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    Clinical Trial Results:
    A Phase II, Randomized, Controlled, Double-Blind, Dosage and Adjuvant Justification, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Adjuvanted with or without Monophosphoryl Lipid A and Aluminum Hydroxide in Adolescents and Adults

    Summary
    EudraCT number
    2013-001419-64
    Trial protocol
    BE  
    Global end of trial date
    19 Jun 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    04 Jul 2016
    First version publication date
    04 Jul 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NOR-107
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02038907
    WHO universal trial number (UTN)
    U1111-1147-3239
    Sponsors
    Sponsor organisation name
    Takeda Development Center Americas, Inc.
    Sponsor organisation address
    One Takeda Parkway, Deerfield, IL, United States, 60015
    Public contact
    Director, Clinical Science, Takeda, +1 877-825-3327, trialdisclosures@takeda.com
    Scientific contact
    Director, Clinical Science, Takeda, +1 877-825-3327, trialdisclosures@takeda.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Jun 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Jun 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Jun 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to select the optimal formulation of the norovirus vaccine from different concentrations of virus-like particles (VLP) and MPL adjuvant (3-O-desacyl-4’-monophosphoryl lipid A) for further development.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Mar 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 420
    Worldwide total number of subjects
    420
    EEA total number of subjects
    420
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    420
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants took part in the study at 2 investigative sites in Belgium from 28 March 2014 (first participants signed the informed consent form) to 19 June 2015.

    Pre-assignment
    Screening details
    Healthy volunteers were enrolled equally in 1 of 14 unique formulation treatment groups: 11 formulation arms received 1 dose and 3 formulation arms received 2 doses.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    GI.1/GII.4 (15/15) - MPL (50)
    Arm description
    Hepatitis A vaccine, intramuscular (IM), on Day 1, followed by norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus virus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MLP) and 500 µg aluminum hydroxide, IM on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/50) - MPL (50)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (50/50) - MPL (50)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/15) - MPL (15)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/50) - MPL (15)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (50/50) - MPL (15)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/15)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/50)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (50/50)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (50/150)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/50) - Al(OH)3 (167)
    Arm description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Hepatitis A Vaccine
    Investigational medicinal product code
    Other name
    Havrix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Hepatitis A vaccine, intramuscular injection (IM)

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/50) x2
    Arm description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (50/150) x2
    Arm description
    Norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Arm title
    GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Arm description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 1 and Day 28.
    Arm type
    Experimental

    Investigational medicinal product name
    Norovirus Bivalent Virus-Like Particle (VLP) Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Norovirus GI.1/GII.4 bivalent VLP vaccine IM injection

    Number of subjects in period 1
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Started
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Completed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    27
    28
    29
    31
    Not completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
         Withdrawal by Subject
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -
         Protocol Violation
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GI.1/GII.4 (15/15) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, intramuscular (IM), on Day 1, followed by norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus virus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MLP) and 500 µg aluminum hydroxide, IM on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/15) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/150)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - Al(OH)3 (167)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group title
    GI.1/GII.4 (50/150) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2 Total
    Number of subjects
    30 30 30 31 30 31 30 32 29 30 29 28 29 31 420
    Age categorical
    Units: Subjects
        18-49 Years
    15 14 15 15 15 15 15 16 15 15 15 14 15 16 210
        50-64 Years
    15 16 15 16 15 16 15 16 14 15 14 14 14 15 210
    Age continuous
    Units: years
        median (full range (min-max))
    50 (19 to 63) 51 (20 to 64) 50 (22 to 64) 50 (20 to 64) 49.5 (20 to 64) 50 (20 to 64) 49.5 (18 to 64) 48.5 (18 to 63) 41 (21 to 63) 51 (20 to 63) 49 (21 to 62) 48.5 (23 to 64) 48 (22 to 63) 44 (19 to 64) -
    Gender categorical
    Units: Subjects
        Female
    18 20 20 22 19 23 15 18 20 23 16 16 20 18 268
        Male
    12 10 10 9 11 8 15 14 9 7 13 12 9 13 152
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    0 0 0 0 0 1 0 0 0 0 0 0 0 0 1
        Asian
    1 0 0 1 0 1 0 0 1 1 0 0 0 0 5
        White
    29 30 30 30 30 29 30 32 28 29 29 28 29 31 414
    Region of Enrollment
    Units: Subjects
        Belgium
    30 30 30 31 30 31 30 32 29 30 29 28 29 31 420
    Height
    Units: cm
        median (full range (min-max))
    173 (156 to 187) 167 (154 to 193) 166.5 (153 to 191) 167 (149 to 187) 171 (155 to 186) 169 (153 to 190) 173.5 (154 to 189) 169.5 (161 to 192) 171 (153 to 193) 167 (153 to 186) 172 (156 to 199) 171.5 (161 to 192) 170 (153 to 187) 175 (146 to 192) -
    Weight
    Units: kg
        median (full range (min-max))
    69.5 (49.4 to 105.2) 65.6 (49.1 to 103) 70.6 (50.8 to 104) 66.6 (42.2 to 103.3) 71.6 (47.6 to 101.9) 68.5 (44 to 96) 72.5 (45.8 to 104.5) 74.35 (52 to 110.3) 76 (54.8 to 101.2) 69.85 (50 to 92.6) 70 (49.6 to 94) 75.5 (42.5 to 92.5) 70.6 (49.2 to 111.8) 69.9 (51 to 111.3) -
    Body Mass ndex (BMI)
    Units: kg/m^2
        median (full range (min-max))
    25.22 (16.7 to 33.6) 23.97 (18.9 to 34.2) 26.11 (17.3 to 33.4) 23.62 (18.7 to 33.7) 24.51 (18.6 to 34.2) 24.73 (17.6 to 34.4) 24.4 (18.1 to 33.7) 24.06 (17.8 to 33.2) 26.06 (19 to 34.6) 25.02 (20 to 34.4) 23.66 (18.1 to 32.3) 24.24 (14.9 to 32.7) 23.19 (18.7 to 33.8) 24.54 (17.9 to 33.5) -

    End points

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    End points reporting groups
    Reporting group title
    GI.1/GII.4 (15/15) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, intramuscular (IM), on Day 1, followed by norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus virus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MLP) and 500 µg aluminum hydroxide, IM on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/15) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/150)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - Al(OH)3 (167)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group title
    GI.1/GII.4 (50/150) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Primary: Percentage of Participants With a Seroresponse (Pan-Ig ELISA)

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    End point title
    Percentage of Participants With a Seroresponse (Pan-Ig ELISA) [1]
    End point description
    Seroresponse was defined as 4-fold rise or greater 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). Full Analysis Set included all randomized participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Baseline and Day 56
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    31
    30
    31
    30
    32
    28
    30
    26
    28
    29
    30
    Units: percentage of participants
        number (confidence interval 95%)
    43.3 (25.5 to 62.6)
    62.1 (42.3 to 79.3)
    46.4 (27.5 to 66.1)
    35.5 (19.2 to 54.6)
    80 (61.4 to 92.3)
    67.7 (48.6 to 83.3)
    30 (14.7 to 49.4)
    62.5 (43.7 to 78.9)
    42.9 (24.5 to 62.8)
    66.7 (47.2 to 82.7)
    46.2 (26.6 to 66.6)
    71.4 (51.3 to 86.8)
    69 (49.2 to 84.7)
    56.7 (37.4 to 74.5)
    No statistical analyses for this end point

    Primary: Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After Dose 1

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    End point title
    Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After Dose 1 [2]
    End point description
    Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after each vaccination. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Days 1 through 7
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (not applicable)
        Pain
    43.3
    33.3
    50
    32.3
    46.7
    38.7
    40
    53.1
    44.8
    53.3
    48.3
    46.4
    31
    32.3
        Erythema
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Induration
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Swelling
    0
    0
    0
    0
    0
    0
    0
    0
    3.4
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After Dose 2

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    End point title
    Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After Dose 2 [3]
    End point description
    Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after each vaccination. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Days 28 through 34
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (not applicable)
        Pain
    60
    36.7
    66.7
    51.6
    53.3
    58.1
    33.3
    43.8
    48.3
    46.7
    34.5
    32.1
    41.4
    35.5
        Erythema
    0
    0
    3.3
    0
    0
    0
    0
    0
    3.4
    3.3
    0
    0
    0
    0
        Induration
    0
    0
    3.3
    0
    6.7
    0
    0
    0
    3.4
    3.3
    0
    0
    0
    0
        Swelling
    0
    3.3
    0
    3.2
    0
    3.2
    0
    0
    6.9
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Participants With Solicited Systemic Adverse Events (AEs) After Dose 1

