB80 (A22) n=18, 94	44.4 (21.5 to 69.2)	9.6 (4.5 to 17.4)
PMB2707 (B44) n=18,95	88.9 (65.3 to 98.6)	29.5 (20.6 to 39.7)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 3 and 4 Combined Versus Group 5

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End point title

Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 3 and 4 Combined Versus Group 5 ^[6] ^[7]

End point description

Percentage of subjects achieving hSBA titer>= LLOQ for each MenB test strain(1:16 for strainA22 and1:8 for strain B44)reported.Exact 2-sided CI using Clopper and Pearson method.Post-primary vaccination 2 evaluable immunogenicity population=subjects randomised to study group of interest,eligible through Visit 4:fulfilling all inclusion criteria and none of exclusion criteria at each visit where eligibility criteria collected and confirmed,received investigational products at Visits1, 3 as randomised,blood drawn for assay testing within required time frames at Visit 4(1month after primary vaccination 2 [window 28-42 days]),at least 1 valid,determinate MenA,MenC,MenW,MenY, or MenB assay result at Visit 4,received no prohibited vaccines or treatment through Visit 4,no important protocol deviations through Visit 4. Here, ''Number of Subjects Analysed'' signifies subjects evaluable for this end point; and 'n'=subjects evaluable for specified rows.

End point type

Primary

End point timeframe

1 Month after primary vaccination 2

Notes
[6] - 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: This endpoint was analyzed only for specified reporting arms.
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analyzed only for specified reporting arms.

End point values	Group 5 (120 μg rLP2086 +Nimenrix +PLP)	Group 3 and 4 Combined
Number of subjects analysed	44	30
Units: Percentage of subjects
number (confidence interval 95%)
PMB80 (A22) n=44,30	47.7 (32.5 to 63.3)	46.7 (28.3 to 65.7)
PMB2707 (B44) n=45, 35	97.8 (88.2 to 99.9)	82.9 (66.4 to 93.4)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[8]

End point description

Percentage of subjects achieving hSBA titer>= LLOQ for each MenB test strain(1:16 for strain A22 and1:8 for strain B44)reported.Exact 2-sided CI using Clopper and Pearson method.Post–booster vaccination evaluable immunogenicity population=randomised to study group of interest,eligible through Visit 6, ie, fulfilling inclusion criteria,none of exclusion criteria at each visit where eligibility criteria were collected and confirmed.Received investigational products at Visits1,3,5 as randomised,blood drawn for assay testing within required time frames at Visit 6(1 month after booster vaccination[window 28-42 days]).At least 1 valid and determinate MenA,MenC, MenW,MenY,orMenB assay result at Visit 6, received no prohibited vaccines or treatment through Visit 6,no important protocol deviations through Visit 6.Number of subjects analysed=subjects evaluable for end point;n=subjects evaluable for specific rows.No serum sample collected for subjects in Group 7 and 11 due to study termination.

End point type

Primary

End point timeframe

1 Month after booster vaccination

Notes
[8] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 8 and 10 Combined
Number of subjects analysed	41
Units: Percentage of subjects
number (confidence interval 95%)
PMB80 (A22) n=40,0	25.0 (12.7 to 41.2)
PMB2707 (B44) n=41,0	34.1 (20.1 to 50.6)

No statistical analyses for this end point

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Groups 3, 4 and 5

Top of page

End point title

Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Groups 3, 4 and 5 ^[9] ^[10]

End point description

Percentage of subjects achieving hSBA titer >= LLOQ for each MenB test strain(1:16 for strain A22 and 1:8 for strain B44)reported.Exact 2-sided CI using Clopper and Pearson method.Post–booster vaccination evaluable immunogenicity population= randomised to study group of interest,eligible through Visit 6, ie, fulfilling inclusion criteria,none of exclusion criteria at each visit where eligibility criteria were collected and confirmed.Received investigational products at Visits 1, 3, 5 as randomised,blood drawn for assay testing within required time frames at Visit 6(1 month after booster vaccination[window 28-42 days]).At least 1 valid and determinate MenA,MenC, MenW,MenY,orMenB assay result at Visit 6, received no prohibited vaccines or treatment through Visit 6,no important protocol deviations through Visit 6.Number of subjects analysed=subjects evaluable for end point.

End point type

Primary

End point timeframe

1 Month after booster vaccination

Notes
[9] - 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: This endpoint was analyzed only for specified reporting arms.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analyzed only for specified reporting arms.

End point values	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Number of subjects analysed	18	0 ^[11]	0 ^[12]
Units: Percentage of subjects
number (confidence interval 95%)
PMB80 (A22)	38.9 (17.3 to 64.3)	( to )	( to )
PMB2707 (B44)	83.3 (58.6 to 96.4)	( to )	( to )

Notes
[11] - No serum samples were collected for subjects in this group due to study termination.
[12] - No serum samples were collected for subjects in this group due to study termination.

No statistical analyses for this end point

Primary: Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[13]

End point description

Local reactions included tenderness at injection site, redness and swelling and were recorded by subject’s parents/legal guardians in an electronic diary (e-diary). Redness and swelling were measured and recorded in caliper units. 1 caliper unit =0.5 centimeter (cm) and graded as mild: 0.5 to 2.0 cm, moderate: >2.0 to 7.0 cm and severe: >7.0 cm. Tenderness at injection site was graded as mild: hurt if gently touched, moderate: hurt if gently touched with crying and severe: caused limitation of limb movement. Exact 2-sided CI was based on the Clopper and Pearson method. Primary vaccination 1 safety population included all randomised subjects who received the first dose of investigational product at Visit 1 and had safety follow-up between Visit 1 and prior to Visit 3. Here, ‘Number of Subjects Analysed’ (N)=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 7 Days after primary Vaccination 1

Notes
[13] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	108
Units: Percentage of subjects
number (confidence interval 95%)
Redness: Mild	22.6 (12.9 to 35.0)	23.1 (15.6 to 32.2)
Redness: Moderate	11.3 (4.7 to 21.9)	6.5 (2.6 to 12.9)
Redness: Severe	0 (0.0 to 5.8)	0 (0.0 to 3.4)
Swelling: Mild	21.0 (11.7 to 33.2)	22.2 (14.8 to 31.2)
Swelling: Moderate	17.7 (9.2 to 29.5)	12.0 (6.6 to 19.7)
Swelling: Severe	0 (0.0 to 5.8)	0 (0.0 to 3.4)
Tenderness at injection site: Mild	22.6 (12.9 to 35.0)	25.9 (18.0 to 35.2)
Tenderness at injection site: Moderate	48.4 (35.5 to 61.4)	24.1 (16.4 to 33.3)
Tenderness at injection site: Severe	0 (0.0 to 5.8)	0.9 (0.0 to 5.1)

No statistical analyses for this end point

Primary: Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[14]

End point description

Local reactions included tenderness at injection site, redness and swelling and were recorded by subject’s parents/legal guardians in an electronic diary (e-diary). Redness and swelling were measured and recorded in caliper units. 1 caliper unit =0.5 centimeter (cm) and graded as mild: 0.5 to 2.0 cm, moderate: >2.0 to 7.0 cm and severe: >7.0 cm. Tenderness at injection site was graded as mild: hurt if gently touched, moderate: hurt if gently touched with crying and severe: caused limitation of limb movement. Exact 2-sided CI was based on the Clopper and Pearson method. Primary vaccination 2 safety population included all subjects who received the second dose of investigational product at Visit 3 and who had safety follow-up between Visit 3 and prior to Visit 4. Here, ‘Number of Subjects Analysed’ (N)=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 7 Days after primary Vaccination 2

