Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2, Randomized, Controlled, Observer-Blinded Study to Describe the Immunogenicity, Safety, and Tolerability of Neisseria Meningitidis Serogroup B (MnB) Bivalent Recombinant Lipoprotein 2086 Vaccine (Bivalent rLP2086) in Healthy Subjects Aged Greater Than or Equal to (>=) 24 Months to Less Than (<) 10 Years

    Summary
    EudraCT number
    		 2014-000933-21
    Trial protocol
    		 FI  
    Global end of trial date
    01 Mar 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Sep 2017
    First version publication date
    14 Sep 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    B1971017 (6108K2-3012)
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02531698
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001037-PIP02-11
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Jun 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Mar 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Mar 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 4 primary MnB test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the third vaccination with bivalent rLP2086, in healthy subjects aged >=24 months to <4 years and >=4 years to <10 years at study entry and to evaluate the safety profile of bivalent rLP2086 compared to a control (hepatitis A virus [HAV] vaccine), as measured by local reactions, systemic events, adverse event (AEs), Serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), medically attended AEs (MAEs), and immediate AEs in healthy subjects aged >=24 months to <4 years and >=4 years to <10 years at study entry, and in both age strata combined.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Aug 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Finland: 156
    Country: Number of subjects enrolled
    Poland: 244
    Worldwide total number of subjects
    400
    EEA total number of subjects
    400
    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)
    400
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Four hundred subjects were enrolled at 14 centers, 6 in Finland and 8 in Poland. The study was conducted from 27 August 2015 to 1 March 2017.

    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
    		 Investigator, Subject, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years)
    Arm description
    		 Subjects from >=24 months to <4 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered 0.5 milliliter (mL) bivalent rLP2086 as intramuscular injection at Months 0, 2, and 6.

    Arm title
    		 Group 1 bivalent rLP2086 (>=4 years to <10 years)
    Arm description
    		 Subjects from >=4 years to <10 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered 0.5 mL bivalent rLP2086 as intramuscular injection at Months 0, 2, and 6.

    Arm title
    		 Group 2 HAV/Saline (>=24 months to <4 years)
    Arm description
    		 Subjects from >=24 months to <4 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    HAV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered 0.5 mL HAV vaccine as intramuscular injection at Months 0 and 6.

    Investigational medicinal product name
    Saline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered 0.5 mL saline solution as intramuscular injection at Month 2.

    Arm title
    		 Group 2 HAV/Saline (>=4 years to <10 years)
    Arm description
    		 Subjects from >=4 years to <10 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    HAV
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered 0.5 mL HAV vaccine as intramuscular injection at Months 0 and 6.

    Investigational medicinal product name
    Saline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects were administered 0.5 mL saline solution as intramuscular injection at Month 2.

    Number of subjects in period 1
    		Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years)
    Started
    145
    149
    55
    51
    Completed
    137
    146
    54
    50
    Not completed
    8
    3
    1
    1
         Consent withdrawn by subject
    4
    2
    1
    -
         Adverse event
    2
    -
    -
    1
         Lost to follow-up
    1
    -
    -
    -
         Protocol deviation
    1
    1
    -
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Group 1 bivalent rLP2086 (>=24 months to <4 years)
    Reporting group description
    		 Subjects from >=24 months to <4 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 1 bivalent rLP2086 (>=4 years to <10 years)
    Reporting group description
    		 Subjects from >=4 years to <10 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 2 HAV/Saline (>=24 months to <4 years)
    Reporting group description
    		 Subjects from >=24 months to <4 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Reporting group title
    Group 2 HAV/Saline (>=4 years to <10 years)
    Reporting group description
    		 Subjects from >=4 years to <10 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Reporting group values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Total
    Number of subjects
    		 145 149 55 51 400
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 145 149 55 51 400
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0 0
        From 65-84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 2.4 ( 0.5 ) 6.1 ( 1.72 ) 2.5 ( 0.5 ) 6 ( 1.64 ) -
    Gender, Male/Female
    Units: Subjects
        Female
    		 69 77 35 27 208
        Male
    		 76 72 20 24 192
    Subject analysis sets

    Subject analysis set title
    Group 1 bivalent rLP2086 (>=24 months to <10 years)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects from >=24 months to <10 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 2 HAV/Saline (>=24 months to <10 years)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects from >=24 months to <10 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Subject analysis sets values
    		 Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects
    294
    106
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    4.3 ( 2.24 )
    4.2 ( 2.15 )
    Gender, Male/Female
    Units: Subjects
        Female
    146
    62
        Male
    148
    44

