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Clinical Trial Results:
A Phase II, Randomized, Double-Blind, Dosage, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Combined with Aluminum Hydroxide Adjuvant in Children, Toddlers, and Infants

Summary
EudraCT number	2014-000778-20
Trial protocol	FI Outside EU/EEA
Global end of trial date	20 Jun 2018

Results information
Results version number	v1(current)
This version publication date	27 Jan 2019
First version publication date	27 Jan 2019
Other versions

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

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Trial information

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Sponsor protocol code

NOR-202

ISRCTN number

US NCT number

NCT02153112

WHO universal trial number (UTN)

Sponsor organisation name

Takeda Vaccine, Inc.

Sponsor organisation address

One Takeda Parkway, Deerfield, IL, United States, 60015

Public contact

Medical Director, Takeda, +1 8778253327, trialdisclosures@takeda.com

Scientific contact

Medical Director, Takeda, +1 8778253327, trialdisclosures@takeda.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001609-PIP01-14

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?

Analysis stage

Final

Date of interim/final analysis

20 Jun 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

20 Jun 2018

Was the trial ended prematurely?

Main objective of the trial

The main objective of the trial is to select the optimal formulation of the norovirus vaccine from different concentrations of virus-like particles (VLP) combined with aluminum hydroxide for further development in children.

Protection of trial subjects

All study participants or their guardians were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Jun 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Colombia: 349

Country: Number of subjects enrolled

Finland: 128

Country: Number of subjects enrolled

Panama: 363

Worldwide total number of subjects

840

EEA total number of subjects

128

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)

480

Children (2-11 years)

360

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Participants took part in the study at 12 investigative sites in Finland, Panama, and Colombia from 23 June 2015 to 20 June 2018.

Screening details

Healthy volunteers (children, toddlers and infants) were enrolled to receive either one, two or three doses of 4 formulation of norovirus GI.1/GII4 bivalent virus like particle (VLP) vaccine.

Period 1 title

Overall Study

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

Cohort 1, Group 1: 1 Dose

Arm description

Children 4 to <9 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent virus-like particle (VLP) vaccine, intramuscularly (IM) and 500 µg aluminum hydroxide on Day 1, followed by placebo matching norovirus bivalent VLP vaccine IM on Day 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Single dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent virus-like particle (VLP) vaccine and 500 µg aluminum hydroxide on Day 1, followed by placebo matching norovirus bivalent VLP vaccine on Day 29.

Cohort 1, Group 1: 2 Doses

Arm description

Children 4 to <9 years of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide IM on Days 1 and 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent virus-like particle (VLP) vaccine and 500 µg aluminum hydroxide on Day 1, followed by placebo matching norovirus bivalent VLP vaccine on Day 29.

Cohort 1, Group 2: 1 Dose

Arm description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo-matching norovirus bivalent VLP vaccine, IM on Day 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2: 2 Doses

Arm description

Children 1 to <4 years of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2a: 1 Dose

Arm description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2a: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 3: 1 Dose

Arm description

Toddlers 6 months to <1 year of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 3: 2 Doses

Arm description

Toddlers 6 months to <1 year of age received 2 doses either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 2, Group 4: 2 Doses

Arm description

Infants 6 weeks to <6 months of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) formulations of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 56, followed by placebo-matching norovirus bivalent VLP vaccine, IM on Day 112.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) formulations of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide on Days 1 and 56, followed by placebo-matching norovirus bivalent VLP vaccine on Day 112.

Cohort 2, Group 4: 3 Doses

Arm description

Infants 6 weeks to <6 months of age received 3 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1, 56 and 112.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

3 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide on Days 1, 56 and 112.

Number of subjects in period 1	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Started	61	59	61	59	60	60	60	60	180	180
Completed	57	57	58	57	57	58	52	58	165	166
Not completed	4	2	3	2	3	2	8	2	15	14
Consent withdrawn by subject	3	1	2	2	1	1	7	2	13	12
Adverse event, non-fatal	-	-	1	-	-	-	-	-	-	-
Lost to follow-up	1	1	-	-	2	1	1	-	1	1
Reason not Specified	-	-	-	-	-	-	-	-	1	1

Period 2 title

Intermediate Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

Cohort 1, Group 1: 1 Dose

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 1: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2: 1 Dose

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2a: 1 Dose

Arm description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2a: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 3: 1 Dose

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 3: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 2, Group 4: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 2, Group 4: 3 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Number of subjects in period 2	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Started	57	57	58	57	57	58	52	58	165	166
Completed	54	54	55	57	52	56	52	56	144	162
Not completed	3	3	3	0	5	2	0	2	21	4
Missing full vaccine regimen/primary endpoint data	3	3	3	-	5	2	-	2	21	4

Period 3 title

Per-Protocol Period

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

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

Are arms mutually exclusive

Yes

Cohort 1, Group 1: 1 Dose

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 1: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2: 1 Dose

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2a: 1 Dose

Arm description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 2a: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 3: 1 Dose

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 1, Group 3: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 2, Group 4: 2 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Cohort 2, Group 4: 3 Doses

Arm description

Arm type

Experimental

Investigational medicinal product name

Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Baseline characteristics were collected for the per-protocol set.