Notes
[14] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	41	107
Units: Percentage of subjects
number (confidence interval 95%)
Redness: Mild	26.8 (14.2 to 42.9)	27.1 (19.0 to 36.6)
Redness: Moderate	12.2 (4.1 to 26.2)	11.2 (5.9 to 18.8)
Redness: Severe	0 (0.0 to 8.6)	0 (0.0 to 3.4)
Swelling: Mild	19.5 (8.8 to 34.9)	25.2 (17.3 to 34.6)
Swelling: Moderate	14.6 (5.6 to 29.2)	12.1 (6.6 to 19.9)
Swelling: Severe	0 (0.0 to 8.6)	0 (0.0 to 3.4)
Tenderness at injection site: Mild	22.0 (10.6 to 37.6)	27.1 (19.0 to 36.6)
Tenderness at injection site: Moderate	34.1 (20.1 to 50.6)	23.4 (15.7 to 32.5)
Tenderness at injection site: Severe	4.9 (0.6 to 16.5)	2.8 (0.6 to 8.0)

No statistical analyses for this end point

Primary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[15]

End point description

Systemic events were recorded by subject’s parents/legal guardians in e-diary. Fever was defined as temperature >=38.0 degrees (deg) Celsius(C) and was categorised as 38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Exact 2-sided CI was based on the Clopper and Pearson method. Decreased appetite was categorized as Mild:decreased interest in eating, Moderate:decreased oral intake,Severe: refusal to feed. Drowsiness: Mild: Increased or prolonged sleeping bouts,Moderate: Slightly subdued interfering with daily activity, Severe; Disabling, not interested in usual daily activity. Irritability; Mild: Easily consolable, Moderate: requiring increased attention,Severe: Inconsolable; crying could not be comforted. Primary vaccination 1 safety population included all randomised subjects who received the first dose of investigational product at Visit 1 and had safety follow-up between Visit 1 and prior to Visit 3. Here, ‘N’=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 7 Days after primary Vaccination 1

Notes
[15] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	108
Units: Percentage of subjects
number (confidence interval 95%)
Fever: ≥38.0°C	62.9 (49.7 to 74.8)	21.3 (14.0 to 30.2)
Fever: 38.0°C to 38.4°C	29.0 (18.2 to 41.9)	15.7 (9.4 to 24.0)
Fever: >38.4°C to 38.9°C	24.2 (14.2 to 36.7)	5.6 (2.1 to 11.7)
Fever: >38.9°C to 40.0°C	9.7 (3.6 to 19.9)	0 (0.0 to 3.4)
Fever: >40.0°C	0 (0.0 to 5.8)	0 (0.0 to 3.4)
Decreased appetite: Mild	17.7 (9.2 to 29.5)	17.6 (10.9 to 26.1)
Decreased appetite: Moderate	43.5 (31.0 to 56.7)	21.3 (14.0 to 30.2)
Decreased appetite: Severe	4.8 (1.0 to 13.5)	0.9 (0.0 to 5.1)
Irritability: Mild	21.0 (11.7 to 33.2)	19.4 (12.5 to 28.2)
Irritability: Moderate	59.7 (46.4 to 71.9)	45.4 (35.8 to 55.2)
Irritability: Severe	14.5 (6.9 to 25.8)	6.5 (2.6 to 12.9)
Drowsiness: Mild	37.1 (25.2 to 50.3)	39.8 (30.5 to 49.7)
Drowsiness: Moderate	32.3 (20.9 to 45.3)	18.5 (11.7 to 27.1)
Drowsiness: Severe	4.8 (1.0 to 13.5)	0.9 (0.000 to 5.1)
Use of antipyretic medication	46.8 (34.0 to 59.9)	50.0 (40.2 to 59.8)

No statistical analyses for this end point

Primary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Top of page

End point title

Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[16]

End point description

Systemic events were recorded by subject’s parents/legal guardians in e-diary. Fever was defined as temperature >=38.0 degrees (deg) Celsius(C) and was categorised as 38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Exact 2-sided CI was based on the Clopper and Pearson method. Decreased appetite was categorized as Mild:decreased interest in eating, Moderate:decreased oral intake,Severe: refusal to feed. Drowsiness: Mild: Increased or prolonged sleeping bouts,Moderate: Slightly subdued interfering with daily activity, Severe; Disabling, not interested in usual daily activity. Irritability; Mild: Easily consolable, Moderate: requiring increased attention,Severe: Inconsolable; crying could not be comforted. Primary vaccination 2 safety population included all subjects who received the second dose of investigational product at Visit 3 and who had safety follow-up between Visit 3 and prior to Visit 4. Here, ‘N’=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 7 Days after primary Vaccination 2

Notes
[16] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	41	107
Units: Percentage of subjects
number (confidence interval 95%)
Fever: ≥38.0°C	65.9 (49.4 to 79.9)	48.6 (38.8 to 58.5)
Fever: 38.0°C to 38.4°C	26.8 (14.2 to 42.9)	31.8 (23.1 to 41.5)
Fever: >38.4°C to 38.9°C	26.8 (14.2 to 42.9)	14.0 (8.1 to 22.1)
Fever: >38.9°C to 40.0°C	12.2 (4.1 to 26.2)	2.8 (0.6 to 8.0)
Fever: >40.0°C	0 (0.0 to 8.6)	0 (0.0 to 3.4)
Decreased appetite: Mild	22.0 (10.6 to 37.6)	20.6 (13.4 to 29.5)
Decreased appetite: Moderate	31.7 (18.1 to 48.1)	25.2 (17.3 to 34.6)
Decreased appetite: Severe	4.9 (0.6 to 16.5)	3.7 (1.0 to 9.3)
Irritability: Mild	12.2 (4.1 to 26.2)	21.5 (14.1 to 30.5)
Irritability: Moderate	53.7 (37.4 to 69.3)	48.6 (38.8 to 58.5)
Irritability: Severe	22.0 (10.6 to 37.6)	6.5 (2.7 to 13.0)
Drowsiness: Mild	29.3 (16.1 to 45.5)	45.8 (36.1 to 55.7)
Drowsiness: Moderate	34.1 (20.1 to 50.6)	14.0 (8.1 to 22.1)
Drowsiness: Severe	4.9 (0.6 to 16.5)	0.9 (0.0 to 5.1)
Use of antipyretic medication	41.5 (26.3 to 57.9)	72.9 (63.4 to 81.0)

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[17]

End point description

An Adverse Event (AE) was any untoward medical occurrence in a subject, temporally associated with the use of investigational product, whether or not considered related to the investigational product. Serious Adverse Events (SAE) was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalisation or prolongation of existing hospitalisation; was life-threatening; resulted in persistent disability/incapacity; congenital anomaly/birth defect and other important medical events. Medically Attended Adverse Events (MAE) was defined as a nonserious AE that resulted in an evaluation at a medical facility.Newly Diagnosed Chronic Medical Condition (NDCMC) was defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects. Safety population included all randomised subjects who received at least 1 dose of investigational product and had safety data reported after vaccination.