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    End point title
    Percentage of Participants With Solicited Systemic Adverse Events (AEs) After Dose 1 [4]
    End point description
    Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after each vaccination. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Days 1 through 7
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (not applicable)
        Headache
    20
    26.7
    3.3
    19.4
    16.7
    12.9
    13.3
    25
    27.6
    20
    13.8
    17.9
    31
    19.4
        Fatigue
    23.3
    23.3
    16.7
    19.4
    10
    12.9
    13.3
    15.6
    17.2
    20
    24.1
    25
    17.2
    22.6
        Myalgia
    20
    6.7
    13.3
    6.5
    3.3
    9.7
    6.7
    18.8
    10.3
    10
    17.2
    10.7
    3.4
    19.4
        Arthralgia
    0
    3.3
    6.7
    0
    3.3
    0
    3.3
    6.3
    6.9
    3.3
    3.4
    3.6
    3.4
    3.2
        Vomitting
    0
    3.3
    0
    0
    0
    3.2
    0
    0
    0
    3.3
    3.4
    0
    0
    0
        Diarrhea
    0
    23.3
    3.3
    16.1
    20
    6.5
    13.3
    12.5
    13.8
    10
    6.9
    7.1
    10.3
    12.9
    No statistical analyses for this end point

    Primary: Percentage of Participants With Solicited Systemic Adverse Events (AEs) After Dose 2

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    End point title
    Percentage of Participants With Solicited Systemic Adverse Events (AEs) After Dose 2 [5]
    End point description
    Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after each vaccination. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Days 28 through 34
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (not applicable)
        Headache
    13.3
    13.3
    13.3
    22.6
    23.3
    16.1
    10
    21.9
    20.7
    10
    13.8
    14.3
    34.5
    19.4
        Fatigue
    16.7
    13.3
    20
    12.9
    10
    12.9
    10
    18.8
    17.2
    13.3
    13.8
    7.1
    13.8
    12.9
        Myalgia
    13.3
    3.3
    13.3
    0
    13.3
    12.9
    0
    6.3
    6.9
    0
    10.3
    7.1
    0
    6.5
        Arthralgia
    0
    3.3
    3.3
    0
    3.3
    3.2
    0
    3.1
    0
    3.3
    3.4
    3.6
    0
    3.2
        Vomiting
    0
    0
    0
    0
    0
    0
    0
    0
    0
    3.3
    3.4
    0
    0
    0
        Diarrhea
    3.3
    10
    16.7
    12.9
    16.7
    9.7
    6.7
    15.6
    17.2
    10
    3.4
    7.1
    6.9
    3.2
    No statistical analyses for this end point

    Primary: Oral Body Temperature Within 7 Days After Dose 1

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    End point title
    Oral Body Temperature Within 7 Days After Dose 1 [6]
    End point description
    Oral body temperature measurement is to be performed using the thermometer provided by the site for 7 days after each vaccination. The highest body temperature observed each day will be recorded on the Diary Card also provided by the site. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Days 1 through 7
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    30
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: degrees Celsius
        arithmetic mean (standard deviation)
    36.54 ± 0.294
    36.76 ± 0.376
    36.66 ± 0.345
    36.71 ± 0.26
    36.65 ± 0.388
    36.67 ± 0.255
    36.74 ± 0.323
    36.63 ± 0.366
    36.52 ± 0.405
    36.77 ± 0.341
    36.71 ± 0.404
    36.61 ± 0.368
    36.7 ± 0.362
    36.61 ± 0.381
    No statistical analyses for this end point

    Primary: Oral Body Temperature Within 7 Days After Dose 2

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    End point title
    Oral Body Temperature Within 7 Days After Dose 2 [7]
    End point description
    Oral body temperature measurement is to be performed using the thermometer provided by the site for 7 days after each vaccination. The highest body temperature observed each day will be recorded on the Diary Card also provided by the site. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Days 28 through 34
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    27
    28
    29
    31
    Units: degrees Celsius
        arithmetic mean (standard deviation)
    36.54 ± 0.282
    36.76 ± 0.301
    36.68 ± 0.351
    36.75 ± 0.466
    36.6 ± 0.286
    36.72 ± 0.317
    36.71 ± 0.394
    36.64 ± 0.342
    36.59 ± 0.463
    36.73 ± 0.293
    36.68 ± 0.345
    36.56 ± 0.351
    36.76 ± 0.391
    36.61 ± 0.386
    No statistical analyses for this end point

    Primary: Percentage of Participants With Unsolicited Adverse Events (AEs)

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    End point title
    Percentage of Participants With Unsolicited Adverse Events (AEs) [8]
    End point description
    Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study. Safety population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Day 1 up to Day 56
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
        number (not applicable)
    56.7
    60
    53.3
    45.2
    43.3
    54.8
    43.3
    62.5
    69
    43.3
    48.3
    50
    51.7
    61.3
    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) [9]
    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 population included all participants who received at least one dose of trial vaccine.
    End point type
    Primary
    End point timeframe
    Day 1 up to Day 393
    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: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
        number (not applicable)
    6.7
    0
    16.7
    6.5
    3.3
    0
    10
    9.4
    3.4
    3.3
    3.4
    7.1
    3.4
    3.2
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a Seroresponse on Day 28, Day 208 and Day 393 (Pan-Ig ELISA)

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    End point title
    Percentage of Participants With a Seroresponse on Day 28, Day 208 and Day 393 (Pan-Ig ELISA)
    End point description
    Seroresponse was defined as 4-fold rise or greater 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). D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    0 (0 to 11.6)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 10.9)
    0 (0 to 12.3)
    0 (0 to 11.6)
    0 (0 to 12.8)
    71.4 (51.3 to 86.8)
    79.3 (60.3 to 92)
    67.7 (48.6 to 83.3)
        D208 (n=30,29,30,31,30,30,30,32,29,30,27,28,29,28)
    10 (2.1 to 26.5)
    17.2 (5.8 to 35.8)
    10 (2.1 to 26.5)
    19.4 (7.5 to 37.5)
    20 (7.7 to 38.6)
    20 (7.7 to 38.6)
    6.7 (0.8 to 22.1)
    34.4 (18.6 to 53.2)
    17.2 (5.8 to 35.8)
    23.3 (9.9 to 42.3)
    14.8 (4.2 to 33.7)
    32.1 (15.9 to 52.4)
    34.5 (17.9 to 54.3)
    35.7 (18.6 to 55.9)
        D393 (n=29,29,30,31,30,29,29,32,29,30,27,28,29,29)
    17.2 (5.8 to 35.8)
    20.7 (8 to 39.7)
    13.3 (3.8 to 30.7)
    16.1 (5.5 to 33.7)
    10 (2.1 to 26.5)
    13.8 (3.9 to 31.7)
    10.3 (2.2 to 27.4)
    15.6 (5.3 to 32.8)
    6.9 (0.8 to 22.8)
    13.3 (3.8 to 30.7)
    7.4 (0.9 to 24.3)
    21.4 (8.3 to 41)
    20.7 (8 to 39.7)
    20.7 (8 to 39.7)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a 4-Fold Rise or Greater in GI.1 VLP Antibody Titer (Pan-Ig ELISA)

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in GI.1 VLP Antibody Titer (Pan-Ig ELISA)
    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 pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA). D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 12.8)
    6.9 (0.8 to 22.8)
    0 (0 to 11.6)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 10.9)
    0 (0 to 12.8)
    0 (0 to 11.6)
    4.2 (0.1 to 21.1)
    85.7 (67.3 to 96)
    93.1 (77.2 to 99.2)
    93.3 (77.9 to 99.2)
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    80 (61.4 to 92.3)
    89.7 (72.6 to 97.8)
    100 (87.7 to 100)
    89.7 (72.6 to 97.8)
    93.3 (77.9 to 99.2)
    96.8 (83.3 to 99.9)
    86.7 (69.3 to 96.2)
    87.5 (71 to 96.5)
    92.9 (76.5 to 99.1)
    90 (73.5 to 97.9)
    83.3 (62.6 to 95.3)
    85.7 (67.3 to 96)
    96.6 (82.2 to 99.9)
    86.7 (69.3 to 96.2)
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    60 (40.6 to 77.3)
    65.5 (45.7 to 82.1)
    67.9 (47.6 to 84.1)
    72.4 (52.8 to 87.3)
    70 (50.6 to 85.3)
    73.3 (54.1 to 87.7)
    66.7 (47.2 to 82.7)
    62.5 (43.7 to 78.9)
    85.7 (67.3 to 96)
    60 (40.6 to 77.3)
    54.2 (32.8 to 74.4)
    71.4 (51.3 to 86.8)
    75.9 (56.5 to 89.7)
    74.1 (53.7 to 88.9)
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    55.2 (35.7 to 73.6)
    46.4 (27.5 to 66.1)
    67.9 (47.6 to 84.1)
    69 (49.2 to 84.7)
    63.3 (43.9 to 80.1)
    65.5 (45.7 to 82.1)
    55.2 (35.7 to 73.6)
    53.1 (34.7 to 70.9)
    82.1 (63.1 to 93.9)
    43.3 (25.5 to 62.6)
    45.8 (25.6 to 67.2)
    64.3 (44.1 to 81.4)
    72.4 (52.8 to 87.3)
    78.6 (59 to 91.7)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With a 4-Fold Rise or Greater in GII.4 VLP Antibody Titer (Pan-Ig ELISA)