Number of subjects in period 3 ^[2]	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Started	54	54	55	57	52	56	52	56	144	162
Completed	54	54	55	57	52	56	52	56	144	162

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Baseline characteristics were collected for the per-protocol set.

Baseline characteristics

Top of page

Reporting group title

Cohort 1, Group 1: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 1: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 2: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2a: 1 Dose

Reporting group description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Reporting group title

Cohort 1, Group 2a: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 3: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 3: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 3 Doses

Reporting group description

Reporting group values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses	Total
Number of subjects	54	54	55	57	52	56	52	56	144	162	742
Age, Customized
Units: Subjects
Infants and Toddlers (28 days-23 months)	0	0	17	19	15	14	52	56	144	162	479
Children (2-11 years)	54	54	38	38	37	42	0	0	0	0	263
Age Continuous
Units: years
arithmetic mean (full range (min-max))	5.9 (4 to 8)	5.8 (4 to 8)	2.1 (1 to 3)	2.1 (1 to 3)	1.9 (1 to 3)	2.1 (1 to 3)	8.3 (6 to 11)	7.9 (6 to 11)	3.1 (1 to 5)	3.0 (1 to 5)	-
Sex: Female, Male
Units: Subjects
Female	32	24	27	25	28	19	24	27	77	72	355
Male	22	30	28	32	24	37	28	29	67	90	387
Race/Ethnicity, Customized
Units: Subjects
Hispanic or Latino	26	24	26	29	52	56	52	56	144	162	627
Not Hispanic or Latino	28	30	28	27	0	0	0	0	0	0	113
Not Reported	0	0	1	1	0	0	0	0	0	0	2
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	18	19	9	9	11	10	24	29	69	75	273
Asian	0	0	0	0	0	0	1	0	0	0	1
Black or African American	2	1	0	0	8	10	7	5	16	24	73
Native Hawaiian or Other Pacific Islanders	0	0	0	0	0	0	1	0	0	0	1
White	28	30	28	27	0	2	2	0	1	3	121
Multiracial	0	0	1	1	0	0	0	0	0	0	2
Other	6	4	17	20	33	34	17	22	58	60	271
Height
Units: cm
arithmetic mean (full range (min-max))	117.4 (92 to 138)	116.5 (96 to 138)	89.9 (67 to 105)	89.8 (73 to 104)	89.7 (74 to 117)	89.9 (72 to 110)	70.6 (63 to 80)	69.3 (64 to 75)	60.2 (50 to 71)	60.2 (51 to 68)	-
Weight
Units: kg
arithmetic mean (full range (min-max))	22.41 (13.7 to 43.2)	22.19 (13.6 to 45.3)	13.55 (8.0 to 19.4)	13.39 (10.0 to 18.6)	13.19 (8.8 to 17.5)	13.11 (8.9 to 21.8)	9.02 (6.0 to 14.0)	8.85 (6.2 to 11.1)	6.33 (3.5 to 9.5)	6.35 (3.4 to 9.5)	-

End points

Top of page

Reporting group title

Cohort 1, Group 1: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 1: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 2: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2a: 1 Dose

Reporting group description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Reporting group title

Cohort 1, Group 2a: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 3: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 3: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 3 Doses

Reporting group description

Reporting group title

Cohort 1, Group 1: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 1: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 2: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2a: 1 Dose

Reporting group description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Reporting group title

Cohort 1, Group 2a: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 3: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 3: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 3 Doses

Reporting group description

Reporting group title

Cohort 1, Group 1: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 1: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 2: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2a: 1 Dose

Reporting group description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Reporting group title

Cohort 1, Group 2a: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 3: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 3: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 3 Doses

Reporting group description

Primary: Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 1

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End point title

Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 1 ^[1]

End point description

Seroresponse was defined as 4-fold rise or greater at Day 57 in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA). Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Primary

End point timeframe

Day 57

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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55
Units: percentage of participants
number (confidence interval 95%)	77.4 (63.8 to 87.7)	63.5 (49.0 to 76.4)	74.5 (60.4 to 85.7)	85.7 (73.8 to 93.6)	53.2 (38.1 to 67.9)	70.4 (56.4 to 82.0)	71.4 (56.7 to 83.4)	92.7 (82.4 to 98.0)

No statistical analyses for this end point

Primary: Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 2

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End point title

Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 2 ^[2]

End point description

Seroresponse was defined as 4-fold rise or greater at Day 140 in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA). Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Primary

End point timeframe

Day 140

Notes
[2] - 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: Statistical analysis was not available for this endpoint.