End point type

Primary

End point timeframe

Within 30 Days after primary Vaccination 1

Notes
[17] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	110
Units: Percentage of subjects
number (not applicable)
AEs	24.2	16.4
SAEs	4.8	0
MAEs	14.5	10.0
NDCMCs	0	0.9

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After any Primary Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After any Primary Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[18]

End point description

An AE was any untoward medical occurrence in a subject, temporally associated with the use of investigational product, whether or not considered related to the investigational product. SAE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalisation or prolongation of existing hospitalisation; was life-threatening; resulted in persistent disability/incapacity; congenital anomaly/birth defect and other important medical events. MAE was defined as a nonserious AE that resulted in an evaluation at a medical facility. NDCMC was defined as a disease or medical condition, not previously identified, that is expected to be persistent or otherwise long-lasting in its effects. Safety population included all randomised subjects who received at least 1 dose of investigational product and had safety data reported after vaccination.

End point type

Primary

End point timeframe

Within 30 Days after any primary Vaccination

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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	110
Units: Percentage of subjects
number (not applicable)
AEs	40.3	24.5
SAEs	6.5	0
MAEs	29.0	16.4
NDCMC	0	0.9

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs,MAEs and NDCMC Within 30 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With AEs, SAEs,MAEs and NDCMC Within 30 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[19]

End point description

End point type

Primary

End point timeframe

Within 30 Days after primary Vaccination 2

Notes
[19] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	42	109
Units: Percentage of subjects
number (not applicable)
AEs	33.3	12.8
SAEs	2.4	0
MAEs	23.8	11.0
NDCMC	0	0.9

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Primary Series Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Primary Series Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[20]

End point description

End point type

Primary

End point timeframe

From day of primary vaccination 1 at Day 1 up to 1 month after primary vaccination 2

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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	110
Units: Percentage of subjects
number (not applicable)
AEs	56.5	33.6
SAEs	6.5	1.8
MAEs	43.5	24.5
NDCMC	1.6	0.9

No statistical analyses for this end point

Primary: Percentage of Subjects With SAEs, MAEs and NDCMC Throughout Primary Series Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With SAEs, MAEs and NDCMC Throughout Primary Series Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[21]

End point description

End point type

Primary

End point timeframe

From the date of primary vaccination 1 up to 8 months after primary vaccination 2

Notes
[21] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	110
Units: Percentage of subjects
number (not applicable)
AEs	59.7	40.0
SAEs	9.7	4.5
MAEs	45.2	30.0
NDCMC	1.6	1.8

No statistical analyses for this end point

Primary: Percentage of Subjects With SAEs, MAEs and NDCMC During Primary Series Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With SAEs, MAEs and NDCMC During Primary Series Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[22]

End point description

End point type

Primary

End point timeframe

From 1 month after primary vaccination 2 up to booster vaccination

Notes
[22] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	41	109
Units: Percentage of subjects
number (not applicable)
AEs	17.1	18.3
SAEs	4.9	2.8
MAEs	12.2	15.6
NDCMC	0	0.9

No statistical analyses for this end point

Primary: Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 2: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined

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End point title

Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 2: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined ^[23]

End point description

Immediate AEs were defined as AEs occurring within the first 30 minutes after investigational product administration. Safety population included all randomised subjects who received at least 1 dose of investigational product and had safety data reported after vaccination.

End point type

Primary

End point timeframe

Within 30 Minutes After Primary Vaccination 2

Notes
[23] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	42	109
Units: Percentage of subjects
number (not applicable)	0	0

No statistical analyses for this end point

Primary: Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 1: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined

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End point title

Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 1: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined ^[24]

End point description

End point type

Primary

End point timeframe

Within 30 Minutes After Primary Vaccination 1

Notes
[24] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	62	110
Units: Percentage of subjects
number (not applicable)	0	0

No statistical analyses for this end point

Primary: Number of Subjects With Local Reactions Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Number of Subjects With Local Reactions Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[25]

End point description

Local reactions included tenderness at injection site, redness and swelling and were recorded by subject’s parents/legal guardians in an electronic diary (e-diary). Redness and swelling were measured and recorded in caliper units. 1 caliper unit =0.5 centimeter (cm) and graded as mild: 0.5 to 2.0 cm, moderate: >2.0 to 7.0 cm and severe: >7.0 cm. Tenderness at injection site was graded as mild: hurt if gently touched, moderate: hurt if gently touched with crying and severe: caused limitation of limb movement. Exact 2-sided CI was based on the Clopper and Pearson method. Primary vaccination 2 safety population included all subjects who received the second dose of investigational product at Visit 3 and who had safety follow-up between Visit 3 and prior to Visit 4. Here, ‘N'=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 7 Days after booster vaccination

Notes
[25] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	0 ^[26]	92
Units: Subjects
Redness		38
Swelling		35
Tenderness at injection site		63

Notes
[26] - Subjects did not receive booster vaccination due to study termination.

No statistical analyses for this end point

Primary: Percentage of Subjects With Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[27]

End point description

Systemic events were recorded by subject’s parents/legal guardians in e-diary.Fever was defined as temperature >=38.0deg C, categorised as 38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Exact 2-sided CI based on Clopper and Pearson method.Decreased appetite categorised as Mild:decreased interest in eating, Moderate:decreased oral intake,Severe: refusal to feed. Drowsiness: Mild: Increased or prolonged sleeping bouts,Moderate: Slightly subdued interfering with daily activity,Severe; Disabling, not interested in usual daily activity.Irritability;Mild: Easily consolable, Moderate: requiring increased attention,Severe: Inconsolable; crying could not be comforted.Booster vaccination safety population included subjects who received booster dose of investigational product, had safety follow-up between Visit 5 and prior to Visit 6. Here,‘N’=subjects evaluable for this endpoint. No subjects received booster vaccination in Group 7 and 11 due to study termination.

End point type

Primary

End point timeframe

Within 7 Days after booster vaccination

Notes
[27] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 8 and 10 Combined
Number of subjects analysed	91
Units: Percentage of subjects
number (confidence interval 95%)
Fever: >=38.0°C	35.2 (25.4 to 45.9)
Fever: 38.0°C to 38.4°C	19.8 (12.2 to 29.4)
Fever: >38.4°C to 38.9°C	11.0 (5.4 to 19.3)
Fever: >38.9°C to 40.0°C	4.4 (1.2 to 10.9)
Fever: >40.0°C	0 (0.0 to 4.0)
Decreased appetite: Mild	17.6 (10.4 to 27.0)
Decreased appetite: Moderate	27.5 (18.6 to 37.8)
Decreased appetite: Severe	2.2 (0.3 to 7.7)
Irritability: Mild	22.0 (14.0 to 31.9)
Irritability: Moderate	42.9 (32.5 to 53.7)
Irritability: Severe	7.7 (3.1 to 15.2)
Drowsiness: Mild	26.4 (17.7 to 36.7)
Drowsiness: Moderate	18.7 (11.3 to 28.2)
Drowsiness: Severe	1.1 (0.0 to 6.0)
Use of antipyretic medication	63.7 (53.0 to 73.6)

No statistical analyses for this end point

Primary: Percentage of Subjects With Immediate AE After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With Immediate AE After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[28]

End point description

End point type

Primary

End point timeframe

Within 30 minutes after booster vaccination

Notes
[28] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	0 ^[29]	92
Units: Percentage of subjects
number (not applicable)		0

Notes
[29] - No subject received booster vaccination due to study termination.

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

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End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[30]

End point description

End point type

Primary

End point timeframe

From date of booster vaccination through 1 month after the booster vaccination

Notes
[30] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	0 ^[31]	92
Units: Percentage of subjects
number (not applicable)
AEs		27.2
SAEs		0
MAEs		92
NDCMC		0

Notes
[31] - No subject received a booster vaccination in these groups due to study termination.