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Group 1 bivalent rLP2086 (>=24 months to <4 years)
    Reporting group description
    		 Subjects from >=24 months to <4 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 1 bivalent rLP2086 (>=4 years to <10 years)
    Reporting group description
    		 Subjects from >=4 years to <10 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 2 HAV/Saline (>=24 months to <4 years)
    Reporting group description
    		 Subjects from >=24 months to <4 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Reporting group title
    Group 2 HAV/Saline (>=4 years to <10 years)
    Reporting group description
    		 Subjects from >=4 years to <10 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Subject analysis set title
    Group 1 bivalent rLP2086 (>=24 months to <10 years)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects from >=24 months to <10 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 2 HAV/Saline (>=24 months to <10 years)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects from >=24 months to <10 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Primary: Percentage of Subjects With hSBA Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With hSBA Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 3 [1]
    End point description
    Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95 percent (%) confidence interval (CIs). LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). Evaluable immunogenicity population included all eligible subjects randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, "n" signifies number of subjects evaluable for the specified test strain.
    End point type
    Primary
    End point timeframe
    1 month after Vaccination 3
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years)
    Number of subjects analysed
    136
    138
    52
    45
    Units: Percentage of subjects
    number (confidence interval 95%)
        PMB80 [A22] (n = 68, 67, 25, 20)
    83.8 (72.9 to 91.6)
    91 (81.5 to 96.6)
    4 (0.1 to 20.4)
    10 (1.2 to 31.7)
        PMB2001 [A56] (n = 68, 71, 24, 19)
    100 (94.7 to 100)
    100 (94.9 to 100)
    4.2 (0.1 to 21.1)
    42.1 (20.3 to 66.5)
        PMB2948 [B24] (n = 63, 63, 26, 20)
    85.7 (74.6 to 93.3)
    92.1 (82.4 to 97.4)
    7.7 (0.9 to 25.1)
    0 (0 to 16.8)
        PMB2707 [B44] (n = 65, 69, 26, 24)
    80 (68.2 to 88.9)
    78.3 (66.7 to 87.3)
    0 (0 to 13.2)
    0 (0 to 14.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 1 [2]
    End point description
    Local reactions included pain at injection site, swelling and redness collected by using an electronic diary (e-diary). Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity) and severe (prevented daily activity). Redness and swelling were graded as: mild (0.5-2.0 centimeter [cm]), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 7 Days after Vaccination 1
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
    number (confidence interval 95%)
        Pain at injection site: Any
    51.7 (43.3 to 60.1)
    79.9 (72.5 to 86)
    10.9 (4.1 to 22.2)
    35.3 (22.4 to 49.9)
    66 (60.3 to 71.4)
    22.6 (15.1 to 31.8)
        Pain at injection site: Mild
    24.1 (17.4 to 31.9)
    40.3 (32.3 to 48.6)
    9.1 (3 to 20)
    27.5 (15.9 to 41.7)
    32.3 (27 to 38)
    17.9 (11.2 to 26.6)
        Pain at injection site: Moderate
    24.8 (18 to 32.7)
    35.6 (27.9 to 43.8)
    1.8 (0 to 9.7)
    7.8 (2.2 to 18.9)
    30.3 (25.1 to 35.9)
    4.7 (1.5 to 10.7)
        Pain at injection site: Severe
    2.8 (0.8 to 6.9)
    4 (1.5 to 8.6)
    0 (0 to 6.5)
    0 (0 to 7)
    3.4 (1.6 to 6.2)
    0 (0 to 3.4)
        Redness: Any
    42.1 (33.9 to 50.5)
    39.6 (31.7 to 47.9)
    10.9 (4.1 to 22.2)
    7.8 (2.2 to 18.9)
    40.8 (35.1 to 46.7)
    9.4 (4.6 to 16.7)
        Redness: Mild
    22.1 (15.6 to 29.7)
    13.4 (8.4 to 20)
    7.3 (2 to 17.6)
    3.9 (0.5 to 13.5)
    17.7 (13.5 to 22.5)
    5.7 (2.1 to 11.9)
        Redness: Moderate
    18.6 (12.6 to 25.9)
    18.8 (12.9 to 26)
    3.6 (0.4 to 12.5)
    3.9 (0.5 to 13.5)
    18.7 (14.4 to 23.6)
    3.8 (1 to 9.4)
        Redness: Severe
    1.4 (0.2 to 4.9)
    7.4 (3.7 to 12.8)
    0 (0 to 6.5)
    0 (0 to 7)
    4.4 (2.4 to 7.4)
    0 (0 to 3.4)
        Swelling: Any
    27.6 (20.5 to 35.6)
    34.9 (27.3 to 43.1)
    5.5 (1.1 to 15.1)
    5.9 (1.2 to 16.2)
    31.3 (26 to 36.9)
    5.7 (2.1 to 11.9)
        Swelling: Mild
    11 (6.4 to 17.3)
    13.4 (8.4 to 20)
    3.6 (0.4 to 12.5)
    3.9 (0.5 to 13.5)
    12.2 (8.7 to 16.5)
    3.8 (1 to 9.4)
        Swelling: Moderate
    16.6 (10.9 to 23.6)
    18.1 (12.3 to 25.3)
    1.8 (0 to 9.7)
    2 (0 to 10.4)
    17.3 (13.2 to 22.2)
    1.9 (0.2 to 6.6)
        Swelling: Severe
    0 (0 to 2.5)
    3.4 (1.1 to 7.7)
    0 (0 to 6.5)
    0 (0 to 7)
    1.7 (0.6 to 3.9)
    0 (0 to 3.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 2 [3]
    End point description
    Local reactions included pain at injection site, swelling and redness collected by using an e-diary. Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity) and severe (prevented daily activity). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit. Here "number of subjects analyzed (N)" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 Days after Vaccination 2
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    143
    148
    54
    49
    291
    103
    Units: Percentage of subjects
    number (confidence interval 95%)
        Pain at injection site: Any
    63.6 (55.2 to 71.5)
    77.7 (70.1 to 84.1)
    5.6 (1.2 to 15.4)
    20.4 (10.2 to 34.3)
    70.8 (65.2 to 76)
    12.6 (6.9 to 20.6)
        Pain at injection site: Mild
    40.6 (32.4 to 49.1)
    39.9 (31.9 to 48.2)
    5.6 (1.2 to 15.4)
    14.3 (5.9 to 27.2)
    40.2 (34.5 to 46.1)
    9.7 (4.8 to 17.1)
        Pain at injection site: Moderate
    20.3 (14 to 27.8)
    36.5 (28.7 to 44.8)
    0 (0 to 6.6)
    6.1 (1.3 to 16.9)
    28.5 (23.4 to 34.1)
    2.9 (0.6 to 8.3)
        Pain at injection site: Severe
    2.8 (0.8 to 7)
    1.4 (0.2 to 4.8)
    0 (0 to 6.6)
    0 (0 to 7.3)
    2.1 (0.8 to 4.4)
    0 (0 to 3.5)
        Redness: Any
    36.4 (28.5 to 44.8)
    37.8 (30 to 46.2)
    5.6 (1.2 to 15.4)
    6.1 (1.3 to 16.9)
    37.1 (31.5 to 42.9)
    5.8 (2.2 to 12.2)
        Redness: Mild
    15.4 (9.9 to 22.4)
    17.6 (11.8 to 24.7)
    5.6 (1.2 to 15.4)
    6.1 (1.3 to 16.9)
    16.5 (12.4 to 21.3)
    5.8 (2.2 to 12.2)
        Redness: Moderate
    20.3 (14 to 27.8)
    16.2 (10.7 to 23.2)
    0 (0 to 6.6)
    0 (0 to 7.3)
    18.2 (14 to 23.1)
    0 (0 to 3.5)
        Redness: Severe
    0.7 (0 to 3.8)
    4.1 (1.5 to 8.6)
    0 (0 to 6.6)
    0 (0 to 7.3)
    2.4 (1 to 4.9)
    0 (0 to 3.5)
        Swelling: Any
    27.3 (20.2 to 35.3)
    29.7 (22.5 to 37.8)
    0 (0 to 6.6)
    2 (0.1 to 10.9)
    28.5 (23.4 to 34.1)
    1 (0 to 5.3)
        Swelling: Mild
    11.9 (7.1 to 18.4)
    11.5 (6.8 to 17.8)
    0 (0 to 6.6)
    2 (0.1 to 10.9)
    11.7 (8.2 to 15.9)
    1 (0 to 5.3)
        Swelling: Moderate
    14.7 (9.3 to 21.6)
    17.6 (11.8 to 24.7)
    0 (0 to 6.6)
    0 (0 to 7.3)
    16.2 (12.1 to 20.9)
    0 (0 to 3.5)
        Swelling: Severe
    0.7 (0 to 3.8)
    0.7 (0 to 3.7)
    0 (0 to 6.6)
    0 (0 to 7.3)
    0.7 (0.1 to 2.5)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 3 [4]
    End point description
    Local reactions included pain at injection site, swelling and redness collected by using an e-diary. Pain was graded as: mild (did not interfere with activity), moderate (interfered with activity) and severe (prevented daily activity). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 Days after Vaccination 3
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    139
    146
    54
    50
    285
    104
    Units: Percentage of subjects
    number (confidence interval 95%)
        Pain at injection site: Any
    54.7 (46 to 63.1)
    81.5 (74.2 to 87.4)
    9.3 (3.1 to 20.3)
    22 (11.5 to 36)
    68.4 (62.7 to 73.8)
    15.4 (9.1 to 23.8)
        Pain at injection site: Mild
    26.6 (19.5 to 34.8)
    49.3 (41 to 57.7)
    7.4 (2.1 to 17.9)
    14 (5.8 to 26.7)
    38.2 (32.6 to 44.2)
    10.6 (5.4 to 18.1)
        Pain at injection site: Moderate
    25.2 (18.2 to 33.2)
    28.8 (21.6 to 36.8)
    1.9 (0 to 9.9)
    8 (2.2 to 19.2)
    27 (21.9 to 32.6)
    4.8 (1.6 to 10.9)
        Pain at injection site: Severe
    2.9 (0.8 to 7.2)
    3.4 (1.1 to 7.8)
    0 (0 to 6.6)
    0 (0 to 7.1)
    3.2 (1.5 to 5.9)
    0 (0 to 3.5)
        Redness: Any
    34.5 (26.7 to 43.1)
    35.6 (27.9 to 44)