End point values	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	131	146
Units: percentage of participants
number (confidence interval 95%)	57.3 (48.3 to 65.9)	84.9 (78.1 to 90.3)

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1 ^[3]

End point description

Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination. Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Primary

End point timeframe

Day 1 after either of the vaccination given on Days 1, 29, 56 or 112

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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	61	59	61	59	60	60	60	60	180	179
Units: percentage of participants
number (not applicable)
Any solicited local AEs	52.5	66.1	34.4	45.8	26.7	30.0	11.7	13.3	22.2	30.7
Pain	52.5	66.1	34.4	35.6	26.7	25.0	8.3	13.3	22.2	28.5
Erythema	0	1.7	1.6	0	0	1.7	3.3	0	1.1	2.8
Induration	1.6	1.7	0	1.7	0	1.7	1.7	0	0	0
Swelling	0	5.1	0	0	0	1.7	0	0	0.6	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2 ^[4]

End point description

End point type

Primary

End point timeframe

Day 1 after either of the vaccination given on Days 1, 29, 56 or 112

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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	60	58	61	59	60	60	58	59	176	178
Units: percentage of participants
number (not applicable)
Any solicited local AEs	41.0	44.1	8.2	25.4	13.3	15.0	10.0	5.0	13.3	14.5
Pain	41.7	44.8	6.6	23.7	13.3	13.3	6.9	5.1	13.6	14.6
Erythema	0	0	3.3	5.1	0	0	1.7	0	0.6	0
Induration	0	0	0	1.7	0	1.7	0	0	0	0
Swelling	0	0	0	1.7	0	1.7	1.7	0	0.6	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3 ^[5]

End point description

End point type

Primary

End point timeframe

Day 3 after either of the vaccination given on Days 1, 29, 56 or 112

Notes
[5] - 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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	60	58	61	59	60	60	58	59	176	178
Units: percentage of participants
number (not applicable)
Any solicited local AEs	13.1	15.3	4.9	20.3	10.0	10.0	5.0	6.7	2.2	5.0
Pain	13.3	15.5	4.9	20.3	10.0	8.3	3.4	6.8	2.3	5.1
Erythema	0	0	1.6	3.4	0	0	0	0	0	0
Induration	0	0	1.6	0	0	1.7	0	0	0	0
Swelling	0	0	1.6	3.4	0	1.7	1.7	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4 ^[6]

End point description

End point type

Primary

End point timeframe

Day 4 after either of the vaccination given on Days 1, 29, 56 or 112

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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	60	58	61	59	60	60	58	59	176	178
Units: percentage of participants
number (not applicable)
Any solicited local AEs	6.6	6.8	1.6	11.9	6.7	10.0	6.7	6.7	3.3	4.5
Pain	6.7	6.9	0	11.9	6.7	6.7	5.2	6.8	3.4	4.5
Erythema	0	0	1.6	0	0	0	0	0	0	0
Induration	0	0	1.6	1.7	0	1.7	1.7	0	0	0
Swelling	0	0	0	0	0	1.7	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5 ^[7]

End point description

End point type

Primary

End point timeframe

Day 5 after either of the vaccination given on Days 1, 29, 56 or 112

Notes
[7] - 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: Statistical analysis was not performed for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	60	58	61	59	60	60	58	59	176	178
Units: percentage of participants
number (not applicable)
Any solicited local AEs	0	5.1	1.6	5.1	3.3	1.7	3.3	8.3	1.7	2.8
Pain	0	5.2	0	5.1	3.3	1.7	3.4	8.5	1.7	2.8
Erythema	0	0	1.6	0	0	0	0	0	0	0
Induration	0	0	1.6	1.7	0	0	0	0	0	0
Swelling	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6 ^[8]

End point description

End point type

Primary

End point timeframe

Day 6 after either of the vaccination given on Days 1, 29, 56 or 112

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: Statistical analysis was not performed for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	60	58	61	59	60	60	58	59	176	179
Units: percentage of participants
number (not applicable)
Any solicited local AEs	3.3	3.4	0	3.4	1.7	1.7	1.7	5.0	1.1	4.5
Pain	3.3	3.4	0	3.4	1.7	1.7	1.7	5.1	0.6	4.5
Erythema	0	0	0	0	0	0	0	0	0	0
Induration	0	0	0	1.7	0	0	0	1.7	0	0
Swelling	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7

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End point title

Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7 ^[9]