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Throughout Booster Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Top of page

End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Throughout Booster Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[32]

End point description

End point type

Primary

End point timeframe

From date of booster vaccination up to 6 months after the booster vaccination

Notes
[32] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	0 ^[33]	92
Units: Percentage of subjects
number (not applicable)
AEs (n=37)		40.2
SAEs (n=2)		2.2
MAEs (n=23)		25.0
NDCMC (n=0)		0

Notes
[33] - No subject received a booster vaccination in these groups due to study termination.

No statistical analyses for this end point

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Top of page

End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined ^[34]

End point description

End point type

Primary

End point timeframe

From 1 month after booster vaccination up to 6 months after booster vaccination

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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 7 and 11 Combined	Group 8 and 10 Combined
Number of subjects analysed	0 ^[35]	92
Units: Percentage of Subjects
number (not applicable)
AEs (n=16)		17.4
SAEs (n=2)		2.2
MAEs (n=14)		15.2
NDCMC (n=0)		0

Notes
[35] - No subject received a booster vaccination in these groups due to study termination.

No statistical analyses for this end point

Secondary: hSBA Geometric Mean Titers (GMTs) for Each of the MenB Test Strains: 1 Month After Primary Vaccination 2 in Group 3 and 4 Combined Versus Group 5

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End point title

hSBA Geometric Mean Titers (GMTs) for Each of the MenB Test Strains: 1 Month After Primary Vaccination 2 in Group 3 and 4 Combined Versus Group 5 ^[36]

End point description

GMTs were calculated by exponentiating mean logarithm of titers and CIs were calculated by exponentiating confidence limits based on the Student t distribution for the mean logarithm of the titers. Post-primary vaccination 2 evaluable immunogenicity population: subjects randomized to study group of interest; eligible through Visit (V)4;received vaccine at V1 and V3;blood drawn for assay testing within required timeframes at V4; had at least 1 valid, determinate MenA, MenC, MenW, MenY, or MenB assay result at V4; received no prohibited vaccines/treatment and had no protocol deviations through V4. Here,’N’ signifies subjects evaluable for this end point; and 'n'=subjects evaluable for specified rows.

End point type

Secondary

End point timeframe

1 Month after primary Vaccination 2

Notes
[36] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 5 (120 μg rLP2086 +Nimenrix +PLP)	Group 3 and 4 Combined
Number of subjects analysed	35	45
Units: Titers
geometric mean (confidence interval 95%)
PMB80 (A22) n=30, 40	13.9 (10.8 to 18.0)	15.3 (12.1 to 19.3)
PMB2707 (B44) n=35, 45	13.4 (9.8 to 18.3)	25.0 (19.9 to 31.4)

No statistical analyses for this end point

Secondary: Percentage of Subjects With Local Reactions Within 7 Days After Each Primary Vaccination: Group 3, 4 and 5

Top of page

End point title

Percentage of Subjects With Local Reactions Within 7 Days After Each Primary Vaccination: Group 3, 4 and 5 ^[37]

End point description

Local reactions included pain at injection site, redness and swelling and were recorded by subjects in an electronic diary (e-diary). Redness and swelling were measured and recorded in caliper units. 1 caliper unit =0.5 centimeter (cm) and graded as mild: >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm and severe: >10.0 cm. Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity and severe: prevented daily activity. Percentage of subjects with local reactions at injection site on left arm were reported in this endpoint. Safety population included all randomised subjects who received at least 1 dose of investigational product and had safety data reported after vaccination.

End point type

Secondary

End point timeframe

Within 7 Days after primary Vaccination(Vac) 1 and 2

Notes
[37] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Number of subjects analysed	36	16	53
Units: Percentage of subjects
number (confidence interval 95%)
Vaccination 1:Redness:Mild(n=36,16,53)	27.8 (14.2 to 45.2)	18.8 (4.0 to 45.6)	13.2 (5.5 to 25.3)
Vacc1Redness:Moderate9n=36,16,53)	8.3 (1.8 to 22.5)	0 (0.0 to 20.6)	3.8 (0.5 to 13.0)
Vacc1Redness: Severe(n=36,16,53)	0 (0.0 to 9.7)	0 (0.0 to 20.6)	0 (0.0 to 6.7)
Vacc1:Swelling: Mild(n=36,16,53)	16.7 (6.4 to 32.8)	6.3 (0.2 to 30.2)	9.4 (3.1 to 20.7)
Vacc1:Swelling: Moderate(n=36,16,53)	11.1 (3.1 to 26.1)	12.5 (1.6 to 38.3)	5.7 (1.2 to 15.7)
Vacc1:Swelling: Severe(n=36,16,53)	0 (0. to 9.7)	0 (0.0 to 20.6)	0 (0.0 to 6.7)
Vac1Tenderness at inj.site:Mildn=36,16,53)	19.4 (8.2 to 36.0)	12.5 (1.6 to 38.3)	22.6 (12.3 to 36.2)
Vac1Tenderness at inj.site: Moderate(n=36,16,53)	16.0 (4.5 to 36.1)	41.7 (25.5 to 59.2)	18.8 (4.0 to 45.6)
Vac1Tenderness at inj.site: Severe(n=36,16,53)	0 (0.0 to 9.7)	0 (0.0 to 20.6)	1.9 (0.0 to 10.1)
Vac2RednessMild(n=21,16,52)	38.1 (18.1 to 61.6)	18.8 (4.0 to 45.6)	23.1 (12.5 to 36.8)
Vac2Redness Moderate(n=21,16,52)	4.8 (0.1 to 23.8)	0 (0.0 to 20.6)	3.8 (0.5 to 13.2)
Vac2Redness Severe(n=21,16,52)	0 (0.0 to 16.1)	0 (0.0 to 20.6)	0 (0.0 to 6.8)
Vac2Swelling Mild(n=21,16,52)	19.0 (5.4 to 41.9)	12.5 (1.6 to 38.3)	9.6 (3.2 to 21.0)
Vac2SwellingModerate(n=21,16,52)	0 (0.0 to 16.1)	12.5 (1.6 to 38.3)	1.9 (0.0 to 10.3)
Vac2SwellingSevere(n=21,16,52)	0 (0.0 to 16.1)	0 (0.0 to 20.6)	0 (0.0 to 6.8)
Vac2Tenderness at inj.siteMild(n=21,16,52)	28.6 (11.3 to 52.2)	12.5 (1.6 to 38.3)	32.7 (20.3 to 47.1)
Vac2Tenderness at inj.siteModerate(n=21,16,52)	9.5 (1.2 to 30.4)	18.8 (4.0 to 45.6)	17.3 (8.2 to 30.3)
Vac2Tenderness at inj.siteSevere(n=21,16,52)	0 (0.0 to 16.1)	6.3 (0.2 to 30.2)	1.9 (0.0 to 10.3)

No statistical analyses for this end point

Secondary: hSBA GMTs for Each of the MenB Test Strains: 1 Month After Booster Vaccination in Groups 3, 4 and 5

Top of page

End point title

hSBA GMTs for Each of the MenB Test Strains: 1 Month After Booster Vaccination in Groups 3, 4 and 5 ^[38]

End point description

GMTs were calculated by exponentiating the mean logarithm of the titers and CIs were calculated by exponentiating the confidence limits based on the Student t distribution for the mean logarithm of the titers. Post-primary vaccination 2 evaluable immunogenicity population=subjects randomised to study group of interest, eligible through Visit 4, ie, fulfilling all inclusion criteria and none of exclusion criteria at each visit where eligibility criteria are collected and confirmed,received investigational products at Visits 1 and 3 as randomized, blood drawn for assay testing within required time frames at Visit 4(1 month after primary vaccination 2 [window 28-42 days]),at least 1 valid,determinate MenA, MenC, MenW, MenY, or MenB assay result at Visit 4,received no prohibited vaccines or treatment through Visit 4 and no important protocol deviations through Visit 4. Here, 'Number of Subjects Analysed’= subjects evaluable for this end point.