    9.3 (3.1 to 20.3)
    10 (3.3 to 21.8)
    35.1 (29.6 to 40.9)
    9.6 (4.7 to 17)
        Redness: Mild
    15.8 (10.2 to 23)
    17.1 (11.4 to 24.2)
    7.4 (2.1 to 17.9)
    10 (3.3 to 21.8)
    16.5 (12.4 to 21.3)
    8.7 (4 to 15.8)
        Redness: Moderate
    17.3 (11.4 to 24.6)
    12.3 (7.5 to 18.8)
    1.9 (0 to 9.9)
    0 (0 to 7.1)
    14.7 (10.8 to 19.4)
    1 (0 to 5.2)
        Redness: Severe
    1.4 (0.2 to 5.1)
    6.2 (2.9 to 11.4)
    0 (0 to 6.6)
    0 (0 to 7.1)
    3.9 (1.9 to 6.8)
    0 (0 to 3.5)
        Swelling: Any
    24.5 (17.6 to 32.5)
    30.1 (22.8 to 38.3)
    3.7 (0.5 to 12.7)
    6 (1.3 to 16.5)
    27.4 (22.3 to 32.9)
    4.8 (1.6 to 10.9)
        Swelling: Mild
    9.4 (5.1 to 15.5)
    14.4 (9.1 to 21.1)
    1.9 (0 to 9.9)
    6 (1.3 to 16.5)
    11.9 (8.4 to 16.3)
    3.8 (1.1 to 9.6)
        Swelling: Moderate
    15.1 (9.6 to 22.2)
    14.4 (9.1 to 21.1)
    1.9 (0 to 9.9)
    0 (0 to 7.1)
    14.7 (10.8 to 19.4)
    1 (0 to 5.2)
        Swelling: Severe
    0 (0 to 2.6)
    1.4 (0.2 to 4.9)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.7 (0.1 to 2.5)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 1 [5]
    End point description
    Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, >39.5 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily activity). Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 7 Days after Vaccination 1
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever >=38 degrees Celsius (C)
    21.4 (15 to 29)
    11.4 (6.8 to 17.6)
    10.9 (4.1 to 22.2)
    2 (0 to 10.4)
    16.3 (12.3 to 21.1)
    6.6 (2.7 to 13.1)
        Fever 38 to <38.5 degrees C
    6.9 (3.4 to 12.3)
    5.4 (2.3 to 10.3)
    7.3 (2 to 17.6)
    2 (0 to 10.4)
    6.1 (3.7 to 9.5)
    4.7 (1.5 to 10.7)
        Fever 38.5 to <39 degrees C
    7.6 (3.8 to 13.2)
    4.7 (1.9 to 9.4)
    3.6 (0.4 to 12.5)
    0 (0 to 7)
    6.1 (3.7 to 9.5)
    1.9 (0.2 to 6.6)
        Fever 39 to <39.5 degrees C
    3.4 (1.1 to 7.9)
    1.3 (0.2 to 4.8)
    0 (0 to 6.5)
    0 (0 to 7)
    2.4 (1 to 4.8)
    0 (0 to 3.4)
        Fever 39.5 to 40 degrees C
    2.8 (0.8 to 6.9)
    0 (0 to 2.4)
    0 (0 to 6.5)
    0 (0 to 7)
    1.4 (0.4 to 3.4)
    0 (0 to 3.4)
        Fever >40 degrees C
    0.7 (0 to 3.8)
    0 (0 to 2.4)
    0 (0 to 6.5)
    0 (0 to 7)
    0.3 (0 to 1.9)
    0 (0 to 3.4)
        Vomiting: Any
    9 (4.9 to 14.8)
    2 (0.4 to 5.8)
    5.5 (1.1 to 15.1)
    2 (0 to 10.4)
    5.4 (3.1 to 8.7)
    3.8 (1 to 9.4)
        Vomiting: Mild
    7.6 (3.8 to 13.2)
    1.3 (0.2 to 4.8)
    5.5 (1.1 to 15.1)
    0 (0 to 7)
    4.4 (2.4 to 7.4)
    2.8 (0.6 to 8)
        Vomiting: Moderate
    1.4 (0.2 to 4.9)
    0.7 (0 to 3.7)
    0 (0 to 6.5)
    2 (0 to 10.4)
    1 (0.2 to 3)
    0.9 (0 to 5.1)
        Vomiting: Severe
    0 (0 to 2.5)
    0 (0 to 2.4)
    0 (0 to 6.5)
    0 (0 to 7)
    0 (0 to 1.2)
    0 (0 to 3.4)
        Diarrhea: Any
    11.7 (7 to 18.1)
    6.7 (3.3 to 12)
    7.3 (2 to 17.6)
    5.9 (1.2 to 16.2)
    9.2 (6.1 to 13.1)
    6.6 (2.7 to 13.1)
        Diarrhea: Mild
    9 (4.9 to 14.8)
    5.4 (2.3 to 10.3)
    7.3 (2 to 17.6)
    5.9 (1.2 to 16.2)
    7.1 (4.5 to 10.7)
    6.6 (2.7 to 13.1)
        Diarrhea: Moderate
    2.1 (0.4 to 5.9)
    1.3 (0.2 to 4.8)
    0 (0 to 6.5)
    0 (0 to 7)
    1.7 (0.6 to 3.9)
    0 (0 to 3.4)
        Diarrhea: Severe
    0.7 (0 to 3.8)
    0 (0 to 2.4)
    0 (0 to 6.5)
    0 (0 to 7)
    0.3 (0 to 1.9)
    0 (0 to 3.4)
        Headache: Any
    8.3 (4.3 to 14)
    28.2 (21.1 to 36.1)
    3.6 (0.4 to 12.5)
    19.6 (9.8 to 33.1)
    18.4 (14.1 to 23.3)
    11.3 (6 to 18.9)
        Headache: Mild
    3.4 (1.1 to 7.9)
    15.4 (10 to 22.3)
    1.8 (0 to 9.7)
    11.8 (4.4 to 23.9)
    9.5 (6.4 to 13.5)
    6.6 (2.7 to 13.1)
        Headache: Moderate
    4.8 (2 to 9.7)
    12.1 (7.3 to 18.4)
    1.8 (0 to 9.7)
    5.9 (1.2 to 16.2)
    8.5 (5.6 to 12.3)
    3.8 (1 to 9.4)
        Headache: Severe
    0 (0 to 2.5)
    0.7 (0 to 3.7)
    0 (0 to 6.5)
    2 (0 to 10.4)
    0.3 (0 to 1.9)
    0.9 (0 to 5.1)
        Fatigue: Any
    55.9 (47.4 to 64.1)
    42.3 (34.2 to 50.6)
    20 (10.4 to 33)
    31.4 (19.1 to 45.9)
    49 (43.1 to 54.8)
    25.5 (17.5 to 34.9)
        Fatigue: Mild
    24.1 (17.4 to 31.9)
    19.5 (13.4 to 26.7)
    9.1 (3 to 20)
    19.6 (9.8 to 33.1)
    21.8 (17.2 to 26.9)
    14.2 (8.1 to 22.3)
        Fatigue: Moderate
    27.6 (20.5 to 35.6)
    19.5 (13.4 to 26.7)
    5.5 (1.1 to 15.1)
    11.8 (4.4 to 23.9)
    23.5 (18.7 to 28.7)
    8.5 (4 to 15.5)
        Fatigue: Severe
    4.1 (1.5 to 8.8)
    3.4 (1.1 to 7.7)
    5.5 (1.1 to 15.1)
    0 (0 to 7)
    3.7 (1.9 to 6.6)
    2.8 (0.6 to 8)
        Muscle pain : Any
    13.1 (8.1 to 19.7)
    19.5 (13.4 to 26.7)
    1.8 (0 to 9.7)
    9.8 (3.3 to 21.4)
    16.3 (12.3 to 21.1)
    5.7 (2.1 to 11.9)
        Muscle pain : Mild
    6.2 (2.9 to 11.5)
    11.4 (6.8 to 17.6)
    1.8 (0 to 9.7)
    7.8 (2.2 to 18.9)
    8.8 (5.9 to 12.7)
    4.7 (1.5 to 10.7)
        Muscle pain : Moderate
    4.8 (2 to 9.7)
    7.4 (3.7 to 12.8)
    0 (0 to 6.5)
    2 (0 to 10.4)
    6.1 (3.7 to 9.5)
    0.9 (0 to 5.1)
        Muscle pain : Severe
    2.1 (0.4 to 5.9)
    0.7 (0 to 3.7)
    0 (0 to 6.5)
    0 (0 to 7)
    1.4 (0.4 to 3.4)
    0 (0 to 3.4)
        Joint pain: Any
    6.2 (2.9 to 11.5)
    6.7 (3.3 to 12)
    1.8 (0 to 9.7)
    7.8 (2.2 to 18.9)
    6.5 (3.9 to 9.9)
    4.7 (1.5 to 10.7)
        Joint pain: Mild
    3.4 (1.1 to 7.9)
    3.4 (1.1 to 7.7)
    1.8 (0 to 9.7)
    7.8 (2.2 to 18.9)
    3.4 (1.6 to 6.2)
    4.7 (1.5 to 10.7)
        Joint pain: Moderate
    2.8 (0.8 to 6.9)
    3.4 (1.1 to 7.7)
    0 (0 to 6.5)
    0 (0 to 7)
    3.1 (1.4 to 5.7)
    0 (0 to 3.4)
        Joint pain: Severe
    0 (0 to 2.5)
    0 (0 to 2.4)
    0 (0 to 6.5)
    0 (0 to 7)
    0 (0 to 1.2)
    0 (0 to 3.4)
        Antipyretic Medication Use
    42.8 (34.6 to 51.2)
    31.5 (24.2 to 39.7)
    14.5 (6.5 to 26.7)
    17.6 (8.4 to 30.9)
    37.1 (31.5 to 42.9)
    16 (9.6 to 24.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 2 [6]
    End point description
    Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, >39.5 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily activity). Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 Days after Vaccination 2
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    143
    148
    54
    49
    291
    103
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever >=38 degrees C
    15.4 (9.9 to 22.4)
    8.8 (4.8 to 14.6)
    3.7 (0.5 to 12.7)
    2 (0.1 to 10.9)
    12 (8.5 to 16.3)
    2.9 (0.6 to 8.3)
        Fever 38 to <38.5 degrees C
    7.7 (3.9 to 13.3)
    5.4 (2.4 to 10.4)
    3.7 (0.5 to 12.7)
    0 (0 to 7.3)
    6.5 (4 to 10)
    1.9 (0.2 to 6.8)
        Fever 38.5 to <39 degrees C
    2.8 (0.8 to 7)
    0.7 (0 to 3.7)
    0 (0 to 6.6)
    2 (0.1 to 10.9)
    1.7 (0.6 to 4)
    1 (0 to 5.3)
        Fever 39 to <39.5 degrees C
    1.4 (0.2 to 5)
    2 (0.4 to 5.8)
    0 (0 to 6.6)
    0 (0 to 7.3)
    1.7 (0.6 to 4)
    0 (0 to 3.5)
        Fever 39.5 to 40 degrees C
    2.8 (0.8 to 7)
    0.7 (0 to 3.7)
    0 (0 to 6.6)
    0 (0 to 7.3)
    1.7 (0.6 to 4)
    0 (0 to 3.5)
        Fever >40 degrees C
    0.7 (0 to 3.8)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    0.3 (0 to 1.9)
    0 (0 to 3.5)
        Vomiting: Any
    5.6 (2.4 to 10.7)
    4.7 (1.9 to 9.5)
    3.7 (0.5 to 12.7)
    6.1 (1.3 to 16.9)
    5.2 (2.9 to 8.4)
    4.9 (1.6 to 11)
        Vomiting: Mild
    4.2 (1.6 to 8.9)
    2.7 (0.7 to 6.8)
    1.9 (0 to 9.9)
    6.1 (1.3 to 16.9)
    3.4 (1.7 to 6.2)
    3.9 (1.1 to 9.6)
        Vomiting: Moderate
    1.4 (0.2 to 5)
    2 (0.4 to 5.8)
    1.9 (0 to 9.9)
    0 (0 to 7.3)
    1.7 (0.6 to 4)
    1 (0 to 5.3)
        Vomiting: Severe
    0 (0 to 2.5)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    0 (0 to 1.3)
    0 (0 to 3.5)
        Diarrhea: Any
    9.8 (5.5 to 15.9)
    6.8 (3.3 to 12.1)
    5.6 (1.2 to 15.4)
    6.1 (1.3 to 16.9)
    8.2 (5.4 to 12)
    5.8 (2.2 to 12.2)
        Diarrhea: Mild
    8.4 (4.4 to 14.2)
    6.8 (3.3 to 12.1)
    5.6 (1.2 to 15.4)
    6.1 (1.3 to 16.9)
    7.6 (4.8 to 11.2)
    5.8 (2.2 to 12.2)
        Diarrhea: Moderate
    0.7 (0 to 3.8)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    0.3 (0 to 1.9)
    0 (0 to 3.5)
        Diarrhea: Severe
    0.7 (0 to 3.8)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    0.3 (0 to 1.9)
    0 (0 to 3.5)
        Headache: Any
    11.2 (6.5 to 17.5)
    25 (18.3 to 32.8)
    1.9 (0 to 9.9)
    22.4 (11.8 to 36.6)
    18.2 (14 to 23.1)
    11.7 (6.2 to 19.5)
        Headache: Mild