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in GII.4 VLP Antibody Titer (Pan-Ig ELISA)
    End point description
    The percentage of participants with a 4-fold rise or greater from 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). D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 12.8)
    0 (0 to 11.9)
    0 (0 to 11.6)
    0 (0 to 11.2)
    3.3 (0.1 to 17.2)
    3.1 (0.1 to 16.2)
    0 (0 to 12.8)
    3.3 (0.1 to 17.2)
    0 (0 to 14.2)
    78.6 (59 to 91.7)
    86.2 (68.3 to 96.1)
    70 (50.6 to 85.3)
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    50 (31.3 to 68.7)
    65.5 (45.7 to 82.1)
    46.4 (27.5 to 66.1)
    41.4 (23.5 to 61.1)
    83.3 (65.3 to 94.4)
    71 (52 to 85.8)
    33.3 (17.3 to 52.8)
    71.9 (53.3 to 86.3)
    42.9 (24.5 to 62.8)
    73.3 (54.1 to 87.7)
    54.2 (32.8 to 74.4)
    78.6 (59 to 91.7)
    72.4 (52.8 to 87.3)
    63.3 (43.9 to 80.1)
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    16.7 (5.6 to 34.7)
    27.6 (12.7 to 47.2)
    7.1 (0.9 to 23.5)
    27.6 (12.7 to 47.2)
    36.7 (19.9 to 56.1)
    23.3 (9.9 to 42.3)
    16.7 (5.6 to 34.7)
    46.9 (29.1 to 65.3)
    14.3 (4 to 32.7)
    30 (14.7 to 49.4)
    16.7 (4.7 to 37.4)
    35.7 (18.6 to 55.9)
    41.4 (23.5 to 61.1)
    33.3 (16.5 to 54)
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    20.7 (8 to 39.7)
    32.1 (15.9 to 52.4)
    10.7 (2.3 to 28.2)
    27.6 (12.7 to 47.2)
    20 (7.7 to 38.6)
    17.2 (5.8 to 35.8)
    17.2 (5.8 to 35.8)
    21.9 (9.3 to 40)
    10.7 (2.3 to 28.2)
    13.3 (3.8 to 30.7)
    8.3 (1 to 27)
    28.6 (13.2 to 48.7)
    27.6 (12.7 to 47.2)
    21.4 (8.3 to 41)
    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. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,30,30,31,30,31,30,32,29,30,29,28,29,31)
    833.4 ± 4.64
    790.3 ± 4.5
    636.7 ± 4.6
    647.6 ± 5.17
    625.3 ± 2.96
    520.3 ± 4.99
    890.5 ± 4.75
    842.9 ± 4.92
    677.2 ± 3.75
    827.3 ± 4.82
    856.7 ± 5.34
    741.5 ± 5.28
    897.5 ± 3.74
    742.7 ± 3.69
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    798.9 ± 4.66
    737.9 ± 4.42
    548.5 ± 4.47
    806.6 ± 5.36
    573.6 ± 3.08
    514.6 ± 5.19
    910.4 ± 4.37
    821.5 ± 4.84
    638.5 ± 3.9
    780.6 ± 5.11
    889.7 ± 5.34
    14488.6 ± 3
    20839.2 ± 1.96
    15967.7 ± 2.39
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    14417.7 ± 2.74
    14171.3 ± 2.76
    17504.8 ± 2.64
    14220.4 ± 3.23
    13982.2 ± 2.33
    18266 ± 1.99
    16082.5 ± 2.07
    15974.2 ± 3.95
    25808.9 ± 2.55
    154663 ± 2.59
    14045.2 ± 2.94
    12613.2 ± 2.46
    17696.3 ± 1.92
    12235.7 ± 2.11
        D208 (n=30,29,30,31,30,30,30,32,29,30,27,28,29,29)
    5725.2 ± 2.37
    5069.7 ± 2.48
    6084.3 ± 2.43
    5613.9 ± 2.68
    4467.6 ± 2.05
    5106.4 ± 2.06
    5660.5 ± 2.22
    7174.8 ± 2.47
    7542 ± 2.28
    5361.1 ± 2.37
    5162.8 ± 2.18
    6863.9 ± 2.27
    7459.1 ± 1.72
    5912.6 ± 1.94
        D393 (n=29,29,30,31,30,29,29,32,29,30,27,28,29,29)
    3886 ± 2.98
    3179.7 ± 2.78
    4470.4 ± 2.55
    5009 ± 2.8
    3209.6 ± 2.54
    3874.5 ± 2.55
    4940.3 ± 2.48
    4773.3 ± 2.62
    5550.1 ± 2.7
    3542.9 ± 2.54
    3960 ± 2.55
    4715.8 ± 2.51
    5686.7 ± 2.17
    4404.7 ± 2.19
    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. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,30,30,31,30,31,30,32,29,30,29,28,29,31)
    1106.6 ± 4.68
    1249.2 ± 3.45
    1477.7 ± 4.13
    1109.2 ± 4.1
    921.7 ± 3.15
    1130.9 ± 4.18
    1340.4 ± 4.08
    1238.6 ± 3.92
    1201.2 ± 3.57
    1473.2 ± 3.88
    1832.3 ± 2.69
    977.7 ± 3.73
    1324.4 ± 3.34
    1647 ± 3.39
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    1016.8 ± 5.56
    1232.6 ± 3.46
    1540.6 ± 3.83
    1110.4 ± 3.84
    839.4 ± 3.04
    1097.8 ± 4.14
    1268.1 ± 3.68
    1311 ± 3.98
    1139.9 ± 3.48
    1494.7 ± 3.05
    1924.8 ± 2.52
    8459.4 ± 2.19
    12901.7 ± 2.12
    11116.3 ± 2.55
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    4595.7 ± 3
    8636.7 ± 2.05
    5750.4 ± 2.15
    4391.5 ± 2.66
    7545.2 ± 2.61
    7802.7 ± 2.03
    3444.6 ± 2.92
    9945.7 ± 2.98
    5129.9 ± 2.91
    10624.2 ± 2.15
    10034.2 ± 1.96
    6622 ± 2.22
    9995.5 ± 2.13
    8164 ± 2.32
        D208 (n=30,29,30,31,30,30,30,32,29,30,27,28,29,29)
    2341.2 ± 3.93
    3653 ± 2.24
    2993.2 ± 3.61
    2887.7 ± 2.78
    2984.6 ± 2.62
    3212.2 ± 2.44
    2251.1 ± 3.15
    5017.6 ± 2.82
    2615.1 ± 2.91
    4531.4 ± 2.21
    4667 ± 2.2
    3837.9 ± 2.3
    4693.8 ± 2.52
    4546.8 ± 2.26
        D393 (n=29,29,30,31,30,29,29,32,29,30,27,28,29,29)
    2236.5 ± 3.84
    3103 ± 3.03
    2450.2 ± 2.87
    2175.3 ± 2.91
    1946.4 ± 2.51
    2173.7 ± 2.73
    2267.2 ± 3.29
    2969.9 ± 2.92
    1898.2 ± 3.41
    2550 ± 2.29
    2871.1 ± 2.43
    2425.1 ± 2.46
    3133 ± 2.5
    3060.7 ± 2.44
    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. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: ratio
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    1 ± 1.13
    0.9 ± 1.18
    0.8 ± 1.5
    1.2 ± 2.85
    0.9 ± 1.26
    1 ± 1.16
    1 ± 1.36
    1 ± 1.18
    0.9 ± 1.28
    0.9 ± 1.28
    1 ± 1.58
    19.5 ± 3.73
    23.2 ± 3
    22 ± 2.57
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    17.3 ± 3.69
    18.8 ± 3.46
    25.8 ± 3.09
    22.4 ± 4.38
    22.4 ± 3.02
    35.1 ± 3.88
    18.1 ± 4.35
    19 ± 3.67
    36.5 ± 4.85
    18.7 ± 3.31
    13.5 ± 3.07
    17 ± 3.63
    19.7 ± 2.78
    16.8 ± 2.74
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    6.9 ± 3.63
    6.7 ± 3.71
    9.3 ± 3.77
    9 ± 4.32
    7.1 ± 2.63
    10.4 ± 3.79
    6.4 ± 3.62
    8.5 ± 3.9
    10.7 ± 3
    6.5 ± 2.96
    5.2 ± 3.27
    9.3 ± 3.57
    8.3 ± 2.79
    78 ± 3.52
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    4.4 ± 3.27
    4.1 ± 4.46
    7 ± 3.56
    8 ± 4.65
    5.1 ± 2.41
    7.4 ± 3.36
    5.3 ± 3.4
    5.7 ± 3.41
    7.8 ± 2.87
    4.3 ± 2.58
    4 ± 3.08
    6.4 ± 4.07
    6.3 ± 2.95
    6.1 ± 2.85
    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. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: ratio
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0.9 ± 1.56
    1 ± 1.14
    1 ± 1.23
    1 ± 1.21
    0.9 ± 1.18
    1 ± 1.13
    0.9 ± 1.37
    1.1 ± 1.57
    1 ± 1.17
    1 ± 1.58
    1 ± 1.25
    8.7 ± 3.25
    9.7 ± 3.02
    6.7 ± 3.11
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    4.2 ± 3.11
    7.2 ± 2.98
    4 ± 2.66
    4.1 ± 2.97
    8.2 ± 2.72
    6.9 ± 3.31
    2.6 ± 2.6
    8 ± 3.36
    4 ± 3
    7.2 ± 3.38
    4.7 ± 1.97
    6.8 ± 2.99
    7.5 ± 2.74
    5 ± 2.7
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    2.1 ± 2.45
    3 ± 2.74
    1.9 ± 1.96
    2.6 ± 2.5
    3.2 ± 2.36
    2.7 ± 2.21
    1.7 ± 2.17
    4.1 ± 2.45
    2 ± 2.06
    3.1 ± 2.61
    2.2 ± 1.92
    3.9 ± 2.7
    3.5 ± 2.24
    2.5 ± 2.57
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    1.9 ± 2.77
    2.6 ± 3.2
    1.7 ± 2.41
    2 ± 2.33
    2.1 ± 2.34
    1.9 ± 1.99
    1.6 ± 2.46
    2.4 ± 2.4
    1.5 ± 2.27
    1.7 ± 2.41
    1.4 ± 2.27
    2.5 ± 2.6
    2.4 ± 2.22
    1.7 ± 2.64
    No statistical analyses for this end point