End point description

End point type

Primary

End point timeframe

Day 7 after either of the vaccination given on Days 1, 29, 56 or 112

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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	60	58	61	59	60	60	58	59	176	178
Units: percentage of participants
number (not applicable)
Any solicited local AEs	1.6	3.4	0	1.7	1.7	1.7	1.7	3.3	0.6	2.2
Pain	1.7	3.4	0	1.7	1.7	1.7	1.7	3.4	0.6	2.2
Erythema	0	0	0	0	0	0	0	0	0	0
Induration	0	0	0	0	0	0	0	0	0	0
Swelling	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary–Recorded) Following Either Vaccination

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End point title

Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary–Recorded) Following Either Vaccination ^[10]

End point description

Systemic AEs are defined as headache, fatigue, myalgia, arthralgia, vomiting (number per day/intensity), and diarrhea (number per day/consistency) for children aged 4 to <9 years; and irritability/fussiness, drowsiness, loss of appetite, vomiting (number per day/intensity), and diarrhea (number per day/consistency) for children aged 6 weeks to <4 years on the day of vaccination and daily through Day 7 after each vaccination. Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

End point type

Primary

End point timeframe

Days 1 through 7 after each vaccination given on Days 1, 29, 56 or 112

Notes
[10] - 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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	61	59	61	59	60	60	60	60	180	179
Units: percentage of participants
number (not applicable)
Any solicited systemic AEs	50.8	61.0	44.3	54.2	41.7	43.3	56.7	50.0	60.0	59.2
Headache	21.7	25.9	0	0	0	0	0	0	0	0
Fatigue	23.3	29.3	0	0	0	0	0	0	0	0
Myalgia	26.7	24.1	0	0	0	0	0	0	0	0
Arthralgia	1.7	6.9	0	0	0	0	0	0	0	0
Vomiting	8.3	5.2	6.6	6.8	10.0	11.7	27.6	16.9	21.6	23.6
Diarrhea	6.9	10.7	13.1	23.7	18.3	18.3	31.0	25.4	31.8	30.9
Irritability/Fussiness	0	0	23.0	30.5	23.3	18.3	27.6	23.7	40.3	41.6
Drowsiness	0	0	16.4	22.0	23.3	21.7	22.4	20.3	33.5	33.1
Loss of Appetite	0	0	21.3	33.9	16.7	18.3	25.9	23.7	22.7	19.7

No statistical analyses for this end point

Primary: Body Temperature Through Day 7 Following Either Vaccination

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End point title

Body Temperature Through Day 7 Following Either Vaccination ^[11]

End point description

Body temperature measurement was performed using the thermometer provided by the site through Day 7 after each vaccination. The highest body temperature observed each day was recorded on the Diary Card. Body temperature is categorized as 1) Any (temperature 38°C or higher), 2) 38°C - <38.5°C, 3) 38.5°C - <39°C, 4) 39°C - <39.5°C, 5) 39.5°C - <40°C, 6) 40°C or higher. Number of participants with the particular body temperature is reported within the pre-defined categories. Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

End point type

Primary

End point timeframe

Post-vaccination approximately 30 minutes and 6 hours later, then daily through Day 7 after each vaccination given on Days 1, 29, 56 or 112

Notes
[11] - 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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	61	59	61	59	60	60	60	60	180	179
Units: participants
Any (temperature 38°C or higher)	2	6	7	5	6	8	8	11	26	23
38°C - <38.5°C	0	2	2	3	4	4	5	4	13	11
38.5°C - <39°C	1	2	3	2	1	3	3	2	12	7
39°C - <39.5°C	1	2	1	0	1	1	0	3	0	3
39.5°C - <40°C	0	0	0	0	0	0	0	2	1	2
40°C or higher	0	0	1	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose

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End point title

Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose ^[12]

End point description

Unsolicited AEs are any local or systemic AEs, as defined by this study, that are not solicited. Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

End point type

Primary

End point timeframe

Unsolicited AEs were collected within 28 days of all vaccinations (Day 1 to 57 for Cohort 1 and Day 1 to 140 for Cohort 2)

Notes
[12] - 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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	61	59	61	59	60	60	60	60	180	179
Units: percentage of participants
number (not applicable)	55.7	55.9	67.2	69.5	55.0	46.7	73.3	70.0	77.2	76.0

No statistical analyses for this end point

Primary: Percentage of Participants with Serious Adverse Events (SAEs)

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End point title

Percentage of Participants with Serious Adverse Events (SAEs) ^[13]

End point description

A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

End point type

Primary

End point timeframe

Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293

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: Statistical analysis was not available for this endpoint.