End point type

Secondary

End point timeframe

1 month after booster vaccination

Notes
[38] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Number of subjects analysed	18	0 ^[39]	0 ^[40]
Units: Titers
geometric mean (confidence interval 95%)
PMB80 (A22)	21.8 (11.1 to 42.6)	( to )	( to )
PMB2707 (B44)	25.4 (12.6 to 51.1)	( to )	( to )

Notes
[39] - Group 4 had no serum samples collected after Booster vaccination due to study termination
[40] - Group 5 had no serum samples collected after Booster vaccination due to study termination

No statistical analyses for this end point

Secondary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Each Primary Vaccination: Group 3,4 and 5

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End point title

Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Each Primary Vaccination: Group 3,4 and 5 ^[41]

End point description

Systemic events were recorded by subject’s parents/legal guardians in e-diary. Fever was defined as temperature >=38.0 degrees (deg) Celsius(C) and was categorised as 38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Exact 2-sided CI was based on the Clopper and Pearson method. Decreased appetite was categorized as Grade 1:decreased interest in eating, Grade 2:decreased oral intake, Grade3: refusal to feed. Drowsiness: Grade 1 Increased or prolonged sleeping bouts,Grade2: Slightly subdued interfering with daily activity, Grade3; Disabling, not interested in usual daily activity. Irritability; Grade1: Easily consolable, Grade2: requiring increased attention,Grade 3: Inconsolable; crying could not be comforted. Primary vaccination 1 safety population included all randomised subjects who received the first dose of investigational product at Visit 1 and had safety follow-up between Visit 1 and prior to Visit 3.

End point type

Secondary

End point timeframe

Within 7 Days after primary Vaccination 1 and 2

Notes
[41] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Number of subjects analysed	36	16	53
Units: Percentage of subjects
number (confidence interval 95%)
Vac1 Fever≥38.0°C(n=36,16,53)	58.3 (40.8 to 74.5)	25.0 (7.3 to 52.4)	64.2 (49.8 to 76.9)
Vac1Fever38.0°C to 38.4°C(n=36,16,53)	30.6 (16.3 to 48.1)	18.8 (4.0 to 45.6)	35.8 (23.1 to 50.2)
Vac1Fever>38.4°C to 38.9°C(n=36,16,53)	27.8 (14.2 to 45.2)	6.3 (0.2 to 30.2)	17.0 (8.1 to 29.8)
Vac1Fever>38.9°C to 40.0°C(n=36,16,53)	0 (0.0 to 9.7)	0 (0.0 to 20.6)	11.3 (4.3 to 23.0)
Vac1Fever >40.0°C(n=36,16,53)	0 (0.0 to 9.7)	0 (0.0 to 20.6)	0 (0.0 to 6.7)
Vac1Decreased appetiteMild(n=36,16,53)	25.0 (12.1 to 42.2)	6.3 (0.2 to 30.2)	28.3 (16.8 to 42.3)
Vac1Decreased appetiteModerate(n=36,16,53)	22.2 (10.1 to 39.2)	43.8 (19.8 to 70.1)	34.0 (21.5 to 48.3)
Vac1DecreasedappetiteSevere(n=36,16,53)	2.8 (0.1 to 14.5)	0 (0.0 to 20.6)	3.8 (0.5 to 13.0)
Vac1IrritabilityMild(n=36,16,53)	16.7 (6.4 to 32.8)	6.3 (0.2 to 30.2)	5.7 (1.2 to 15.7)
Vac1IrritabilityModerate(n=36,16,53)	58.3 (40.8 to 74.5)	75.0 (47.6 to 92.7)	58.5 (44.1 to 71.9)
Vac1IrritabilitySevere(n=36,16,53)	8.3 (1.8 to 22.5)	6.3 (0.22 to 30.2)	13.2 (5.5 to 25.3)
Vac1DrowsinessMild(n=36,16,53)	36.1 (20.8 to 53.8)	37.5 (15.2 to 64.6)	49.1 (35.1 to 63.2)
Vac1DrowsinessModerate(n=36,16,53)	33.3 (18.6 to 51.0)	31.3 (11.0 to 58.7)	39.6 (26.5 to 54.0)
Vac1DrowsinessSever(n=36,16,53)	2.8 (0.1 to 14.5)	0 (0.0 to 20.6)	3.8 (0.5 to 13.0)
Use of antipyretic medication(n=36,16,53)	58.3 (40.8 to 74.5)	56.3 (29.9 to 80.2)	83.0 (70.2 to 91.9)
Vac2≥38.0°C(n=21,16,52)	52.4 (29.8 to 74.3)	50.0 (24.7 to 75.3)	67.3 (52.9 to 79.7)
Vac2 >38.0°C to 38.4°C(n=21,16,52)	23.8 (8.2 to 47.2)	25.0 (7.3 to 52.4)	28.8 (17.1 to 43.1)
Vac2 >>38.4°C to 38.9°C(n=21,16,52)	23.8 (8.2 to 47.2)	25.0 (7.3 to 52.4)	25.0 (14.0 to 38.9)
Vac2>>38.9°C to 40.0°C(n=21,16,52)	4.8 (0.1 to 23.8)	0 (0.0 to 20.6)	13.5 (5.6 to 25.8)
Vac2>40.0°C(n=21,16,52)	0 (0.0 to 16.1)	0 (0.0 to 20.6)	0 (0.0 to 6.8)
Vac2Decreased appetiteMild(n=21,16,52)	4.8 (0.1 to 23.8)	6.3 (0.2 to 30.2)	28.8 (17.1 to 43.1)
Vac2Decreased appetiteModerate(n=21,16,52)	28.6 (11.3 to 52.2)	50.0 (24.7 to 75.3)	38.5 (25.3 to 53.0)
Vac2Decreased appetiteSevere(n=21,16,52)	4.8 (0.1 to 23.8)	6.3 (0.2 to 30.2)	5.8 (1.2 to 15.9)
Vac2IrritabilityMild(n=21,16,52)	47.6 (25.7 to 70.2)	43.8 (19.8 to 70.1)	40.4 (27.0 to 54.9)
Vac2IrritabilityModerate(n=21,16,52)	23.8 (8.2 to 47.2)	12.5 (1.6 to 38.3)	28.8 (17.1 to 43.1)
Vac2IrritabilitySevere(n=21,16,52)	0 (0.0 to 16.1)	0 (0.0 to 20.6)	3.8 (0.5 to 13.2)
Vac2DrowsinessMild(n=21,16,52)	47.6 (25.7 to 70.2)	43.8 (19.8 to 70.1)	40.4 (27.0 to 54.9)
Vac2DrowsinessModertae(n=21,16,52)	23.8 (8.2 to 47.2)	12.5 (1.6 to 38.3)	28.8 (17.1 to 43.1)
Vac2DrowsinessSevere(n=21,16,52)	0 (0.0 to 16.1)	0 (0.0 to 20.6)	3.8 (0.5 to 13.2)
Vac2Use of antipyretic medication(n=21,16,52)	81.0 (58.1 to 94.6)	87.5 (61.7 to 98.4)	86.5 (74.2 to 94.4)

No statistical analyses for this end point

Secondary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC: Groups 3, 4 and 5

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End point title

Percentage of Subjects With AEs, SAEs, MAEs and NDCMC: Groups 3, 4 and 5 ^[42]

End point description

End point type

Secondary

End point timeframe

Within 30 Days after Each Vaccination

Notes
[42] - 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: This endpoint was analyzed only for specified reporting arms.