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

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP and GII.4 VLP Antibody Titers (IgA ELISA)
    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 immunoglobulin A (IgA) enzyme-linked immunosorbent assay (ELISA) for all arms on day 28 and day 56. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    0 (0 to 11.6)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 11.2)
    3.03 (0.1 to 17.2)
    0 (0 to 10.9)
    0 (0 to 12.3)
    0 (0 to 11.6)
    0 (0 to 12.8)
    71.4 (51.3 to 86.8)
    72.4 (52.8 to 87.3)
    64.5 (45.4 to 80.8)
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    53.3 (34.3 to 71.7)
    58.6 (38.9 to 76.5)
    39.3 (21.5 to 59.4)
    45.2 (27.3 to 64)
    70 (50.6 to 85.3)
    58.1 (39.1 to 75.5)
    36.7 (19.9 to 56.1)
    65.6 (46.8 to 81.4)
    42.9 (24.5 to 62.8)
    66.7 (47.2 to 82.7)
    50 (29.9 to 70.1)
    57.1 (37.2 to 75.5)
    51.7 (32.5 to 70.6)
    46.7 (28.3 to 65.7)
    No statistical analyses for this end point

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

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP and GII.4 VLP Antibody Titers (IgA ELISA) [10]
    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 immunoglobulin A (IgA) enzyme-linked immunosorbent assay (ELISA) for selected arms on day 208 and day 393. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 208 and 393
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: percentage of participants
    number (confidence interval 95%)
        D208 (n=30,32)
    30 (14.7 to 49.4)
    25 (11.5 to 43.4)
        D393 (n=30,31)
    13.3 (3.8 to 30.7)
    6.5 (0.8 to 21.4)
    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 (IgA ELISA)

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (IgA ELISA)
    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 immunoglobulin A (IgA) enzyme-linked immunosorbent assay (ELISA) for all arms on day 28 and day 56. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 12.8)
    6.9 (0.8 to 22.8)
    0 (0 to 11.6)
    0 (0 to 11.2)
    3.3 (0.1 to 17.2)
    0 (0 to 10.9)
    0 (0 to 12.8)
    0 (0 to 11.6)
    4.2 (0.1 to 21.1)
    96.4 (81.7 to 99.9)
    100 (88.1 to 100)
    100 (88.4 to 100)
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    93.3 (77.9 to 99.2)
    89.7 (72.6 to 97.8)
    100 (87.7 to 100)
    89.7 (72.6 to 97.8)
    96.7 (82.8 to 99.9)
    100 (88.8 to 100)
    90 (73.5 to 97.9)
    90.6 (75 to 98)
    96.4 (81.7 to 99.9)
    100 (88.4 to 100)
    87.5 (67.6 to 97.3)
    96.4 (81.7 to 99.9)
    100 (88.1 to 100)
    100 (88.4 to 100)
    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 (IgA ELISA)

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (IgA ELISA) [11]
    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 immunoglobulin A (IgA) enzyme-linked immunosorbent assay (ELISA) for selected arms on day 208 and day 393. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 208 and 393
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: percentage of participants
    number (confidence interval 95%)
        D208 (n=30,32)
    80 (61.4 to 92.3)
    71.9 (53.3 to 86.3)
        D393 (n=30,31)
    73.3 (54.1 to 87.7)
    54.8 (36 to 72.7)
    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 (IgA ELISA)

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (IgA ELISA)
    End point description
    The percentage of participants with a 4-fold rise from or greater in serum anti-norovirus antibody titers for GII.4 virus-like particle (VLP) as measured by immunoglobulin A (IgA) enzyme-linked immunosorbent assay (ELISA) for all arms on day 28 and day 56. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 12.8)
    0 (0 to 11.7)
    0 (0 to 11.9)
    0 (0 to 11.2)
    3.3 (0.1 to 17.2)
    3.1 (0.1 to 16.2)
    0 (0 to 12.8)
    3.3 (0.1 to 17.2)
    0 (0 to 14.2)
    75 (55.1 to 89.3)
    72.4 (52.8 to 87.3)
    63.3 (43.9 to 80.1)
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,
    53.3 (34.3 to 71.7)
    65.5 (45.7 to 82.1)
    39.3 (21.5 to 59.4)
    51.7 (32.5 to 70.6)
    73.3 (54.1 to 87.7)
    58.1 (39.1 to 75.5)
    36.7 (19.9 to 56.1)
    68.8 (50 to 83.9)
    46.4 (27.5 to 66.1)
    66.7 (47.2 to 82.7)
    54.2 (32.8 to 74.4)
    60.7 (40.6 to 78.5)
    51.7 (32.5 to 70.6)
    46.7 (28.3 to 65.7)
    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 (IgA ELISA)