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	61	59	61	59	60	60	60	60	180	179
Units: percentage of participants
number (not applicable)	1.6	3.4	1.6	3.4	10.0	1.7	10.0	8.3	9.4	13.4

No statistical analyses for this end point

Secondary: Percentage of Participants with a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)

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End point title

Percentage of Participants with a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)

End point description

Seroresponse was defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-Like particle (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA). Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Here, overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55	138	150
Units: percentage of participants
number (confidence interval 95%)	88.7 (77.0 to 95.7)	82.7 (69.7 to 91.8)	92.2 (81.1 to 97.8)	92.9 (82.7 to 98.0)	78.7 (64.3 to 89.3)	94.4 (84.6 to 98.8)	95.9 (86.0 to 99.5)	100.0 (93.5 to 100.0)	94.9 (89.8 to 97.9)	98.0 (94.3 to 99.6)

No statistical analyses for this end point

Secondary: Percentage of Participants with a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)

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End point title

Percentage of Participants with a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)

End point description

Seroresponse was defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-Like particle (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA). Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55	134	150
Units: percentage of participants
number (confidence interval 95%)	81.1 (68.0 to 90.6)	69.2 (54.9 to 81.3)	76.5 (62.5 to 87.2)	87.5 (75.9 to 94.8)	63.8 (48.5 to 77.3)	72.2 (58.4 to 83.5)	75.5 (61.1 to 86.7)	92.7 (82.4 to 98.0)	58.2 (49.4 to 66.7)	86.0 (79.4 to 91.1)

No statistical analyses for this end point

Secondary: Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

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End point title

Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

End point description

Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55	144	162
Units: titer
geometric mean (confidence interval 95%)	6039.1 (4786.3 to 7619.9)	12907.6 (10875.5 to 15319.4)	2856.2 (2232.0 to 3654.9)	7350.8 (6208.6 to 8703.2)	3892.1 (2852.7 to 5310.3)	12623.8 (10074.0 to 15818.9)	1240.1 (948.3 to 1621.7)	7139.1 (5863.5 to 8692.2)	4121.1 (3688.4 to 4604.6)	11806.3 (10537.6 to 13227.8)

No statistical analyses for this end point

Secondary: Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

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End point title

Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

End point description

Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55	143	162
Units: titer
geometric mean (confidence interval 95%)	11057.9 (8257.3 to 14808.3)	10228.3 (8171.2 to 12803.3)	3293.0 (2220.5 to 4883.3)	7955.2 (6065.9 to 10433.0)	5950.6 (3927.2 to 9016.7)	10896.5 (8452.0 to 14048.0)	620.2 (383.7 to 1002.7)	3252.1 (2403.3 to 4400.7)	1316.2 (1103.9 to 1569.4)	3829.8 (3311.7 to 4428.9)

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

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End point title

Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

End point description

Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55	138	150
Units: ratio
geometric mean (confidence interval 95%)	19.22 (12.98 to 28.44)	43.55 (25.21 to 75.25)	44.11 (28.48 to 68.32)	89.95 (56.51 to 143.18)	13.01 (7.92 to 21.37)	43.99 (27.71 to 69.83)	47.45 (30.59 to 73.60)	276.41 (206.44 to 370.09)	34.11 (26.54 to 43.84)	122.80 (93.93 to 160.54)

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

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End point title

Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

End point description

Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	53	52	51	56	47	54	49	55	134	150
Units: ratio
number (confidence interval 95%)	7.46 (5.63 to 9.87)	10.00 (6.74 to 14.85)	10.87 (7.48 to 15.77)	19.20 (12.66 to 29.11)	5.62 (3.83 to 8.22)	11.93 (7.46 to 19.07)	9.54 (5.80 to 15.71)	55.73 (36.50 to 85.09)	7.85 (5.86 to 10.50)	23.55 (17.85 to 31.08)

No statistical analyses for this end point

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)

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End point title

Percentage of Participants with a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)

End point description

Percentage of participants with a 4-fold rise or greater in serum anti-norovirus antibody titers for both GI.1 VLP and GII.4 VLP as measured by histoblood group antigen (HBGA) binding assay. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	48	47	44	49	43	47	30	41	129	144
Units: percentage of participants
number (confidence interval 95%)	75.0 (60.4 to 86.4)	91.5 (79.6 to 97.6)	50.0 (34.6 to 65.4)	95.9 (86.0 to 99.5)	51.2 (35.5 to 66.7)	89.4 (76.9 to 96.5)	36.7 (19.9 to 56.1)	85.4 (70.8 to 94.4)	48.1 (39.2 to 57.0)	67.4 (59.1 to 74.9)

No statistical analyses for this end point

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)

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End point title

Percentage of Participants with a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)

End point description

The percentage of participants with a 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-like particle (VLP) as measured by HBGA binding assay. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	52	50	49	53	43	50	40	50	137	157
Units: percentage of participants
number (confidence interval 95%)	94.2 (84.1 to 98.8)	98.0 (89.4 to 99.9)	81.6 (68.0 to 91.2)	100.0 (93.3 to 100.0)	74.4 (58.8 to 86.5)	98.0 (89.4 to 99.9)	50.0 (33.8 to 66.2)	96.0 (86.3 to 99.5)	92.0 (86.1 to 95.9)	94.9 (90.2 to 97.8)