    7.7 (3.9 to 13.3)
    12.8 (7.9 to 19.3)
    1.9 (0 to 9.9)
    18.4 (8.8 to 32)
    10.3 (7.1 to 14.4)
    9.7 (4.8 to 17.1)
        Headache: Moderate
    3.5 (1.1 to 8)
    11.5 (6.8 to 17.8)
    0 (0 to 6.6)
    2 (0.1 to 10.9)
    7.6 (4.8 to 11.2)
    1 (0 to 5.3)
        Headache: Severe
    0 (0 to 2.5)
    0.7 (0 to 3.7)
    0 (0 to 6.6)
    2 (0.1 to 10.9)
    0.3 (0 to 1.9)
    1 (0 to 5.3)
        Fatigue: Any
    45.5 (37.1 to 54)
    41.2 (33.2 to 49.6)
    13 (5.4 to 24.9)
    14.3 (5.9 to 27.2)
    43.3 (37.5 to 49.2)
    13.6 (7.6 to 21.8)
        Fatigue: Mild
    22.4 (15.8 to 30.1)
    19.6 (13.5 to 26.9)
    7.4 (2.1 to 17.9)
    8.2 (2.3 to 19.6)
    21 (16.4 to 26.1)
    7.8 (3.4 to 14.7)
        Fatigue: Moderate
    19.6 (13.4 to 27)
    19.6 (13.5 to 26.9)
    5.6 (1.2 to 15.4)
    6.1 (1.3 to 16.9)
    19.6 (15.2 to 24.6)
    5.8 (2.2 to 12.2)
        Fatigue: Severe
    3.5 (1.1 to 8)
    2 (0.4 to 5.8)
    0 (0 to 6.6)
    0 (0 to 7.3)
    2.7 (1.2 to 5.3)
    0 (0 to 3.5)
        Muscle pain: Any
    11.2 (6.5 to 17.5)
    14.9 (9.6 to 21.6)
    0 (0 to 6.6)
    4.1 (0.5 to 14)
    13.1 (9.4 to 17.5)
    1.9 (0.2 to 6.8)
        Muscle pain: Mild
    3.5 (1.1 to 8)
    10.1 (5.8 to 16.2)
    0 (0 to 6.6)
    4.1 (0.5 to 14)
    6.9 (4.2 to 10.4)
    1.9 (0.2 to 6.8)
        Muscle pain: Moderate
    7 (3.4 to 12.5)
    4.7 (1.9 to 9.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    5.8 (3.4 to 9.2)
    0 (0 to 3.5)
        Muscle pain: Severe
    0.7 (0 to 3.8)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    0.3 (0 to 1.9)
    0 (0 to 3.5)
        Joint pain: Any
    5.6 (2.4 to 10.7)
    8.8 (4.8 to 14.6)
    0 (0 to 6.6)
    8.2 (2.3 to 19.6)
    7.2 (4.5 to 10.8)
    3.9 (1.1 to 9.6)
        Joint pain: Mild
    1.4 (0.2 to 5)
    4.1 (1.5 to 8.6)
    0 (0 to 6.6)
    8.2 (2.3 to 19.6)
    2.7 (1.2 to 5.3)
    3.9 (1.1 to 9.6)
        Joint pain: Moderate
    2.1 (0.4 to 6)
    4.7 (1.9 to 9.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    3.4 (1.7 to 6.2)
    0 (0 to 3.5)
        Joint pain: Severe
    2.1 (0.4 to 6)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.3)
    1 (0.2 to 3)
    0 (0 to 3.5)
        Antipyretic Medication Use
    32.9 (25.2 to 41.2)
    27 (20.1 to 34.9)
    1.9 (0 to 9.9)
    10.2 (3.4 to 22.2)
    29.9 (24.7 to 35.5)
    5.8 (2.2 to 12.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 3 [7]
    End point description
    Systemic reactions included fever, vomiting, diarrhea, headache, fatigue, muscle and joint pain (other than at the injection site) and recorded by using an e-diary. Fever was graded as 38.0 to 38.4 degree C, 38.5 to 38.9 degree C, 39.0 to 39.4 degree C, >39.5 to 40.0 degree C and >40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily activity). Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 7 Days after Vaccination 3
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    139
    146
    54
    50
    285
    104
    Units: Percentage of subjects
    number (confidence interval 95%)
        Fever >=38 degrees C
    11.5 (6.7 to 18)
    2.1 (0.4 to 5.9)
    9.3 (3.1 to 20.3)
    2 (0.1 to 10.6)
    6.7 (4.1 to 10.2)
    5.8 (2.1 to 12.1)
        Fever 38 to <38.5 degrees C
    5 (2 to 10.1)
    2.1 (0.4 to 5.9)
    3.7 (0.5 to 12.7)
    2 (0.1 to 10.6)
    3.5 (1.7 to 6.4)
    2.9 (0.6 to 8.2)
        Fever 38.5 to <39 degrees C
    3.6 (1.2 to 8.2)
    0 (0 to 2.5)
    3.7 (0.5 to 12.7)
    0 (0 to 7.1)
    1.8 (0.6 to 4)
    1.9 (0.2 to 6.8)
        Fever 39 to <39.5 degrees C
    2.2 (0.4 to 6.2)
    0 (0 to 2.5)
    1.9 (0 to 9.9)
    0 (0 to 7.1)
    1.1 (0.2 to 3)
    1 (0 to 5.2)
        Fever 39.5 to 40 degrees C
    0.7 (0 to 3.9)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.4 (0 to 1.9)
    0 (0 to 3.5)
        Fever >40 degrees C
    0 (0 to 2.6)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0 (0 to 1.3)
    0 (0 to 3.5)
        Vomiting: Any
    4.3 (1.6 to 9.2)
    2.1 (0.4 to 5.9)
    5.6 (1.2 to 15.4)
    2 (0.1 to 10.6)
    3.2 (1.5 to 5.9)
    3.8 (1.1 to 9.6)
        Vomiting: Mild
    2.9 (0.8 to 7.2)
    1.4 (0.2 to 4.9)
    3.7 (0.5 to 12.7)
    0 (0 to 7.1)
    2.1 (0.8 to 4.5)
    1.9 (0.2 to 6.8)
        Vomiting: Moderate
    1.4 (0.2 to 5.1)
    0.7 (0 to 3.8)
    1.9 (0 to 9.9)
    2 (0.1 to 10.6)
    1.1 (0.2 to 3)
    1.9 (0.2 to 6.8)
        Vomiting: Severe
    0 (0 to 2.6)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0 (0 to 1.3)
    0 (0 to 3.5)
        Diarrhea: Any
    6.5 (3 to 11.9)
    6.2 (2.9 to 11.4)
    3.7 (0.5 to 12.7)
    2 (0.1 to 10.6)
    6.3 (3.8 to 9.8)
    2.9 (0.6 to 8.2)
        Diarrhea: Mild
    5.8 (2.5 to 11)
    4.8 (1.9 to 9.6)
    3.7 (0.5 to 12.7)
    2 (0.1 to 10.6)
    5.3 (3 to 8.5)
    2.9 (0.6 to 8.2)
        Diarrhea: Moderate
    0.7 (0 to 3.9)
    0.7 (0 to 3.8)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.7 (0.1 to 2.5)
    0 (0 to 3.5)
        Diarrhea: Severe
    0 (0 to 2.6)
    0.7 (0 to 3.8)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.4 (0 to 1.9)
    0 (0 to 3.5)
        Headache: Any
    7.2 (3.5 to 12.8)
    20.5 (14.3 to 28)
    1.9 (0 to 9.9)
    12 (4.5 to 24.3)
    14 (10.2 to 18.6)
    6.7 (2.7 to 13.4)
        Headache: Mild
    5.8 (2.5 to 11)
    15.1 (9.7 to 21.9)
    0 (0 to 6.6)
    8 (2.2 to 19.2)
    10.5 (7.2 to 14.7)
    3.8 (1.1 to 9.6)
        Headache: Moderate
    1.4 (0.2 to 5.1)
    5.5 (2.4 to 10.5)
    1.9 (0 to 9.9)
    4 (0.5 to 13.7)
    3.5 (1.7 to 6.4)
    2.9 (0.6 to 8.2)
        Headache: Severe
    0 (0 to 2.6)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0 (0 to 1.3)
    0 (0 to 3.5)
        Fatigue: Any
    36 (28 to 44.5)
    30.8 (23.5 to 39)
    18.5 (9.3 to 31.4)
    16 (7.2 to 29.1)
    33.3 (27.9 to 39.1)
    17.3 (10.6 to 26)
        Fatigue: Mild
    16.5 (10.8 to 23.8)
    19.9 (13.7 to 27.3)
    11.1 (4.2 to 22.6)
    12 (4.5 to 24.3)
    18.2 (13.9 to 23.2)
    11.5 (6.1 to 19.3)
        Fatigue: Moderate
    18 (12 to 25.4)
    10.3 (5.9 to 16.4)
    7.4 (2.1 to 17.9)
    4 (0.5 to 13.7)
    14 (10.2 to 18.6)
    5.8 (2.1 to 12.1)
        Fatigue: Severe
    1.4 (0.2 to 5.1)
    0.7 (0 to 3.8)
    0 (0 to 6.6)
    0 (0 to 7.1)
    1.1 (0.2 to 3)
    0 (0 to 3.5)
        Muscle pain: Any
    12.9 (7.9 to 19.7)
    11.6 (6.9 to 18)
    5.6 (1.2 to 15.4)
    4 (0.5 to 13.7)
    12.3 (8.7 to 16.7)
    4.8 (1.6 to 10.9)
        Muscle pain: Mild
    7.2 (3.5 to 12.8)
    5.5 (2.4 to 10.5)
    1.9 (0 to 9.9)
    4 (0.5 to 13.7)
    6.3 (3.8 to 9.8)
    2.9 (0.6 to 8.2)
        Muscle pain: Moderate
    5 (2 to 10.1)
    6.2 (2.9 to 11.4)
    3.7 (0.5 to 12.7)
    0 (0 to 7.1)
    5.6 (3.2 to 9)
    1.9 (0.2 to 6.8)
        Muscle pain: Severe
    0.7 (0 to 3.9)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.4 (0 to 1.9)
    0 (0 to 3.5)
        Joint pain: Any
    7.2 (3.5 to 12.8)
    7.5 (3.8 to 13.1)
    0 (0 to 6.6)
    6 (1.3 to 16.5)
    7.4 (4.6 to 11)
    2.9 (0.6 to 8.2)
        Joint pain: Mild
    2.9 (0.8 to 7.2)
    4.8 (1.9 to 9.6)
    0 (0 to 6.6)
    6 (1.3 to 16.5)
    3.9 (1.9 to 6.8)
    2.9 (0.6 to 8.2)
        Joint pain: Moderate
    3.6 (1.2 to 8.2)
    2.7 (0.8 to 6.9)
    0 (0 to 6.6)
    0 (0 to 7.1)
    3.2 (1.5 to 5.9)
    0 (0 to 3.5)
        Joint pain: Severe
    0.7 (0 to 3.9)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.4 (0 to 1.9)
    0 (0 to 3.5)
        Antipyretic Medication Use
    25.2 (18.2 to 33.2)
    27.4 (20.3 to 35.4)
    13 (5.4 to 24.9)
    8 (2.2 to 19.2)
    26.3 (21.3 to 31.8)
    10.6 (5.4 to 18.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 1 [8]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 1
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    0.7 (0 to 3.8)
    0 (0 to 2.4)
    1.8 (0 to 9.7)
    0 (0 to 7)
    0.3 (0 to 1.9)
    0.9 (0 to 5.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 2 [9]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 2
    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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    143
    148
    54
    50
    291
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    1.4 (0.2 to 5)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.7 (0.1 to 2.5)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Vaccination 3 [10]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 3
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    140
    147
    54
    50
    287
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 2.6)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0 (0 to 1.3)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Any Vaccination