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    End point title
    Percentage of Participants With a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (IgA ELISA) [12]
    End point description
    The percentage of participants with a 4-fold rise from or greater in serum anti-norovirus antibody titers for GII.4 virus-like particle (VLP) as measured by immunoglobulin A (IgA) enzyme-linked immunosorbent assay (ELISA) for selected arms on day 208 and day 393. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 208 and 393
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: percentage of participants
    number (confidence interval 95%)
        D208 (n=30,32)
    36.7 (19.9 to 56.1)
    34.4 (18.6 to 53.2)
        D393 (n=30,31)
    23.3 (9.9 to 42.3)
    16.1 (5.5 to 33.7)
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (IgA ELISA)
    End point description
    Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by IgA ELISA for all arms on day 28 and day 56. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,30,30,31,30,31,30,32,29,30,29,28,29,31)
    52.9 ± 4.86
    37.4 ± 3.59
    42.1 ± 3.63
    32.1 ± 5.26
    30.1 ± 3.26
    44.5 ± 6.06
    53.6 ± 5.76
    60.1 ± 6.45
    36.8 ± 5.3
    58.5 ± 4.08
    47 ± 4.91
    73.3 ± 5.24
    40.8 ± 4.25
    41.5 ± 3.74
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    48.9 ± 4.99
    34.6 ± 3.38
    41.2 ± 3.85
    41 ± 4.38
    29.4 ± 3.31
    46.2 ± 6.22
    54.4 ± 5.67
    59.8 ± 6.23
    37.8 ± 5.2
    56.3 ± 3.95
    57 ± 5.31
    1649.9 ± 4.88
    2148.2 ± 2.98
    1703.2 ± 2.62
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    1358.4 ± 4.02
    996.2 ± 5.02
    2223.3 ± 2.91
    1068.7 ± 5.39
    1368.6 ± 3.99
    1849.8 ± 3.35
    1594.9 ± 4.87
    1435.5 ± 7.02
    2074.3 ± 4.4
    1510.6 ± 4.45
    1131.2 ± 4.28
    810.7 ± 5.58
    922.6 ± 3.73
    848.2 ± 3.63
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (IgA ELISA) [13]
    End point description
    Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by IgA ELISA for selected arms on day 208 and day 393. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 208 and 393
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        D208 (n=30,32)
    302.5 ± 4.1
    512.4 ± 5.85
        D393 (n=30,31)
    224 ± 2.73
    340.1 ± 3.91
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (IgA ELISA)
    End point description
    Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by IgA ELISA for all arms on day 28 and day 56. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,30,30,31,30,31,30,32,29,30,29,28,29,31)
    83.4 ± 6.63
    113.6 ± 4.43
    145.5 ± 4.72
    119.5 ± 4.47
    72.8 ± 4.64
    114.6 ± 4.56
    100.2 ± 4.47
    133 ± 4.77
    114.3 ± 4.65
    158.5 ± 3.41
    201.7 ± 3.3
    105.9 ± 4.08
    121.9 ± 4.16
    174.5 ± 4.13
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    77.8 ± 6.49
    110 ± 4.31
    151.2 ± 4.7
    125.3 ± 4.34
    73.8 ± 4.42
    116.3 ± 4.49
    106.3 ± 4.05
    139.2 ± 5.48
    106.3 ± 4.71
    164.8 ± 3.16
    218.8 ± 3.07
    953.5 ± 2.83
    948.2 ± 2.52
    1118 ± 2.91
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    495.7 ± 3.3
    840.8 ± 2.87
    583.7 ± 2.34
    467.9 ± 2.79
    803.3 ± 3.24
    714.2 ± 2.44
    336.7 ± 3.74
    1088.9 ± 3.72
    513.9 ± 3.82
    1117.7 ± 3.03
    1027.3 ± 2.36
    578.8 ± 3.11
    552.2 ± 2.6
    691.2 ± 3.12
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (IgA ELISA) [14]
    End point description
    Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by IgA ELISA for selected arms on day 208 and day 393. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        D208 (n=30,32)
    251.8 ± 3.94
    427.9 ± 3.95
        D393 (n=30,31)
    139.7 ± 4.07
    273.4 ± 3.59
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (IgA ELISA)
    End point description
    Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by IgA ELISA for all arms on day 28 and day 56. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: ratio
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0.9 ± 1.52
    0.9 ± 1.49
    1 ± 1.23
    1.3 ± 2.65
    1 ± 1.23
    1 ± 1.14
    1 ± 1.44
    1 ± 1.1
    1 ± 1.13
    1 ± 1.46
    1.2 ± 1.86
    22.5 ± 2.95
    52.7 ± 2.79
    42.3 ± 2.39
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    25.7 ± 4.46
    28 ± 4.4
    49.2 ± 2.81
    34.2 ± 5.55
    45.4 ± 3.47
    41.5 ± 3.5
    29.8 ± 4.63
    23.9 ± 4.13
    52.1 ± 3.61
    25.8 ± 3.15
    20.8 ± 2.77
    11.1 ± 2.19
    22.6 ± 2.29
    21.1 ± 2.81
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (IgA ELISA) [15]
    End point description
    Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by IgA ELISA for selected arms on day 208 and day 393. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: ratio
    geometric mean (standard deviation)
        D208 (n=30,32)
    10 ± 2.89
    8.5 ± 3.77
        D393 (n=30,31)
    7.4 ± 2.41
    5.2 ± 3.34
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (IgA ELISA)
    End point description
    Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by IgA ELISA for all arms on day 28 and day 56. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: ratio
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0.9 ± 1.33
    1 ± 1.42
    1 ± 1.13
    1.1 ± 1.27
    1 ± 1.14
    1 ± 1.09
    1.1 ± 1.44
    1 ± 1.6
    1 ± 1.1
    1 ± 1.36
    1 ± 1.22
    9 ± 2.85
    7.8 ± 2.89
    6.3 ± 3.11
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    5.9 ± 4.37
    7.7 ± 3.92
    3.6 ± 2.45
    4.2 ± 2.54
    11 ± 3.48
    6.2 ± 3.36
    3.4 ± 2.7
    8.2 ± 3.36
    4 ± 3.14
    7.1 ± 2.81
    4.9 ± 2.35
    5.5 ± 4.74
    4.5 ± 2.53
    3.9 ± 2.41
    No statistical analyses for this end point