No statistical analyses for this end point

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)

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End point title

Percentage of Participants with a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)

End point description

The percentage of participants with a 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-like particle (VLP) as measured by HBGA binding assay. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	49	48	45	49	47	51	38	46	134	147
Units: percentage of participants
number (confidence interval 95%)	81.6 (68.0 to 91.2)	93.8 (82.8 to 98.7)	64.4 (48.8 to 78.1)	95.9 (86.0 to 99.5)	68.1 (52.9 to 80.9)	90.2 (78.6 to 96.7)	47.4 (31.0 to 64.2)	87.0 (73.7 to 95.1)	48.5 (39.8 to 57.3)	70.7 (62.7 to 78.0)

No statistical analyses for this end point

Secondary: Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)

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End point title

Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)

End point description

Blocking titers 50 (BT50) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	52	51	49	53	45	53	42	52	142	162
Units: titer
geometric mean (confidence interval 95%)	166.4 (136.0 to 203.6)	491.4 (397.1 to 608.1)	135.2 (106.5 to 171.7)	346.0 (297.5 to 402.3)	145.0 (108.6 to 193.8)	531.1 (424.0 to 665.2)	63.1 (45.3 to 87.9)	350.1 (273.7 to 447.9)	202.2 (180.7 to 226.2)	561.7 (499.2 to 632.1)

No statistical analyses for this end point

Secondary: Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)

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End point title

Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)

End point description

Blocking titers 50 (BT50) of anti-norovirus GII.4 VLP antibody titers as measured by HBGA binding assay. Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	50	49	46	51	47	54	43	51	136	150
Units: titer
geometric mean (confidence interval 95%)	982.1 (652.4 to 1478.4)	933.6 (678.3 to 1284.9)	197.1 (119.0 to 326.5)	514.8 (372.1 to 712.3)	444.6 (261.9 to 754.8)	721.8 (510.2 to 1021.1)	68.5 (44.1 to 106.4)	282.6 (194.8 to 410.0)	102.4 (83.1 to 126.1)	243.9 (203.3 to 292.8)

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)

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End point title

Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)

End point description

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	52	50	49	53	43	50	40	50	137	157
Units: ratio
geometric mean (confidence interval 95%)	8.93 (7.58 to 10.53)	23.07 (18.56 to 28.68)	7.22 (5.47 to 9.52)	22.15 (19.06 to 25.73)	6.10 (4.41 to 8.42)	24.21 (19.36 to 30.29)	3.68 (2.64 to 5.13)	20.01 (15.54 to 25.76)	11.48 (10.09 to 13.06)	32.03 (27.38 to 37.47)

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)

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End point title

Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)

End point description

End point type

Secondary

End point timeframe

Cohort 1: Day 57; Cohort 2: Day 140

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	49	48	45	49	47	51	38	46	134	147
Units: ratio
geometric mean (confidence interval 95%)	9.31 (6.93 to 12.52)	12.73 (9.60 to 16.90)	5.35 (3.94 to 7.28)	15.95 (12.31 to 20.66)	8.34 (5.01 to 13.87)	15.36 (11.26 to 20.96)	3.91 (2.60 to 5.88)	17.00 (11.66 to 24.80)	3.73 (2.84 to 4.90)	8.13 (6.39 to 10.35)

No statistical analyses for this end point

Secondary: Percentage of Participants with Any Adverse Event (AE) Leading to Withdrawal from the Study

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End point title

Percentage of Participants with Any Adverse Event (AE) Leading to Withdrawal from the Study

End point description

Withdrawal due to an AE will occur if the participant experiences an AE that requires early termination because continued participation imposes an unacceptable risk to the participant's health or the participant is unwilling to continue because of the AE. Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

End point type

Secondary

End point timeframe

Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293

End point values	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Number of subjects analysed	61	59	61	59	60	60	60	60	180	179
Units: percentage of participants
number (not applicable)	0	0	1.6	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Unsolicited AEs 28 days after each vaccination (Day 1 to 57 for Cohort 1 and Day 1 up to 140 for Cohort 2) and Serious Adverse Events (SAEs) throughout the trial (Up to Day 210 for Cohort 1 and Day 293 for Cohort 2)

Adverse event reporting additional description

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Cohort 1, Group 1: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 1: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 2: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 2a: 1 Dose

Reporting group description

Children 1 to <4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.