End point values	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Number of subjects analysed	36	16	53
Units: Percentage of subjects
number (not applicable)
AEs	52.8	68.8	60.4
SAEs	2.8	6.3	20.8
MAEs	47.2	62.5	47.2
NDCMC	6.3	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Systematic assessment(SA): local reactions/systemic events within 7 days after vaccination 1, 2 and booster vaccination; Non-systematic assessment: SAEs and other AEs from Day 1 up to 196 days after last study vaccination

Adverse event reporting additional description

Same event may appear as both AE and SAE but are distinct events. An event may be categorized as serious in 1 subject and non-serious in another, or a subject may have experienced both AE and non-SAE.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

v25.1

Reporting group title

Group 2 (MenABCWY)

Reporting group description

Reporting group title

Group 1 (MenABCWY +PLP)

Reporting group description

Reporting group title

Group 11 (MenABCWY +TLP)

Reporting group description

Reporting group title

Group 7 (MenABCWY +SLP)

Reporting group description

Reporting group title

Group 8 (Bexsero +Nimenrix +PLP)

Reporting group description

Reporting group title

Group 10 (Bexsero +Nimenrix)

Reporting group description

Infant subjects aged 2 months were administered a single intramuscular injection of 0.5 mL of Bexsero into the left thigh and 0.5 mL of Nimenrix into the right thigh at Day 1 (primary vaccination 1), Month 2 (primary vaccination 2) and at approximately 10 months after vaccination 1 (booster vaccination). All subjects received a single intramuscular injection of Prevenar 13 and Vaxelis into the right thigh at 2 and 4 months of age.

Reporting group title

Group 4 (60 μg rLP2086 +Nimenrix)

Reporting group description

Reporting group title

Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)

Reporting group description

Reporting group title

Group 5 (120 μg rLP2086 +Nimenrix +PLP)