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

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    End point title
    Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (IgA ELISA) [16]
    End point description
    Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by IgA ELISA for selected arms on day 208 and day 393. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: ratio
    geometric mean (standard deviation)
        D208 (n=30,32)
    3.5 ± 2.67
    3.2 ± 2.44
        D393 (n=30,31)
    1.9 ± 2.47
    1.9 ± 2.26
    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. D=Day Full Analysis Set included all randomized participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    0 (0 to 11.6)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 10.9)
    0 (0 to 12.3)
    0 (0 to 11.6)
    0 (0 to 12.8)
    67.9 (47.6 to 84.1)
    62.1 (42.3 to 79.3)
    67.7 (48.6 to 83.3)
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    33.3 (17.3 to 52.8)
    55.2 (35.7 to 73.6)
    32.1 (15.9 to 52.4)
    35.5 (19.2 to 54.6)
    66.7 (47.2 to 82.7)
    51.6 (33.1 to 69.8)
    26.7 (12.3 to 45.9)
    59.4 (40.6 to 76.3)
    28.6 (13.2 to 48.7)
    60 (40.6 to 77.3)
    53.8 (33.4 to 73.4)
    75 (55.1 to 89.3)
    58.6 (38.9 to 76.5)
    56.7 (37.4 to 74.5)
        D208 (n=30,29,30,31,30,30,30,32,29,30,27,28,29,28)
    10 (2.1 to 26.5)
    20.7 (8 to 39.7)
    16.7 (5.6 to 34.7)
    6.5 (0.8 to 21.4)
    13.3 (3.8 to 30.7)
    13.3 (3.8 to 30.7)
    20 (7.7 to 38.6)
    31.3 (16.1 to 50)
    20.7 (8 to 39.7)
    16.7 (5.6 to 34.7)
    7.4 (0.9 to 24.3)
    42.9 (24.5 to 62.8)
    34.5 (17.9 to 54.3)
    21.4 (8.3 to 41)
        D393 (n=29,29,30,31,30,29,29,32,29,30,27,28,29,28)
    3.4 (0.1 to 17.8)
    13.8 (3.9 to 31.7)
    6.7 (0.8 to 22.1)
    3.2 (0.1 to 16.7)
    6.7 (0.8 to 22.1)
    3.4 (0.1 to 17.8)
    6.9 (0.8 to 22.8)
    9.4 (2 to 25)
    3.4 (0.1 to 17.8)
    3.3 (0.1 to 17.2)
    3.7 (0.1 to 19)
    7.1 (0.9 to 23.5)
    10.3 (2.2 to 27.4)
    7.1 (0.9 to 23.5)
    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. D=Day Per-Protocol Set included all participants who received both doses of study drug and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0 (0 to 11.6)
    0 (0 to 11.9)
    0 (0 to 12.8)
    0 (0 to 11.9)
    0 (0 to 11.6)
    0 (0 to 11.2)
    0 (0 to 11.6)
    0 (0 to 10.9)
    0 (0 to 12.8)
    0 (0 to 11.6)
    0 (0 to 14.2)
    82.1 (63.1 to 93.9)
    96.6 (82.2 to 99.9)
    93.3 (77.9 to 99.2)
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    80 (61.4 to 92.3)
    79.3 (60.3 to 92)
    85.7 (67.3 to 96)
    82.8 (64.2 to 94.2)
    86.7 (69.3 to 96.2)
    87.1 (70.2 to 96.4)
    76.7 (57.7 to 90.1)
    78.1 (60 to 90.7)
    85.7 (67.3 to 96)
    90 (73.5 to 97.9)
    70.8 (48.9 to 87.4)
    100 (87.7 to 100)
    96.6 (82.2 to 99.9)
    93.3 (77.9 to 99.2)
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    53.3 (34.3 to 71.7)
    65.5 (45.7 to 82.1)
    67.9 (47.6 to 84.1)
    58.6 (38.9 to 76.5)
    43.3 (25.5 to 62.6)
    70 (50.6 to 85.3)
    60 (40.6 to 77.3)
    78.1 (60 to 90.7)
    82.1 (63.1 to 93.9)
    56.7 (37.4 to 74.5)
    33.3 (15.6 to 55.3)
    85.7 (67.3 to 96)
    93.1 (77.2 to 99.2)
    77.8 (57.7 to 91.4)
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    31 (15.3 to 50.8)
    32.1 (15.9 to 52.4)
    50 (30.6 to 69.4)
    37.9 (20.7 to 57.7)
    23.3 (9.9 to 42.3)
    37.9 (20.7 to 57.7)
    44.8 (26.4 to 64.3)
    53.1 (34.7 to 70.9)
    53.6 (33.9 to 72.5)
    26.7 (12.3 to 45.9)
    29.2 (12.6 to 51.1)
    50 (30.6 to 69.4)
    51.7 (32.5 to 70.6)
    46.4 (27.5 to 66.1)
    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. D=Day Per-Protocol Set included all participants who received both doses of study drug and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: percentage of participants
    number (confidence interval 95%)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    3.3 (0.1 to 17.2)
    0 (0 to 11.9)
    3.7 (0.1 to 19)
    0 (0 to 11.9)
    3.3 (0.1 to 17.2)
    0 (0 to 11.2)
    0 (0 to 11.6)
    3.1 (0.1 to 16.2)
    3.7 (0.1 to 19)
    3.3 (0.1 to 17.2)
    0 (0 to 14.2)
    82.1 (63.1 to 93.9)
    65.5 (45.7 to 82.1)
    70 (50.6 to 85.3)
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    46.7 (28.3 to 65.7)
    72.4 (52.8 to 87.3)
    39.3 (21.5 to 59.4)
    41.4 (23.5 to 61.1)
    80 (61.4 to 92.3)
    61.3 (42.2 to 78.2)
    26.7 (12.3 to 45.9)
    71.9 (53.3 to 86.3)
    35.7 (18.6 to 55.9)
    63.3 (43.9 to 80.1)
    66.7 (44.7 to 84.4)
    75 (55.1 to 89.3)
    58.6 (38.9 to 76.5)
    60 (40.6 to 77.3)
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    26.7 (12.3 to 45.9)
    31 (15.3 to 50.8)
    17.9 (6.1 to 36.9)
    20.7 (8 to 39.7)
    43.3 (25.5 to 62.6)
    20 (7.7 to 38.6)
    20 (7.7 to 38.6)
    43.8 (26.4 to 62.3)
    21.4 (8.3 to 41)
    33.3 (17.3 to 52.8)
    25 (9.8 to 46.7)
    50 (30.6 to 69.4)
    37.9 (20.7 to 57.7)
    22.2 (8.6 to 42.3)
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    13.8 (3.9 to 31.7)
    21.4 (8.3 to 41)
    3.6 (0.1 to 18.3)
    17.2 (5.8 to 35.8)
    23.3 (9.9 to 42.3)
    3.4 (0.1 to 17.8)
    10.3 (2.2 to 27.4)
    12.5 (3.5 to 29)
    10.7 (2.3 to 28.2)
    16.7 (5.6 to 34.7)
    4.2 (0.1 to 21.1)
    21.4 (8.3 to 41)
    24.1 (10.3 to 43.5)
    10.7 (2.3 to 28.2)
    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. D=Day Full Analysis Set included all participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,30,30,31,30,31,30,32,29,30,29,28,29,31)
    24.8 ± 2.75
    18.7 ± 1.85
    26 ± 2.73
    26.8 ± 3.35
    19.1 ± 1.68
    24.8 ± 2.31
    30.5 ± 3.04
    24.5 ± 2.59
    23.8 ± 2.46
    23.2 ± 2.19
    26.3 ± 2.68
    23.1 ± 2.25
    22.3 ± 2.26
    20.6 ± 2.04
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    25 ± 2.6
    18.6 ± 1.86
    23.8 ± 2.44
    26.7 ± 3.19
    18.6 ± 1.7
    23 ± 2.24
    27.3 ± 2.46
    25.1 ± 2.52
    25.5 ± 2.52
    24.8 ± 2.37
    28.5 ± 2.66
    347.6 ± 4.62
    385.9 ± 3.64
    391.1 ± 3.56
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    280.5 ± 3.94
    236.3 ± 4.61
    403.3 ± 3.74
    286.9 ± 5.01
    22.86 ± 3.94
    356.4 ± 3.74
    400.1 ± 3.33
    412.9 ± 4.78
    510 ± 4.36
    247.2 ± 3.43
    271.3 ± 5
    398.6 ± 2.7
    463.5 ± 2.32
    355.8 ± 2.58
        D208 (n=30,29,30,31,30,30,30,32,29,30,27,28,29,29)
    130 ± 3.38
    98.2 ± 3.46
    159 ± 3.23
    136.4 ± 3.67
    80.1 ± 3.49
    139.3 ± 2.68
    159.8 ± 2.73
    202.1 ± 3.34
    208.6 ± 3.28
    114.5 ± 2.89
    107.9 ± 3.28
    196.4 ± 2.86
    219.2 ± 2.29
    182 ± 2.4
        D393 (n=29,29,30,31,30,29,29,32,29,30,27,28,29,29)
    67.8 ± 3.78
    51.3 ± 3.23
    88.1 ± 6.54
    74.8 ± 4.26
    44 ± 3.39
    71.9 ± 3.4
    91.5 ± 3.14
    107.5 ± 3.97
    99.6 ± 4.09
    55 ± 3.22
    66.1 ± 3.86
    103.4 ± 3.95
    113.6 ± 3.3
    81 ± 2.85
    No statistical analyses for this end point