Reporting group title

Cohort 1, Group 2a: 2 Doses

Reporting group description

Reporting group title

Cohort 1, Group 3: 1 Dose

Reporting group description

Reporting group title

Cohort 1, Group 3: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 2 Doses

Reporting group description

Reporting group title

Cohort 2, Group 4: 3 Doses

Reporting group description

Serious adverse events	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 61 (1.64%)	2 / 59 (3.39%)	1 / 61 (1.64%)	2 / 59 (3.39%)	6 / 60 (10.00%)	1 / 60 (1.67%)	6 / 60 (10.00%)	5 / 60 (8.33%)	17 / 180 (9.44%)	24 / 179 (13.41%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Burns Third Degree
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Gastrointestinal disorders
Enteritis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (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	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	0 / 0
Incarcerated Inguinal Hernia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 180 (0.00%)	0 / 179 (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	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	0 / 0
Intussusception
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Reproductive system and breast disorders
Testicular Torsion
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthmatic Crisis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	2 / 60 (3.33%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	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	0 / 0
Asthma
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 61 (1.64%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	2 / 60 (3.33%)	2 / 60 (3.33%)	6 / 180 (3.33%)	9 / 179 (5.03%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 2	0 / 2	0 / 7	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue Fever
subjects affected / exposed	0 / 61 (0.00%)	2 / 59 (3.39%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	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	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 61 (1.64%)	0 / 59 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	1 / 60 (1.67%)	0 / 60 (0.00%)	2 / 180 (1.11%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 2	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	0 / 0
Furuncle
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	1 / 59 (1.69%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (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	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	0 / 0
Atypical Pneumonia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Otitis Media Acute
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Viral Upper Respiratory Tract Infection
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	2 / 60 (3.33%)	0 / 60 (0.00%)	2 / 180 (1.11%)	4 / 179 (2.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tracheitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Gastroenteritis Viral
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 180 (0.00%)	0 / 179 (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	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	0 / 0
Urinary Tract Infection
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 60 (1.67%)	0 / 180 (0.00%)	4 / 179 (2.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Croup Infectious
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Gastroenteritis Bacterial
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0
Muscle Abscess
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	0 / 179 (0.00%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Subcutaneous Abscess
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	1 / 180 (0.56%)	2 / 179 (1.12%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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	0 / 0
Pneumonia Respiratory Syncytial Viral
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	2 / 179 (1.12%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Encephalitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Periorbital Cellulitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0
Pneumonia Bacterial
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	1 / 179 (0.56%)
occurrences causally related to treatment / all	0 / 0	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	0 / 0

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

Non-serious adverse events	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 61 (40.98%)	27 / 59 (45.76%)	28 / 61 (45.90%)	32 / 59 (54.24%)	21 / 60 (35.00%)	19 / 60 (31.67%)	36 / 60 (60.00%)	35 / 60 (58.33%)	119 / 180 (66.11%)	122 / 179 (68.16%)
Nervous system disorders
Headache
subjects affected / exposed	2 / 61 (3.28%)	5 / 59 (8.47%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	2	5	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 61 (0.00%)	4 / 59 (6.78%)	4 / 61 (6.56%)	3 / 59 (5.08%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	6 / 180 (3.33%)	10 / 179 (5.59%)
occurrences all number	0	5	4	3	0	0	0	0	6	10
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	9 / 180 (5.00%)	3 / 179 (1.68%)
occurrences all number	0	0	0	0	0	0	0	0	9	3
Gastrointestinal disorders
Abdominal Pain Upper
subjects affected / exposed	3 / 61 (4.92%)	8 / 59 (13.56%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	3	8	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 61 (0.00%)	3 / 59 (5.08%)	3 / 61 (4.92%)	3 / 59 (5.08%)	0 / 60 (0.00%)	0 / 60 (0.00%)	5 / 60 (8.33%)	2 / 60 (3.33%)	10 / 180 (5.56%)	15 / 179 (8.38%)
occurrences all number	0	4	3	4	0	0	5	2	12	16
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
subjects affected / exposed	4 / 61 (6.56%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	4	0	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	2 / 61 (3.28%)	5 / 59 (8.47%)	4 / 61 (6.56%)	5 / 59 (8.47%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	3	6	4	5	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis Diaper
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	11 / 180 (6.11%)	18 / 179 (10.06%)
occurrences all number	0	0	0	0	0	0	0	0	15	19
Infections and infestations
Nasopharyngitis
subjects affected / exposed	15 / 61 (24.59%)	7 / 59 (11.86%)	5 / 61 (8.20%)	8 / 59 (13.56%)	14 / 60 (23.33%)	10 / 60 (16.67%)	23 / 60 (38.33%)	24 / 60 (40.00%)	86 / 180 (47.78%)	92 / 179 (51.40%)
occurrences all number	19	7	6	10	15	12	28	30	138	131
Upper Respiratory Tract Infection
subjects affected / exposed	1 / 61 (1.64%)	4 / 59 (6.78%)	8 / 61 (13.11%)	7 / 59 (11.86%)	0 / 60 (0.00%)	0 / 60 (0.00%)	4 / 60 (6.67%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	1	4	12	8	0	0	4	0	0	0
Rhinitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	5 / 61 (8.20%)	4 / 59 (6.78%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	0	0	6	4	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	4 / 61 (6.56%)	2 / 59 (3.39%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	8 / 180 (4.44%)	7 / 179 (3.91%)
occurrences all number	0	0	5	3	0	0	0	0	8	8
Otitis Media
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	4 / 61 (6.56%)	5 / 59 (8.47%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	0	0	6	5	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	5 / 60 (8.33%)	5 / 60 (8.33%)	2 / 60 (3.33%)	3 / 60 (5.00%)	15 / 180 (8.33%)	11 / 179 (6.15%)
occurrences all number	0	0	0	0	5	6	2	4	15	11
Viral Infection
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	2 / 60 (3.33%)	1 / 60 (1.67%)	1 / 60 (1.67%)	5 / 60 (8.33%)	11 / 180 (6.11%)	11 / 179 (6.15%)
occurrences all number	0	0	0	0	2	1	1	5	11	13
Pharyngitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	3 / 60 (5.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0
Acarodermatitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	4 / 60 (6.67%)	1 / 60 (1.67%)	2 / 180 (1.11%)	5 / 179 (2.79%)
occurrences all number	0	0	0	0	0	0	4	1	2	5
Pyoderma
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	3 / 60 (5.00%)	0 / 60 (0.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0
Pharyngotonsillitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	2 / 60 (3.33%)	3 / 60 (5.00%)	0 / 180 (0.00%)	0 / 179 (0.00%)
occurrences all number	0	0	0	0	0	0	3	3	0	0
Bronchiolitis
subjects affected / exposed	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 61 (0.00%)	0 / 59 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	0 / 60 (0.00%)	9 / 180 (5.00%)	7 / 179 (3.91%)
occurrences all number	0	0	0	0	0	0	0	0	10	7