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Within 30 Days After Any Vaccination [11]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    Within 30 Days after any vaccination
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    2.1 (0.4 to 5.9)
    0 (0 to 2.4)
    1.8 (0 to 9.7)
    0 (0 to 7)
    1 (0.2 to 3)
    0.9 (0 to 5.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Vaccination Phase [12]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 1 month after Vaccination 3
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    2.1 (0.4 to 5.9)
    0.7 (0 to 3.7)
    1.8 (0 to 9.7)
    0 (0 to 7)
    1.4 (0.4 to 3.4)
    0.9 (0 to 5.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) During the Follow-up Phase [13]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Safety population included all subjects who had at least 1 dose of investigational product (rLP2086 or HAV/saline) and had safety data available from after post third-vaccination blood draw to 6 months after last study vaccination. Here "N" signifies number of subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    From 1 month after Vaccination 3 up to 6 months after Vaccination 3
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    137
    147
    54
    50
    284
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 2.7)
    0.7 (0 to 3.7)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.4 (0 to 1.9)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Throughout the Study

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) Throughout the Study [14]
    End point description
    SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; lack of efficacy in an approved indication. An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From Vaccination 1 up to 6 months after Vaccination 3
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    2.1 (0.4 to 5.9)
    1.3 (0.2 to 4.8)
    1.8 (0 to 9.7)
    0 (0 to 7)
    1.7 (0.6 to 3.9)
    0.9 (0 to 5.1)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 1 [15]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 1
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    18.6 (12.6 to 25.9)
    8.1 (4.2 to 13.6)
    16.4 (7.8 to 28.8)
    9.8 (3.3 to 21.4)
    13.3 (9.6 to 17.7)
    13.2 (7.4 to 21.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 2 [16]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 2
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    143
    148
    54
    50
    291
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    10.5 (6 to 16.7)
    13.5 (8.5 to 20.1)
    14.8 (6.6 to 27.1)
    8 (2.2 to 19.2)
    12 (8.5 to 16.3)
    11.5 (6.1 to 19.3)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After Vaccination 3 [17]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 3
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    140
    147
    54
    50
    287
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    6.4 (3 to 11.9)
    4.8 (1.9 to 9.6)
    5.6 (1.2 to 15.4)
    4 (0.5 to 13.7)
    5.6 (3.2 to 8.9)
    4.8 (1.6 to 10.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After any Vaccination