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

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    End point title
    Blocking Titers 50 (BT50) of 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. D=Day Full Analysis Set included all participants who received at least one dose of trial vaccine. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,30,30,31,30,31,30,32,29,30,29,28,29,31)
    66 ± 4.85
    80.1 ± 3.44
    115.3 ± 4.24
    91.4 ± 4.15
    60.9 ± 3.84
    96.6 ± 4.03
    80.7 ± 4.48
    89.8 ± 4.41
    96.2 ± 3.93
    102.3 ± 3.39
    121.9 ± 3.47
    56.1 ± 3.48
    92 ± 3.96
    117.8 ± 3.91
        D28 (n=30,30,29,31,30,31,30,32,28,30,27,28,29,31)
    69.3 ± 4.56
    75.7 ± 3.63
    124.9 ± 3.98
    87.9 ± 3.75
    67.7 ± 3.76
    94.5 ± 4.3
    74.6 ± 4.17
    98.1 ± 5.11
    92.9 ± 3.87
    123.3 ± 3.25
    117.6 ± 3.62
    552.6 ± 3.65
    688.4 ± 3.16
    904.4 ± 2.67
        D56 (n=30,29,28,31,30,31,30,32,28,30,26,28,29,30)
    336.9 ± 3.4
    686.3 ± 3.47
    429 ± 2.4
    317.8 ± 2.94
    675.7 ± 3.21
    632.1 ± 2.11
    189.2 ± 4.63
    842.8 ± 3.23
    360.1 ± 3.85
    862.8 ± 3.12
    778 ± 2.57
    426.5 ± 3.46
    596.3 ± 2.86
    604.4 ± 2.91
        D208 (n=30,29,30,31,30,30,30,32,29,30,27,28,29,29)
    186.7 ± 3.19
    241.5 ± 3.24
    244.6 ± 2.78
    206.3 ± 2.84
    229.9 ± 3.6
    259.7 ± 2.66
    142.5 ± 4.09
    346.8 ± 2.92
    201 ± 3.49
    340.6 ± 2.6
    324.6 ± 3.07
    277.5 ± 2.53
    350.9 ± 2.36
    295.3 ± 3.07
        D393 (n=29,29,30,31,30,29,29,32,29,30,27,28,29,28)
    120.5 ± 4.21
    180.2 ± 3.95
    123.5 ± 3.87
    133.2 ± 3.81
    104.7 ± 4.01
    134.4 ± 3.74
    109.3 ± 4.44
    182.9 ± 3.6
    121.9 ± 3.88
    179.7 ± 2.53
    209 ± 3.38
    126.2 ± 3.56
    171.2 ± 3.61
    192.9 ± 3.52
    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
    Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28, 56, 208 and 393
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: titer
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    1 ± 1.3
    1 ± 1.08
    0.9 ± 1.3
    1 ± 1.21
    1 ± 1.37
    0.9 ± 1.26
    0.9 ± 1.59
    1 ± 1.22
    1.1 ± 1.37
    1.1 ± 1.28
    1 ± 1.31
    15 ± 3.8
    17.3 ± 3.02
    19.3 ± 3.33
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    11.3 ± 4.25
    13.2 ± 4.31
    14.9 ± 3.54
    10 ± 4.07
    12 ± 3.36
    14.3 ± 2.98
    13.1 ± 3.96
    16.9 ± 4.6
    21.1 ± 3.72
    10.7 ± 2.53
    9.7 ± 4.29
    17.2 ± 2.36
    20.8 ± 2.2
    17.9 ± 2.68
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    5.2 ± 3.41
    5.5 ± 3.18
    6 ± 2.97
    4.8 ± 2.91
    4.2 ± 2.94
    5.9 ± 2
    5.2 ± 2.69
    8.2 ± 3.14
    8.6 ± 2.63
    4.9 ± 2.24
    3.7 ± 2.95
    8.5 ± 2.52
    9.8 ± 2.18
    7.9 ± 2.21
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    2.7 ± 3.29
    2.7 ± 2.71
    3.3 ± 2.87
    2.6 ± 2.97
    2.3 ± 2.65
    3 ± 2.35
    2.9 ± 2.61
    4.4 ± 3.3
    4 ± 3.1
    2.4 ± 2.35
    2.4 ± 2.73
    4.5 ± 3.29
    5.1 ± 2.81
    3.8 ± 2.6
    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
    Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by the HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: titer
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    1.1 ± 1.68
    0.9 ± 1.59
    1 ± 1.47
    1 ± 1.73
    1.1 ± 1.62
    1 ± 1.38
    0.9 ± 1.29
    1.1 ± 1.89
    1 ± 1.59
    1.2 ± 2.45
    1 ± 1.46
    9.8 ± 3.48
    7.5 ± 3.13
    7 ± 2.96
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    5.1 ± 4.42
    8.9 ± 3.31
    3.6 ± 2.71
    3.7 ± 3.43
    11.1 ± 3.32
    6.5 ± 3.33
    2.3 ± 2.95
    9.4 ± 3.95
    3.5 ± 3.61
    8.4 ± 3.59
    6 ± 2.24
    7.6 ± 3.19
    6.5 ± 2.94
    4.8 ± 2.46
        D208 (n=30,29,28,29,30,30,30,32,28,30,24,28,29,27)
    2.8 ± 3.1
    3.1 ± 2.51
    2 ± 2.42
    2.4 ± 2.58
    3.8 ± 2.56
    2.5 ± 1.99
    1.8 ± 2.27
    3.9 ± 3.03
    2 ± 2.3
    3.3 ± 2.66
    2.5 ± 1.73
    4.9 ± 2.72
    3.8 ± 2.81
    2.5 ± 2.35
        D393 (n=29,28,28,29,30,29,29,32,28,30,24,28,29,28)
    1.7 ± 3.14
    2.3 ± 2.42
    1 ± 2.43
    1.5 ± 2.56
    1.7 ± 2.32
    1.4 ± 1.82
    1.3 ± 2.25
    2 ± 2.59
    1.3 ± 2.28
    1.8 ± 2.11
    1.6 ± 1.9
    2.2 ± 2.7
    1.9 ± 2.62
    1.4 ± 2.23
    No statistical analyses for this end point

    Secondary: GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA)

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    End point title
    GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA)
    End point description
    GMFR of anti-norovirus GII.4 Cincinnati antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: titer
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    1 ± 1.17
    1 ± 1.18
    0.9 ± 1.12
    1 ± 1.22
    1 ± 1.11
    0.9 ± 1.22
    0.9 ± 1.18
    1 ± 1.67
    0.9 ± 1.98
    1 ± 1.12
    1 ± 1.13
    7.4 ± 2.97
    4.5 ± 2.94
    5.7 ± 3.01
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    3.4 ± 2.91
    5.1 ± 2.78
    1.7 ± 1.81
    2.6 ± 2.78
    4.2 ± 3.2
    3.7 ± 3.17
    1.6 ± 2.06
    5.9 ± 4.17
    2.7 ± 3.16
    4.6 ± 2.73
    3.1 ± 2.36
    4.6 ± 2.94
    3.6 ± 2.62
    4 ± 2.45
    No statistical analyses for this end point

    Secondary: GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA)

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    End point title
    GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA) [17]
    End point description
    GMFR of anti-norovirus GII.4 Cincinnati antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        D208 (n=30,32)
    1.8 ± 2.34
    2.4 ± 2.89
        D393 (n=30,32)
    1.4 ± 2.08
    1.9 ± 2.56
    No statistical analyses for this end point

    Secondary: GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA)

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    End point title
    GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA)
    End point description
    GMFR of anti-norovirus GII.4 Sydney antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: titer
    geometric mean (standard deviation)
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    0.9 ± 1.22
    1 ± 1.26
    0.9 ± 1.12
    1 ± 1.18
    0.9 ± 1.22
    1 ± 1.09
    0.9 ± 1.47
    1.1 ± 1.91
    1 ± 1.05
    1 ± 1.25
    1 ± 1.06
    2.2 ± 2.48
    2.5 ± 2.8
    2.8 ± 2.77
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    1.5 ± 2.59
    2.3 ± 2.1
    1.3 ± 1.67
    1.3 ± 1.48
    2 ± 2.46
    1.7 ± 1.82
    1.1 ± 1.6
    2.9 ± 3.5
    1.6 ± 1.77
    2.5 ± 2.62
    2 ± 2.02
    1.8 ± 2.25
    1.9 ± 2.3
    2.1 ± 2.25
    No statistical analyses for this end point

    Secondary: GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA)

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    End point title
    GMFR of Antibody Titers of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA) [18]
    End point description
    GMFR of anti-norovirus GII.4 Sydney antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        D208 (n=30,32)
    1.4 ± 1.93
    1.6 ± 2.1
        D393 (n=30,32)
    1 ± 1.78
    1.4 ± 2.28
    No statistical analyses for this end point

    Secondary: GMFR of Antibody Titers of Strains Not Represented in the Investigational Vaccine: Cross-Protection Assays