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Were there any global substantial amendments to the protocol? Yes

07 Nov 2014

Amended to revise the study design as follows: • The age stratification was modified. • The number of blood draws for Cohort 1 was reduced from 5 to 4 and for Cohort 2 was reduced from 7 to 5. • The number of formulation arms was reduced from 11 to 8 based on data from the adult trial, NOR-107. • Assessed avidity of anti-norovirus VLP antibodies by age, dose and regimen. • A licensed benefit vaccine was mentioned to be offered to all participants after trial exit.

26 Mar 2015

Amended to change the trial design with regard to the down selection of formulations based on additional data from the adult trial NOR-107. Specifically, the new antibody data from trial NOR-107 resulted in similar immunogenicity and safety in adults administered the trial vaccine both with and without the MPL adjuvant when combined with Al(OH)3 adjuvant. Therefore, the decision was made to evaluate the trial vaccine with the Al(OH)3 adjuvant alone in subjects enrolled in trial NOR-202. Therefore, the number of formulation arms in this study has been further reduced from eight to four.

01 Mar 2016

Amended to enroll an additional 120 children (1 to < 4 years; designated Group 2a) in order to asess the safety and immunogenicity of the recently manufactured NoV vaccine in a similar age group to Group 2.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase II, Randomized, Double-Blind, Dosage, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Combined with Aluminum Hydroxide Adjuvant in Children, Toddlers, and Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 1

Primary: Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 1

Primary: Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 2

Primary: Percentage of Participants with a Seroresponse (Pan-Ig ELISA) in Cohort 2

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7

Primary: Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7

Primary: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary–Recorded) Following Either Vaccination

Primary: Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary–Recorded) Following Either Vaccination

Primary: Body Temperature Through Day 7 Following Either Vaccination

Primary: Body Temperature Through Day 7 Following Either Vaccination

Primary: Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose

Primary: Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose

Primary: Percentage of Participants with Serious Adverse Events (SAEs)

Primary: Percentage of Participants with Serious Adverse Events (SAEs)

Secondary: Percentage of Participants with a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)

Secondary: Percentage of Participants with a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)

Secondary: Percentage of Participants with a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)

Secondary: Percentage of Participants with a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)

Secondary: Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)

Secondary: Percentage of Participants with a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)

Secondary: Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)

Secondary: Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)

Secondary: Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)

Secondary: Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)

Secondary: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)

Secondary: Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)

Secondary: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)

Secondary: Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)

Secondary: Percentage of Participants with Any Adverse Event (AE) Leading to Withdrawal from the Study

Secondary: Percentage of Participants with Any Adverse Event (AE) Leading to Withdrawal from the Study

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Randomized, Double-Blind, Dosage, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Combined with Aluminum Hydroxide Adjuvant in Children, Toddlers, and Infants