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Within 30 Days After any Vaccination [18]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    Within 30 Days after any vaccination
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    29 (21.7 to 37.1)
    22.8 (16.3 to 30.4)
    30.9 (19.1 to 44.8)
    21.6 (11.3 to 35.3)
    25.9 (20.9 to 31.3)
    26.4 (18.3 to 35.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) During the Vaccination Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) During the Vaccination Phase [19]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 1 month after the Vaccination 3
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    45.5 (37.2 to 54)
    40.9 (33 to 49.3)
    41.8 (28.7 to 55.9)
    51 (36.6 to 65.2)
    43.2 (37.5 to 49.1)
    46.2 (36.5 to 56.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) During the Follow-up Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) During the Follow-up Phase [20]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Safety population included all subjects who had at least 1 dose of investigational product (rLP2086 or HAV/saline) and had safety data available from after post third-vaccination blood draw to 6 months after last study vaccination. Here "N" signifies number of subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    From 1 month after Vaccination 3 up to 6 months after the Vaccination 3
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    137
    147
    54
    50
    284
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    20.4 (14 to 28.2)
    16.3 (10.7 to 23.3)
    13 (5.4 to 24.9)
    12 (4.5 to 24.3)
    18.3 (14 to 23.3)
    12.5 (6.8 to 20.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Throughout the Study