Reporting group description

Serious adverse events	Group 2 (MenABCWY)	Group 1 (MenABCWY +PLP)	Group 11 (MenABCWY +TLP)	Group 7 (MenABCWY +SLP)	Group 8 (Bexsero +Nimenrix +PLP)	Group 10 (Bexsero +Nimenrix)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	1 / 12 (8.33%)	5 / 50 (10.00%)	1 / 55 (1.82%)	6 / 55 (10.91%)	1 / 16 (6.25%)	1 / 36 (2.78%)	11 / 53 (20.75%)
number of deaths (all causes)	0	0	0	1	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	1	0	0	0	0	0
Nervous system disorders
Myoclonus
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Sudden infant death syndrome
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Papilloedema
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	2 / 53 (3.77%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	2 / 50 (4.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	2 / 53 (3.77%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis bacillus
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Human herpesvirus 7 infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis bacterial
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 12 (8.33%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	2 / 55 (3.64%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Group 2 (MenABCWY)	Group 1 (MenABCWY +PLP)	Group 11 (MenABCWY +TLP)	Group 7 (MenABCWY +SLP)	Group 8 (Bexsero +Nimenrix +PLP)	Group 10 (Bexsero +Nimenrix)	Group 4 (60 μg rLP2086 +Nimenrix)	Group 3 (60 μg rLP2086 +Nimenrix +PLP/SLP)	Group 5 (120 μg rLP2086 +Nimenrix +PLP)
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 25 (100.00%)	23 / 23 (100.00%)	12 / 12 (100.00%)	50 / 50 (100.00%)	54 / 55 (98.18%)	55 / 55 (100.00%)	16 / 16 (100.00%)	36 / 36 (100.00%)	53 / 53 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 12 (8.33%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
General disorders and administration site conditions
Drug withdrawal syndrome
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Injection site swelling
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0
Injection site erythema
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Injection site pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Injection site mass
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0
Tenderness (TENDERNESS)
alternative assessment type: Systematic
subjects affected / exposed	20 / 25 (80.00%)	20 / 23 (86.96%)	8 / 12 (66.67%)	41 / 50 (82.00%)	41 / 55 (74.55%)	45 / 55 (81.82%)	8 / 16 (50.00%)	23 / 36 (63.89%)	35 / 53 (66.04%)
occurrences all number	38	40	8	62	86	104	14	39	58
Pyrexia (FEVER)
alternative assessment type: Systematic
subjects affected / exposed	19 / 25 (76.00%)	15 / 23 (65.22%)	7 / 12 (58.33%)	38 / 50 (76.00%)	32 / 55 (58.18%)	39 / 55 (70.91%)	10 / 16 (62.50%)	25 / 36 (69.44%)	42 / 53 (79.25%)
occurrences all number	40	27	7	60	44	66	13	39	75
Swelling (SWELLING)
alternative assessment type: Systematic
subjects affected / exposed	14 / 25 (56.00%)	10 / 23 (43.48%)	2 / 12 (16.67%)	26 / 50 (52.00%)	30 / 55 (54.55%)	31 / 55 (56.36%)	5 / 16 (31.25%)	13 / 36 (36.11%)	10 / 53 (18.87%)
occurrences all number	28	13	2	39	72	71	7	20	15
Vaccination site pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Swelling
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Pyrexia
subjects affected / exposed	2 / 25 (8.00%)	6 / 23 (26.09%)	0 / 12 (0.00%)	4 / 50 (8.00%)	3 / 55 (5.45%)	5 / 55 (9.09%)	0 / 16 (0.00%)	2 / 36 (5.56%)	4 / 53 (7.55%)
occurrences all number	2	7	0	4	3	5	0	2	5
Pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Mass
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Immune system disorders
Food allergy
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Seasonal allergy
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Milk allergy
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	1	1	0	1	0	1
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Respiratory symptom
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Bronchospasm
subjects affected / exposed	3 / 25 (12.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	3	0	0	0	0	1	0	0	0
Catarrh
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Bronchial hyperreactivity
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0
Stridor
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Psychiatric disorders
Irritability (IRRITABILITY)
alternative assessment type: Systematic
subjects affected / exposed	20 / 25 (80.00%)	22 / 23 (95.65%)	12 / 12 (100.00%)	49 / 50 (98.00%)	44 / 55 (80.00%)	49 / 55 (89.09%)	14 / 16 (87.50%)	32 / 36 (88.89%)	50 / 53 (94.34%)
occurrences all number	60	59	14	104	119	149	35	69	110
Irritability
subjects affected / exposed	0 / 25 (0.00%)	2 / 23 (8.70%)	1 / 12 (8.33%)	4 / 50 (8.00%)	3 / 55 (5.45%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	3	2	4	4	2	0	0	1
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
SARS-CoV-2 test positive
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Cardiac murmur
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0
Head injury
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	2 / 55 (3.64%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	2	1	0	0
Limb injury
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Sunburn
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Tibia fracture
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Craniocerebral injury
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	1	0	0	0	1	0	0	0	1
Foreign body
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Wound
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Congenital, familial and genetic disorders
Atrial septal defect
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Congenital skin disorder
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Patent ductus arteriosus
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Plagiocephaly
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	2 / 36 (5.56%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Odontogenic cyst
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Nervous system disorders
Hypersomnia (INCREASED SLEEP)
alternative assessment type: Systematic
subjects affected / exposed	18 / 25 (72.00%)	18 / 23 (78.26%)	10 / 12 (83.33%)	39 / 50 (78.00%)	44 / 55 (80.00%)	43 / 55 (78.18%)	12 / 16 (75.00%)	32 / 36 (88.89%)	50 / 53 (94.34%)
occurrences all number	43	41	11	72	88	94	25	57	102
Partial seizures
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 12 (8.33%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Motor developmental delay
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
External hydrocephalus
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Somnolence
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	2 / 12 (16.67%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Eye disorders
Lacrimation increased
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Gastrointestinal disorders
Faeces soft
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Constipation
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	2 / 55 (3.64%)	3 / 55 (5.45%)	1 / 16 (6.25%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	1	2	3	1	0	1
Diarrhoea
subjects affected / exposed	2 / 25 (8.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	3 / 55 (5.45%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	2	0	0	1	3	1	0	0	0
Infantile colic
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	1 / 16 (6.25%)	1 / 36 (2.78%)	3 / 53 (5.66%)
occurrences all number	0	1	0	1	0	0	1	1	3
Gingival cyst
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 25 (4.00%)	4 / 23 (17.39%)	0 / 12 (0.00%)	1 / 50 (2.00%)	2 / 55 (3.64%)	1 / 55 (1.82%)	0 / 16 (0.00%)	3 / 36 (8.33%)	0 / 53 (0.00%)
occurrences all number	1	4	0	1	2	1	0	3	0
Teething
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	3 / 55 (5.45%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	3	0	0	0
Stomatitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	1	0	0	1	0
Papule
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Miliaria
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
Erythema
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Dermatitis atopic
subjects affected / exposed	1 / 25 (4.00%)	2 / 23 (8.70%)	1 / 12 (8.33%)	1 / 50 (2.00%)	2 / 55 (3.64%)	2 / 55 (3.64%)	1 / 16 (6.25%)	1 / 36 (2.78%)	1 / 53 (1.89%)
occurrences all number	1	2	1	1	2	2	1	1	1
Erythema (REDNESS)
alternative assessment type: Systematic
subjects affected / exposed	13 / 25 (52.00%)	8 / 23 (34.78%)	4 / 12 (33.33%)	22 / 50 (44.00%)	31 / 55 (56.36%)	35 / 55 (63.64%)	6 / 16 (37.50%)	18 / 36 (50.00%)	19 / 53 (35.85%)
occurrences all number	23	10	4	34	61	68	7	27	23
Rash
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	1	0	1	0	1
Seborrhoeic dermatitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 12 (8.33%)	0 / 50 (0.00%)	1 / 55 (1.82%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	1	0	1	1	0	0	0
Urticaria
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Dermatitis diaper
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	1 / 12 (8.33%)	1 / 50 (2.00%)	0 / 55 (0.00%)	3 / 55 (5.45%)	0 / 16 (0.00%)	1 / 36 (2.78%)	1 / 53 (1.89%)
occurrences all number	1	1	1	1	0	3	0	1	1
Endocrine disorders
Precocious puberty
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Torticollis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	2 / 12 (16.67%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Acquired plagiocephaly
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	1 / 16 (6.25%)	0 / 36 (0.00%)	2 / 53 (3.77%)
occurrences all number	0	0	0	0	0	1	1	0	2
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 25 (8.00%)	2 / 23 (8.70%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	1 / 55 (1.82%)	0 / 16 (0.00%)	1 / 36 (2.78%)	1 / 53 (1.89%)
occurrences all number	2	3	0	0	2	1	0	1	1
Bronchiolitis
subjects affected / exposed	4 / 25 (16.00%)	2 / 23 (8.70%)	1 / 12 (8.33%)	3 / 50 (6.00%)	1 / 55 (1.82%)	3 / 55 (5.45%)	2 / 16 (12.50%)	3 / 36 (8.33%)	2 / 53 (3.77%)
occurrences all number	4	2	1	3	1	3	2	3	2
Bronchitis viral
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
COVID-19
subjects affected / exposed	3 / 25 (12.00%)	2 / 23 (8.70%)	1 / 12 (8.33%)	8 / 50 (16.00%)	5 / 55 (9.09%)	6 / 55 (10.91%)	1 / 16 (6.25%)	0 / 36 (0.00%)	4 / 53 (7.55%)
occurrences all number	3	2	1	8	5	6	1	0	4
Candida nappy rash
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Cellulitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Hand-foot-and-mouth disease
subjects affected / exposed	7 / 25 (28.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	3 / 55 (5.45%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	7	0	0	0	3	0	0	0	0
Gastroenteritis
subjects affected / exposed	8 / 25 (32.00%)	6 / 23 (26.09%)	0 / 12 (0.00%)	1 / 50 (2.00%)	4 / 55 (7.27%)	4 / 55 (7.27%)	0 / 16 (0.00%)	2 / 36 (5.56%)	1 / 53 (1.89%)
occurrences all number	9	7	0	1	5	6	0	2	1
Ear infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	2 / 36 (5.56%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0
Conjunctivitis
subjects affected / exposed	3 / 25 (12.00%)	4 / 23 (17.39%)	1 / 12 (8.33%)	1 / 50 (2.00%)	4 / 55 (7.27%)	4 / 55 (7.27%)	3 / 16 (18.75%)	0 / 36 (0.00%)	3 / 53 (5.66%)
occurrences all number	3	5	1	1	4	6	3	0	3
Herpangina
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	2 / 55 (3.64%)	1 / 55 (1.82%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	2	1	1	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	2 / 55 (3.64%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0
Laryngitis
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	2 / 50 (4.00%)	1 / 55 (1.82%)	2 / 55 (3.64%)	0 / 16 (0.00%)	2 / 36 (5.56%)	3 / 53 (5.66%)
occurrences all number	3	1	0	2	1	2	0	2	3
Influenza
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Impetigo
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Mumps
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Parvovirus B19 infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Otitis media acute
subjects affected / exposed	6 / 25 (24.00%)	4 / 23 (17.39%)	0 / 12 (0.00%)	1 / 50 (2.00%)	1 / 55 (1.82%)	2 / 55 (3.64%)	1 / 16 (6.25%)	2 / 36 (5.56%)	2 / 53 (3.77%)
occurrences all number	8	5	0	2	1	2	1	4	2
Nasopharyngitis
subjects affected / exposed	2 / 25 (8.00%)	5 / 23 (21.74%)	0 / 12 (0.00%)	3 / 50 (6.00%)	3 / 55 (5.45%)	5 / 55 (9.09%)	1 / 16 (6.25%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	2	8	0	3	4	5	1	0	1
Oral candidiasis
subjects affected / exposed	1 / 25 (4.00%)	1 / 23 (4.35%)	1 / 12 (8.33%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	1	2	0	0	0	0	0	0
Otitis externa
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Otitis media
subjects affected / exposed	4 / 25 (16.00%)	1 / 23 (4.35%)	1 / 12 (8.33%)	0 / 50 (0.00%)	0 / 55 (0.00%)	2 / 55 (3.64%)	2 / 16 (12.50%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	8	1	1	0	0	2	4	1	0
Pharyngitis
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	1 / 50 (2.00%)	1 / 55 (1.82%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	3	1	0	1	1	1	0	0	0
Pharyngotonsillitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
Pneumonia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	1 / 12 (8.33%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Respiratory tract infection
subjects affected / exposed	3 / 25 (12.00%)	2 / 23 (8.70%)	0 / 12 (0.00%)	0 / 50 (0.00%)	3 / 55 (5.45%)	1 / 55 (1.82%)	1 / 16 (6.25%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	3	2	0	0	3	1	1	0	0
Respiratory tract infection viral
subjects affected / exposed	5 / 25 (20.00%)	4 / 23 (17.39%)	1 / 12 (8.33%)	0 / 50 (0.00%)	2 / 55 (3.64%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	9	7	1	0	2	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0
Skin candida
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Skin infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Superinfection bacterial
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Upper respiratory tract infection
subjects affected / exposed	5 / 25 (20.00%)	4 / 23 (17.39%)	3 / 12 (25.00%)	7 / 50 (14.00%)	11 / 55 (20.00%)	11 / 55 (20.00%)	2 / 16 (12.50%)	6 / 36 (16.67%)	7 / 53 (13.21%)
occurrences all number	9	12	5	7	18	21	2	18	10
Tracheobronchitis
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	3 / 25 (12.00%)	1 / 23 (4.35%)	1 / 12 (8.33%)	0 / 50 (0.00%)	2 / 55 (3.64%)	3 / 55 (5.45%)	1 / 16 (6.25%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	3	2	1	0	4	4	4	0	1
Viral infection
subjects affected / exposed	2 / 25 (8.00%)	4 / 23 (17.39%)	1 / 12 (8.33%)	0 / 50 (0.00%)	1 / 55 (1.82%)	4 / 55 (7.27%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	6	5	1	0	2	4	0	0	1
Viraemia
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Vaccination site infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0
Suspected COVID-19
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	1 / 55 (1.82%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Tonsillitis
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	1 / 36 (2.78%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0
Vulvovaginitis
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Viral rash
subjects affected / exposed	3 / 25 (12.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	2 / 16 (12.50%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	3	0	0	1	0	0	2	0	0
Metabolism and nutrition disorders
Failure to thrive
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	2 / 55 (3.64%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0
Decreased appetite
subjects affected / exposed	0 / 25 (0.00%)	1 / 23 (4.35%)	2 / 12 (16.67%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	2 / 53 (3.77%)
occurrences all number	0	1	2	2	0	0	0	0	3
Lactose intolerance
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	0	1
Obesity
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	1 / 55 (1.82%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Iron deficiency
subjects affected / exposed	1 / 25 (4.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	0 / 50 (0.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Decreased appetite (DECREASED APPETITE)
alternative assessment type: Systematic
subjects affected / exposed	17 / 25 (68.00%)	18 / 23 (78.26%)	9 / 12 (75.00%)	38 / 50 (76.00%)	37 / 55 (67.27%)	41 / 55 (74.55%)	11 / 16 (68.75%)	25 / 36 (69.44%)	46 / 53 (86.79%)
occurrences all number	39	35	10	67	79	88	24	44	90
Weight gain poor
subjects affected / exposed	0 / 25 (0.00%)	0 / 23 (0.00%)	0 / 12 (0.00%)	1 / 50 (2.00%)	0 / 55 (0.00%)	0 / 55 (0.00%)	0 / 16 (0.00%)	0 / 36 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