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    End point title
    GMFR of Antibody Titers of Strains Not Represented in the Investigational Vaccine: Cross-Protection Assays [19]
    End point description
    GMFR of anti-norovirus Cross-Protection Assays: GII.2 EC50, GI.3 EC50 and GII.4.2012 EC50 antibody titers as measured by HBGA binding assay. Data was collected for selected arms only. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. Data was only collected for 2 of the arms.
    End point type
    Secondary
    End point timeframe
    Day 56
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        GII.2 EC50
    1.1 ± 1.92
    0.8 ± 3.73
        GI.3 EC50
    5.9 ± 3.23
    3 ± 3.36
        GII.4.2012 EC50
    3.2 ± 2.5
    4.1 ± 3.51
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA)
    End point description
    Blocking titers 50 (BT50) of anti-norovirus GII.4 Cincinnati antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    63.7 ± 4.34
    75.1 ± 3.85
    114.7 ± 4.28
    85.8 ± 4.19
    63 ± 4.08
    89.1 ± 4.13
    99.8 ± 4.47
    85 ± 4.64
    91.8 ± 4.02
    112.6 ± 3.26
    134.8 ± 3.07
    54 ± 3.95
    81.8 ± 3.86
    93.2 ± 3.75
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    63.6 ± 4.31
    72.9 ± 3.95
    113.8 ± 4.02
    83.3 ± 4.05
    61.7 ± 4.04
    84.4 ± 4.23
    90.5 ± 4.16
    88 ± 5.49
    78.6 ± 4.06
    109 ± 3.25
    130.6 ± 2.95
    400 ± 3.57
    366.9 ± 4.6
    534.2 ± 3.17
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    217.3 ± 3.57
    380.7 ± 3.61
    200.3 ± 4.33
    221 ± 3.66
    263.7 ± 5.77
    327.5 ± 4.12
    161.5 ± 4.66
    501.4 ± 5.07
    248.5 ± 4.56
    518.8 ± 3.4
    415.5 ± 4.11
    248.3 ± 4.01
    296.5 ± 4.12
    373.4 ± 3.4
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Cincinnati (HBGA) [20]
    End point description
    Blocking titers 50 (BT50) of anti-norovirus GII.4 Cincinnati antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        D208 (n=30,32)
    113.5 ± 5.03
    202.5 ± 4.06
        D393 (n=30,32)
    88.9 ± 3.9
    160.8 ± 3.96
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA)
    End point description
    Blocking Titers 50 (BT50) of anti-norovirus GII.4 Sydney antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Days 28 and 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    29
    28
    29
    30
    31
    30
    32
    28
    30
    24
    28
    29
    30
    Units: titer
    geometric mean (standard deviation)
        D1 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    35 ± 3.86
    26 ± 2.3
    43.3 ± 3.29
    32.4 ± 3.24
    28.3 ± 2.45
    37.5 ± 3.18
    29.7 ± 3.34
    28 ± 2.93
    32.2 ± 3.09
    28.1 ± 2.31
    32.3 ± 2.79
    21.6 ± 2.11
    29.7 ± 2.48
    37.3 ± 3.42
        D28 (n=30,29,27,29,30,31,30,32,27,30,24,28,29,30)
    32.6 ± 3.49
    24.8 ± 2.29
    42.5 ± 3.1
    31.1 ± 3.12
    26.4 ± 2.44
    36.3 ± 3.09
    25.9 ± 3.08
    30.2 ± 3.87
    32.9 ± 3.09
    27.8 ± 2.28
    31.8 ± 2.73
    48 ± 3.37
    75.1 ± 3.35
    104.8 ± 3.35
        D56 (n=30,29,28,29,30,31,30,32,28,30,24,28,29,30)
    53.5 ± 3.93
    59.3 ± 2.79
    56.7 ± 3.06
    40.6 ± 3.37
    55.5 ± 3.33
    62.1 ± 3.26
    31.2 ± 3.04
    80.6 ± 4.37
    51.2 ± 3.31
    70.4 ± 3.22
    64.4 ± 3.52
    38.8 ± 2.98
    56.7 ± 3.15
    79.1 ± 3.18
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: GII.4 Sydney (HBGA) [21]
    End point description
    Blocking Titers 50 (BT50) of anti-norovirus GII.4 Sydney antibody titers as measured by HBGA binding assay. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. “n” in the category is the number of participants with data available at the given time-point.
    End point type
    Secondary
    End point timeframe
    Days 208 and 393
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        D208 (n=30,32)
    40.2 ± 3.14
    44.2 ± 3.17
        D393 (n=30,32)
    28.5 ± 2.37
    38.3 ± 2.87
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: Cross-Protection Assay: GII.2 EC50 (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: Cross-Protection Assay: GII.2 EC50 (HBGA) [22]
    End point description
    Blocking titers 50 (BT50) of anti-norovirus Cross-Protection Assay: GII.2 EC50 antibody titers as measured by HBGA binding assay. Data was collected for selected arms only. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. Data was only collected for 2 of the arms.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 56
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        Day 1
    266.2 ± 2.62
    265.5 ± 4.79
        Day 56
    295.8 ± 2.31
    216.5 ± 4.46
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: Cross-Protection Assay: GI.3 EC50 (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: Cross-Protection Assay: GI.3 EC50 (HBGA) [23]
    End point description
    Blocking titers 50 (BT50) of anti-norovirus Cross-Protection Assay: GI.3 EC50 antibody titers as measured by HBGA binding assay. Data was collected for selected arms only. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. Data was only collected for 2 of the arms.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 56
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        Day 1
    59.7 ± 2.98
    74.1 ± 3.7
        Day 56
    350.5 ± 3.05
    222.7 ± 5.09
    No statistical analyses for this end point

    Secondary: Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: Cross-Protection Assay: GII.4.2012 EC50 (HBGA)

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    End point title
    Blocking Titers 50 (BT50) of a Strain Not Represented in the Investigational Vaccine: Cross-Protection Assay: GII.4.2012 EC50 (HBGA) [24]
    End point description
    Blocking titers 50 (BT50) of anti-norovirus Cross-Protection Assay: GII.4.2012 EC50 antibody titers as measured by HBGA binding assay. Data was collected for selected arms only. D=Day Per-Protocol Set included all participants who received both doses of trial vaccine and who had no major protocol violations. Data was only collected for 2 of the arms.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) and Day 56
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis is reported for this endpoint.
    End point values
    GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (15/50)
    Number of subjects analysed
    30
    32
    Units: titer
    geometric mean (standard deviation)
        Day 1
    45.5 ± 4.07
    50.7 ± 5.1
        Day 56
    146.6 ± 3.11
    208.5 ± 3.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Significant New Medical Conditions

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    End point title
    Percentage of Participants With Significant New Medical Conditions
    End point description
    Significant new medical conditions will be evaluated by the investigator for the co-existence of any of the following conditions: Adverse events of special interest (AESIs) are predefined events for potential immune mediated disorders. All AESIs are medically evaluated to assess if they might indicate an immune-mediated disorder. Immune mediated events (IMEs) are AEs that represent a new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. Safety Analysis Set included all participants who received at least one dose of trial vaccine.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
    number (not applicable)
        AESIs
    6.7
    3.3
    0
    6.5
    0
    0
    6.7
    6.3
    0
    0
    0
    7.1
    3.4
    0
        IMEs
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    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 participants is unwilling to continue because of the AE. Safety Analysis Set included all participants who received at least one dose of trial vaccine.
    End point type
    Secondary
    End point timeframe
    Day 1 up to Day 56
    End point values
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Number of subjects analysed
    30
    30
    30
    31
    30
    31
    30
    32
    29
    30
    29
    28
    29
    31
    Units: percentage of participants
        number (not applicable)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Unsolicited AEs 28 days after each vaccination (Day 1 to 56) and Serious Adverse Events (SAEs) throughout the trial (Up to Day 393)
    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 used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    GI.1/GII.4 (15/15) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, intramuscular (IM), on Day 1, followed by norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus virus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MLP) and 500 µg aluminum hydroxide, IM on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50) - MPL (50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/15) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50) - MPL (15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 15 µg MLP and 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/15)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/50)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (50/150)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - Al(OH)3 (167)
    Reporting group description
    Hepatitis A vaccine, IM, on Day 1, followed by norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group title
    GI.1/GII.4 (50/150) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 150 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Reporting group title
    GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Reporting group description
    Norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 167 µg aluminum hydroxide, IM, on Day 1 and Day 28.

    Serious adverse events
    GI.1/GII.4 (15/15) - MPL (50) GI.1/GII.4 (15/50) - MPL (50) GI.1/GII.4 (50/50) - MPL (50) GI.1/GII.4 (15/15) - MPL (15) GI.1/GII.4 (15/50) - MPL (15) GI.1/GII.4 (50/50) - MPL (15) GI.1/GII.4 (15/15) GI.1/GII.4 (15/50) GI.1/GII.4 (50/50) GI.1/GII.4 (50/150) GI.1/GII.4 (15/50) - Al(OH)3 (167) GI.1/GII.4 (15/50) x2 GI.1/GII.4 (50/150) x2 GI.1/GII.4 (15/50) - Al(OH)3 (167) x2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 30 (6.67%)
    0 / 30 (0.00%)
    5 / 30 (16.67%)
    2 / 31 (6.45%)
    1 / 30 (3.33%)
    0 / 31 (0.00%)
    3 / 30 (10.00%)
    3 / 32 (9.38%)
    1 / 29 (3.45%)
    1 / 30 (3.33%)
    1 / 29 (3.45%)
    2 / 28 (7.14%)
    1 / 29 (3.45%)
    1 / 31 (3.23%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Compression fracture
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (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
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon injury
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cervix carcinoma
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (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
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    1 / 28 (3.57%)
    0 / 29 (0.00%)
    0 / 31 (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 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (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
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    1 / 30 (3.33%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Major depression
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    1 / 28 (3.57%)
    0 / 29 (0.00%)
    0 / 31 (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 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    1 / 31 (3.23%)
         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 / 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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
    0 / 29 (0.00%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (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
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal polyp
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 31 (0.00%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
    1 / 29 (3.45%)
    0 / 30 (0.00%)
    0 / 29 (0.00%)
    0 / 28 (0.00%)
    0 / 29 (0.00%)
    0 / 31 (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
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 30 (0.00%)
    0 / 30 (0.00%)</