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Medically Attended Adverse Event (AE) Throughout the Study [21]
    End point description
    A medically attended AE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 6 month after the Vaccination 3
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    49 (40.6 to 57.4)
    48.3 (40.1 to 56.6)
    47.3 (33.7 to 61.2)
    52.9 (38.5 to 67.1)
    48.6 (42.8 to 54.5)
    50 (40.1 to 59.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 1 [22]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 1
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 2 [23]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 2
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After Vaccination 3 [24]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 3
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After any Vaccination

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Within 30 Days After any Vaccination [25]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    Within 30 Days after any vaccination
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Vaccination Phase [26]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 1 month after the Vaccination 3
    Notes
    [26] - 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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-up Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition During the Follow-up Phase [27]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Safety population included all subjects who had at least 1 dose of investigational product (rLP2086 or HAV/saline) and had safety data available from after post third-vaccination blood draw to 6 months after last study vaccination.
    End point type
    Primary
    End point timeframe
    From 1 month after Vaccination 3 up to 6 months after the Vaccination 3
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition Throughout the Study [28]
    End point description
    A newly diagnosed chronic medical condition was defined as a disease or medical condition that was not identified prior to study start and was expected to be persistent or otherwise long-lasting in its effects. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 6 month after the Vaccination 3
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (not applicable)
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 1 [29]
    End point description
    AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 1
    Notes
    [29] - 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: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    29 (21.7 to 37.1)
    19.5 (13.4 to 26.7)
    21.8 (11.8 to 35)
    13.7 (5.7 to 26.3)
    24.1 (19.4 to 29.5)
    17.9 (11.2 to 26.6)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 2 [30]
    End point description
    AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 2
    Notes
    [30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    143
    148
    54
    50
    291
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    19.6 (13.4 to 27)
    26.4 (19.5 to 34.2)
    27.8 (16.5 to 41.6)
    16 (7.2 to 29.1)
    23 (18.3 to 28.3)
    22.1 (14.6 to 31.3)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After Vaccination 3 [31]
    End point description
    AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 Days after Vaccination 3
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    140
    147
    54
    50
    287
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    12.9 (7.8 to 19.6)
    15.6 (10.2 to 22.5)
    11.1 (4.2 to 22.6)
    8 (2.2 to 19.2)
    14.3 (10.5 to 18.9)
    9.6 (4.7 to 17)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After any Vaccination

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE) Within 30 Days After any Vaccination [32]
    End point description
    AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    Within 30 Days after any vaccination
    Notes
    [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    44.8 (36.6 to 53.3)
    43.6 (35.5 to 52)
    49.1 (35.4 to 62.9)
    29.4 (17.5 to 43.8)
    44.2 (38.5 to 50.1)
    39.6 (30.3 to 49.6)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE) During the Vaccination Phase

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE) During the Vaccination Phase [33]
    End point description
    AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 1 month after the Vaccination 3
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    62.1 (53.6 to 70)
    63.1 (54.8 to 70.8)
    63.6 (49.6 to 76.2)
    62.7 (48.1 to 75.9)
    62.6 (56.8 to 68.1)
    63.2 (53.3 to 72.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Vaccination 1

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Vaccination 1 [34]
    End point description
    Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Vaccination 1 safety population included all subjects who received the first dose of investigational products (rLP2086 or HAV vaccine) on Day 1 (Month 0).
    End point type
    Primary
    End point timeframe
    Within 30 minutes after Vaccination 1
    Notes
    [34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 2.5)
    0 (0 to 2.4)
    0 (0 to 6.5)
    0 (0 to 7)
    0 (0 to 1.2)
    0 (0 to 3.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Vaccination 2

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Vaccination 2 [35]
    End point description
    Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Vaccination 2 safety population included all subjects who received the second dose of investigational products (rLP2086 or saline) on Month 2 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 minutes after Vaccination 2
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    143
    148
    54
    50
    291
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 2.5)
    0 (0 to 2.5)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0 (0 to 1.3)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Vaccination 3 [36]
    End point description
    Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Vaccination 3 safety population included all subjects who received the third dose of investigational product (rLP2086 or HAV vaccine) on Month 6 visit. Here "N" signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Within 30 minutes after Vaccination 3
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    140
    147
    54
    50
    287
    104
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 2.6)
    0.7 (0 to 3.7)
    0 (0 to 6.6)
    0 (0 to 7.1)
    0.3 (0 to 1.9)
    0 (0 to 3.5)
    No statistical analyses for this end point

    Primary: Number of Days Subject's Missed School Due to Adverse Event (AE) During the Vaccination Phase

    		 Close Top of page
    End point title
    		 Number of Days Subject's Missed School Due to Adverse Event (AE) During the Vaccination Phase [37]
    End point description
    Safety population included all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available.
    End point type
    Primary
    End point timeframe
    From the Vaccination 1 up to 1 month after the Vaccination 3
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    145
    149
    55
    51
    294
    106
    Units: Days
        arithmetic mean (standard deviation)
    7 ( 3.7 )
    4 ( 2.6 )
    7.3 ( 2.3 )
    4.2 ( 2.5 )
    4.7 ( 3.1 )
    4.6 ( 2.6 )
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged >=24 Months to <10 Years With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects Aged >=24 Months to <10 Years With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 3
    End point description
    Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24) and PMB2707 (B44). Evaluable immunogenicity population included all eligible subjects randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, ‘’n’’ signifies number of subjects evaluable for the specified test strain.
    End point type
    Secondary
    End point timeframe
    1 Month after Vaccination 3
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    274
    97
    Units: Percentage of subjects
    number (confidence interval 95%)
        PMB80 [A22] (n = 135, 45)
    87.4 (80.6 to 92.5)
    6.7 (1.4 to 18.3)
        PMB2001 [A56] (n = 139, 43)
    100 (97.4 to 100)
    20.9 (10 to 36)
        PMB2948 [B24] (n = 126, 46)
    88.9 (82.1 to 93.8)
    4.3 (0.5 to 14.8)
        PMB2707 [B44] (n = 134, 50)
    79.1 (71.2 to 85.6)
    0 (0 to 7.1)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 2 and 6 Months After Vaccination 3

    		 Close Top of page
    End point title
    		 Percentage of Subjects With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 2 and 6 Months After Vaccination 3
    End point description
    Percentage of subjects achieving hSBA titer >= LLOQ were computed along with corresponding 2-sided 95% CIs. LLOQ was 1:16 for PMB80 (A22) and 1:8 for PMB2001 (A56), PMB2948 (B24), and PMB2707 (B44). Evaluable immunogenicity population included all eligible subjects randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, "n" signifies number of subjects evaluable for the specified categories.
    End point type
    Secondary
    End point timeframe
    1 month (Mon) after Vaccination (Vac) 2 and 6 months after Vaccination 3
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    136
    138
    52
    45
    274
    97
    Units: Percentage of subjects
    number (confidence interval 95%)
        1 Mon after Vac2: PMB80[A22](n=64,66,24,21,130,45)
    59.4 (46.4 to 71.5)
    78.8 (67 to 87.9)
    0 (0 to 14.2)
    9.5 (1.2 to 30.4)
    69.2 (60.5 to 77)
    4.4 (0.5 to 15.1)
        6 Mon after Vac3: PMB80[A22](n=63,63,26,21,126,47)
    19 (10.2 to 30.9)
    46 (33.4 to 59.1)
    7.7 (0.9 to 25.1)
    9.5 (1.2 to 30.4)
    32.5 (24.5 to 41.5)
    8.5 (2.4 to 20.4)
        1Mon after Vac2:PMB2001[A56](n=66,67,21,22,133,43)
    100 (94.6 to 100)
    100 (94.6 to 100)
    9.5 (1.2 to 30.4)
    22.7 (7.8 to 45.4)
    100 (97.3 to 100)
    16.3 (6.8 to 30.7)
        6Mon after Vac3:PMB2001[A56](n=61,70,24,22,131,46)
    80.3 (68.2 to 89.4)
    84.3 (73.6 to 91.9)
    16.7 (4.7 to 37.4)
    22.7 (7.8 to 45.4)
    82.4 (74.8 to 88.5)
    19.6 (9.4 to 33.9)
        1Mon after Vac2:PMB2948[B24](n=65,63,24,21,128,45)
    49.2 (36.6 to 61.9)
    65.1 (52 to 76.7)
    8.3 (1 to 27)
    9.5 (1.2 to 30.4)
    57 (48 to 65.7)
    8.9 (2.5 to 21.2)
        6Mon after Vac3:PMB2948[B24](n=65,64,26,21,129,47)
    9.2 (3.5 to 19)
    21.9 (12.5 to 34)
    0 (0 to 13.2)
    0 (0 to 16.1)
    15.5 (9.7 to 22.9)
    0 (0 to 7.5)
        1Mon after Vac2:PMB2707[B44](n=63,67,26,24,130,50)
    57.1 (44 to 69.5)
    40.3 (28.5 to 53)
    0 (0 to 13.2)
    0 (0 to 14.2)
    48.5 (39.6 to 57.4)
    0 (0 to 7.1)
        6Mon after Vac3:PMB2707[B44](n=66,69,26,23,135,49)
    12.1 (5.4 to 22.5)
    8.7 (3.3 to 18)
    0 (0 to 13.2)
    0 (0 to 14.8)
    10.4 (5.8 to 16.8)
    0 (0 to 7.3)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Serum Bactericidal Assay Using hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64 and >=1:128 for Each of the 4 Primary Test Strains