28 Jan 2021

Addition of observer-blind expanded enrollment stage to allow further safety evaluation while minimizing potential bias. Addition of corresponding safety/immunogenicity objectives and analysis triggering enrollment into this stage. Addition of a planned analysis 1 month after the booster vaccination in the open-label expanded-enrollment stage in lieu of the prior final analysis. Separated Bexsero randomization groups (Groups 8 and 10) from sentinel-cohort stepdown structure to allow enrollment into these groups at any time during the sentinel stage as vaccine assigned in these groups represents standard of care. Removed enrollment restrictions from these groups and applied fewer stopping rules.

13 Sep 2021

Implemented EDMC recommendations that resulted from an analysis of available fever and safety data and a review of paracetamol regimens following completion of enrollment to sentinel Group 5 (Trumenba 120 μg + Nimenrix + PLP).

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.

The study was not completed as initially designed due to study termination by the sponsor.

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Clinical trials

Clinical Trial Results: A Phase 2b Trial To Assess the Safety, Tolerability, And Immunogenicity of MenABCWY in Healthy Infants 2 and 6 Months of Age

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects Achieving hSBA Titer >=LLOQ for Each MenA, MenC, MenW and MenY Test Strains 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >=LLOQ for Each MenA, MenC, MenW and MenY Test Strains 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenACWY MenA, MenC, MenW and MenY Test Strains 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenACWY MenA, MenC, MenW and MenY Test Strains 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 3 and 4 Combined Versus Group 5

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each Neisseria Meningitidis Group B (MenB) Test Strain 1 Month After Primary Vaccination 2: Group 3 and 4 Combined Versus Group 5

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Groups 3, 4 and 5

Primary: Percentage of Subjects Achieving hSBA Titer >= LLOQ for Each MenB Test Strain 1 Month After Booster Vaccination: Groups 3, 4 and 5

Primary: Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Local Reactions Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After Primary Vaccination 1: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After any Primary Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Within 30 Days After any Primary Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs,MAEs and NDCMC Within 30 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs,MAEs and NDCMC Within 30 Days After Primary Vaccination 2: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Primary Series Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Primary Series Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With SAEs, MAEs and NDCMC Throughout Primary Series Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With SAEs, MAEs and NDCMC Throughout Primary Series Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With SAEs, MAEs and NDCMC During Primary Series Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With SAEs, MAEs and NDCMC During Primary Series Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 2: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined

Primary: Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 2: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined

Primary: Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 1: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined

Primary: Percentage of Subjects With Immediate AE Within 30 Minutes After Primary Vaccination 1: Groups 7 and 11 Combined Versus Groups 8 and 10 Combined

Primary: Number of Subjects With Local Reactions Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Number of Subjects With Local Reactions Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Immediate AE After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With Immediate AE After Booster Vaccination: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Vaccination Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Throughout Booster Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC Throughout Booster Stage: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Primary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC During Booster Follow-up Phase: Group 7 and 11 Combined Versus Group 8 and 10 Combined

Secondary: hSBA Geometric Mean Titers (GMTs) for Each of the MenB Test Strains: 1 Month After Primary Vaccination 2 in Group 3 and 4 Combined Versus Group 5

Secondary: hSBA Geometric Mean Titers (GMTs) for Each of the MenB Test Strains: 1 Month After Primary Vaccination 2 in Group 3 and 4 Combined Versus Group 5

Secondary: Percentage of Subjects With Local Reactions Within 7 Days After Each Primary Vaccination: Group 3, 4 and 5

Secondary: Percentage of Subjects With Local Reactions Within 7 Days After Each Primary Vaccination: Group 3, 4 and 5

Secondary: hSBA GMTs for Each of the MenB Test Strains: 1 Month After Booster Vaccination in Groups 3, 4 and 5

Secondary: hSBA GMTs for Each of the MenB Test Strains: 1 Month After Booster Vaccination in Groups 3, 4 and 5

Secondary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Each Primary Vaccination: Group 3,4 and 5

Secondary: Percentage of Subjects With Systemic Events and Antipyretic use Within 7 Days After Each Primary Vaccination: Group 3,4 and 5

Secondary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC: Groups 3, 4 and 5

Secondary: Percentage of Subjects With AEs, SAEs, MAEs and NDCMC: Groups 3, 4 and 5

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 2b Trial To Assess the Safety, Tolerability, And Immunogenicity of MenABCWY in Healthy Infants 2 and 6 Months of Age