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Serum Bactericidal Assay Using hSBA Titers >=1:4, >=1:8, >=1:16, >=1:32, >=1:64 and >=1:128 for Each of the 4 Primary Test Strains
    End point description
    Evaluable immunogenicity population included all eligible subjects randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, "n" signifies number of subjects evaluable for the specified categories.
    End point type
    Secondary
    End point timeframe
    Before Vaccination 1 (T1), 1 month after Vaccination 2 (T2), 1 month after Vaccination 3 (T3) and 6 months after Vaccination 3 (T4)
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    136
    138
    52
    45
    274
    97
    Units: Percentage of subjects
    number (confidence interval 95%)
        T1: PMB80 [A22] - 1:4 (n=68,66,26,21,134,47)
    5.9 (1.6 to 14.4)
    19.7 (10.9 to 31.3)
    3.8 (0.1 to 19.6)
    9.5 (1.2 to 30.4)
    12.7 (7.6 to 19.5)
    6.4 (1.3 to 17.5)
        T1: PMB80 [A22] - 1:8 (n=68,66,26,21,134,47)
    5.9 (1.6 to 14.4)
    18.2 (9.8 to 29.6)
    3.8 (0.1 to 19.6)
    9.5 (1.2 to 30.4)
    11.9 (7 to 18.7)
    6.4 (1.3 to 17.5)
        T1: PMB80 [A22] - 1:16 (n=68,66,26,21,134,47)
    4.4 (0.9 to 12.4)
    13.6 (6.4 to 24.3)
    3.8 (0.1 to 19.6)
    9.5 (1.2 to 30.4)
    9 (4.7 to 15.1)
    6.4 (1.3 to 17.5)
        T1: PMB80 [A22] - 1:32 (n=68,66,26,21,134,47)
    1.5 (0 to 7.9)
    4.5 (0.9 to 12.7)
    0 (0 to 13.2)
    9.5 (1.2 to 30.4)
    3 (0.8 to 7.5)
    4.3 (0.5 to 14.5)
        T1: PMB80 [A22] - 1:64 (n=68,66,26,21,134,47)
    0 (0 to 5.3)
    0 (0 to 5.4)
    0 (0 to 13.2)
    4.8 (0.1 to 23.8)
    0 (0 to 2.7)
    2.1 (0.1 to 11.3)
        T1: PMB80 [A22] - 1:128 (n=68,66,26,21,134,47)
    0 (0 to 5.3)
    0 (0 to 5.4)
    0 (0 to 13.2)
    4.8 (0.1 to 23.8)
    0 (0 to 2.7)
    2.1 (0.1 to 11.3)
        T2: PMB80 [A22] - 1:4 (n=64,66,24,21,130,45)
    65.6 (52.7 to 77.1)
    83.3 (72.1 to 91.4)
    8.3 (1 to 27)
    14.3 (3 to 36.3)
    74.6 (66.2 to 81.8)
    11.1 (3.7 to 24.1)
        T2: PMB80 [A22] - 1:8 (n=64,66,24,21,130,45)
    62.5 (49.5 to 74.3)
    81.8 (70.4 to 90.2)
    8.3 (1 to 27)
    9.5 (1.2 to 30.4)
    72.3 (63.8 to 79.8)
    8.9 (2.5 to 21.2)
        T2: PMB80 [A22] - 1:32 (n=64,66,24,21,130,45)
    35.9 (24.3 to 48.9)
    47 (34.6 to 59.7)
    0 (0 to 14.2)
    9.5 (1.2 to 30.4)
    41.5 (33 to 50.5)
    4.4 (0.5 to 15.1)
        T2: PMB80 [A22] - 1:64 (n=64,66,24,21,130,45)
    14.1 (6.6 to 25)
    19.7 (10.9 to 31.3)
    0 (0 to 14.2)
    4.8 (0.1 to 23.8)
    16.9 (10.9 to 24.5)
    2.2 (0.1 to 11.8)
        T2: PMB80 [A22] - 1:128 (n=64,66,24,21,130,45)
    1.6 (0 to 8.4)
    7.6 (2.5 to 16.8)
    0 (0 to 14.2)
    0 (0 to 16.1)
    4.6 (1.7 to 9.8)
    0 (0 to 7.9)
        T3: PMB80 [A22] - 1:4 (n=68,67,25,20,135,45)
    86.8 (76.4 to 93.8)
    98.5 (92 to 100)
    8 (1 to 26)
    15 (3.2 to 37.9)
    92.6 (86.8 to 96.4)
    11.1 (3.7 to 24.1)
        T3: PMB80 [A22] - 1:8 (n=68,67,25,20,135,45)
    86.8 (76.4 to 93.8)
    98.5 (92 to 100)
    8 (1 to 26)
    15 (3.2 to 37.9)
    92.6 (86.8 to 96.4)
    11.1 (3.7 to 24.1)
        T3: PMB80 [A22] - 1:32 (n=68,67,25,20,135,45)
    63.2 (50.7 to 74.6)
    71.6 (59.3 to 82)
    4 (0.1 to 20.4)
    5 (0.1 to 24.9)
    67.4 (58.8 to 75.2)
    4.4 (0.5 to 15.1)
        T3: PMB80 [A22] - 1:64 (n=68,67,25,20,135,45)
    38.2 (26.7 to 50.8)
    40.3 (28.5 to 53)
    4 (0.1 to 20.4)
    0 (0 to 16.8)
    39.3 (31 to 48)
    2.2 (0.1 to 11.8)
        T3:PMB80 [A22] - 1:128 (n=68,67,25,20,135,45)
    14.7 (7.3 to 25.4)
    16.4 (8.5 to 27.5)
    0 (0 to 13.7)
    0 (0 to 16.8)
    15.6 (9.9 to 22.8)
    0 (0 to 7.9)
        T4: PMB80 [A22] - 1:4 (n=63,63,26,21,126,47)
    25.4 (15.3 to 37.9)
    55.6 (42.5 to 68.1)
    11.5 (2.4 to 30.2)
    9.5 (1.2 to 30.4)
    40.5 (31.8 to 49.6)
    10.6 (3.5 to 23.1)
        T4: PMB80 [A22] - 1:8 (n=63,63,26,21,126,47)
    22.2 (12.7 to 34.5)
    55.6 (42.5 to 68.1)
    7.7 (0.9 to 25.1)
    9.5 (1.2 to 30.4)
    38.9 (30.3 to 48)
    8.5 (2.4 to 20.4)
        T4: PMB80 [A22] - 1:32 (n=63,63,26,21,126,47)
    14.3 (6.7 to 25.4)
    25.4 (15.3 to 37.9)
    0 (0 to 13.2)
    4.8 (0.1 to 23.8)
    19.8 (13.3 to 27.9)
    2.1 (0.1 to 11.3)
        T4: PMB80 [A22] - 1:64 (n=63,63,26,21,126,47)
    4.8 (1 to 13.3)
    11.1 (4.6 to 21.6)
    0 (0 to 13.2)
    4.8 (0.1 to 23.8)
    7.9 (3.9 to 14.1)
    2.1 (0.1 to 11.3)
        T4: PMB80 [A22] - 1:128 (n=63,63,26,21,126,47)
    4.8 (1 to 13.3)
    0 (0 to 5.7)
    0 (0 to 13.2)
    0 (0 to 16.1)
    2.4 (0.5 to 6.8)
    0 (0 to 7.5)
        T1: PMB2001 [A56] - 1:4 (n=67,65,24,23,132,47)
    3 (0.4 to 10.4)
    18.5 (9.9 to 30)
    16.7 (4.7 to 37.4)
    21.7 (7.5 to 43.7)
    10.6 (5.9 to 17.2)
    19.1 (9.1 to 33.3)
        T1: PMB2001 [A56] - 1:8 (n=67,65,24,23,132,47)
    1.5 (0 to 8)
    15.4 (7.6 to 26.5)
    8.3 (1 to 27)
    21.7 (7.5 to 43.7)
    8.3 (4.2 to 14.4)
    14.9 (6.2 to 28.3)
        T1: PMB2001 [A56] - 1:16 (n=67,65,24,23,132,47)
    1.5 (0 to 8)
    15.4 (7.6 to 26.5)
    8.3 (1 to 27)
    21.7 (7.5 to 43.7)
    8.3 (4.2 to 14.4)
    14.9 (6.2 to 28.3)
        T1: PMB2001 [A56] - 1:32 (n=67,65,24,23,132,47)
    0 (0 to 5.4)
    13.8 (6.5 to 24.7)
    8.3 (1 to 27)
    17.4 (5 to 38.8)
    6.8 (3.2 to 12.5)
    12.8 (4.8 to 25.7)
        T1: PMB2001 [A56] - 1:64 (n=67,65,24,23,132,47)
    0 (0 to 5.4)
    7.7 (2.5 to 17)
    4.2 (0.1 to 21.1)
    8.7 (1.1 to 28)
    3.8 (1.2 to 8.6)
    6.4 (1.3 to 17.5)
        T1: PMB2001 [A56] -1:128 (n=67,65,24,23,132,47)
    0 (0 to 5.4)
    1.5 (0 to 8.3)
    0 (0 to 14.2)
    0 (0 to 14.8)
    0.8 (0 to 4.1)
    0 (0 to 7.5)
        T2: PMB2001 [A56] - 1:4 (n=66,67,21,22,133,43)
    100 (94.6 to 100)
    100 (94.6 to 100)
    9.5 (1.2 to 30.4)
    22.7 (7.8 to 45.4)
    100 (97.3 to 100)
    16.3 (6.8 to 30.7)
        T2: PMB2001 [A56] - 1:16 (n=66,67,21,22,133,43)
    100 (94.6 to 100)
    98.5 (92 to 100)
    9.5 (1.2 to 30.4)
    22.7 (7.8 to 45.4)
    99.2 (95.9 to 100)
    16.3 (6.8 to 30.7)
        T2: PMB2001 [A56] - 1:32 (n=66,67,21,22,133,43)
    97 (89.5 to 99.6)
    92.5 (83.4 to 97.5)
    9.5 (1.2 to 30.4)
    13.6 (2.9 to 34.9)
    94.7 (89.5 to 97.9)
    11.6 (3.9 to 25.1)
        T2: PMB2001 [A56] - 1:64 (n=66,67,21,22,133,43)
    80.3 (68.7 to 89.1)
    82.1 (70.8 to 90.4)
    4.8 (0.1 to 23.8)
    9.1 (1.1 to 29.2)
    81.2 (73.5 to 87.5)
    7 (1.5 to 19.1)
        T2: PMB2001 [A56] - 1:128 (n=66,67,21,22,133,43)
    62.1 (49.3 to 73.8)
    46.3 (34 to 58.9)
    0 (0 to 16.1)
    4.5 (0.1 to 22.8)
    54.1 (45.3 to 62.8)
    2.3 (0.1 to 12.3)
        T3: PMB2001 [A56] - 1:4 (n=68,71,24,19,139,43)
    100 (94.7 to 100)
    100 (94.9 to 100)
    4.2 (0.1 to 21.1)
    47.4 (24.4 to 71.1)
    100 (97.4 to 100)
    23.3 (11.8 to 38.6)
        T3: PMB2001 [A56] - 1:16 (n=68,71,24,19,139,43)
    100 (94.7 to 100)
    100 (94.9 to 100)
    4.2 (0.1 to 21.1)
    42.1 (20.3 to 66.5)
    100 (97.4 to 100)
    20.9 (10 to 36)
        T3: PMB2001 [A56] - 1:32 (n=68,71,24,19,139,43)
    97.1 (89.8 to 99.6)
    100 (94.9 to 100)
    4.2 (0.1 to 21.1)
    21.1 (6.1 to 45.6)
    98.6 (94.9 to 99.8)
    11.6 (3.9 to 25.1)
        T3: PMB2001 [A56] - 1:64 (n=68,71,24,19,139,43)
    92.6 (83.7 to 97.6)
    94.4 (86.2 to 98.4)
    4.2 (0.1 to 21.1)
    5.3 (0.1 to 26)
    93.5 (88.1 to 97)
    4.7 (0.6 to 15.8)
        T3: PMB2001 [A56] - 1:128 (n=68,71,24,19,139,43)
    76.5 (64.6 to 85.9)
    77.5 (66 to 86.5)
    0 (0 to 14.2)
    0 (0 to 17.6)
    77 (69.1 to 83.7)
    0 (0 to 8.2)
        T4: PMB2001 [A56] - 1:4 (n=61,70,24,22,131,46)
    82 (70 to 90.6)
    85.7 (75.3 to 92.9)
    20.8 (7.1 to 42.2)
    22.7 (7.8 to 45.4)
    84 (76.5 to 89.8)
    21.7 (10.9 to 36.4)
        T4: PMB2001 [A56] - 1:16 (n=61,70,24,22,131,46)
    77 (64.5 to 86.8)
    82.9 (72 to 90.8)
    16.7 (4.7 to 37.4)
    22.7 (7.8 to 45.4)
    80.2 (72.3 to 86.6)
    19.6 (9.4 to 33.9)
        T4: PMB2001 [A56] - 1:32 (n=61,70,24,22,131,46)
    59 (45.7 to 71.4)
    71.4 (59.4 to 81.6)
    16.7 (4.7 to 37.4)
    9.1 (1.1 to 29.2)
    65.6 (56.9 to 73.7)
    13 (4.9 to 26.3)
        T4: PMB2001 [A56] - 1:64 (n=61,70,24,22,131,46)
    39.3 (27.1 to 52.7)
    48.6 (36.4 to 60.8)
    8.3 (1 to 27)
    4.5 (0.1 to 22.8)
    44.3 (35.6 to 53.2)
    6.5 (1.4 to 17.9)
        T4: PMB2001 (A56) - 1:128 (n=61,70,24,22,131,46)
    16.4 (8.2 to 28.1)
    21.4 (12.5 to 32.9)
    0 (0 to 14.2)
    0 (0 to 15.4)
    19.1 (12.7 to 26.9)
    0 (0 to 7.7)
        T1: PMB2948 [B24] - 1:4 (n=67,67,26,21,134,47)
    4.5 (0.9 to 12.5)
    9 (3.4 to 18.5)
    3.8 (0.1 to 19.6)
    4.8 (0.1 to 23.8)
    6.7 (3.1 to 12.4)
    4.3 (0.5 to 14.5)
        T1: PMB2948 [B24] - 1:8 (n=67,67,26,21,134,47)
    3 (0.4 to 10.4)
    7.5 (2.5 to 16.6)
    3.8 (0.1 to 19.6)
    4.8 (0.1 to 23.8)
    5.2 (2.1 to 10.5)
    4.3 (0.5 to 14.5)
        T1: PMB2948 [B24] - 1:16 (n=67,67,26,21,134,47)
    3 (0.4 to 10.4)
    6 (1.7 to 14.6)
    3.8 (0.1 to 19.6)
    4.8 (0.1 to 23.8)
    4.5 (1.7 to 9.5)
    4.3 (0.5 to 14.5)
        T1: PMB2948 [B24] - 1:32 (n=67,67,26,21,134,47)
    1.5 (0 to 8)
    4.5 (0.9 to 12.5)
    3.8 (0.1 to 19.6)
    4.8 (0.1 to 23.8)
    3 (0.8 to 7.5)
    4.3 (0.5 to 14.5)
        T1: PMB2948 [B24] - 1:64 (n=67,67,26,21,134,47)
    1.5 (0 to 8)
    1.5 (0 to 8)
    0 (0 to 13.2)
    0 (0 to 16.1)
    1.5 (0.2 to 5.3)
    0 (0 to 7.5)
        T1: PMB2948 [B24] - 1:128 (n=67,67,26,21,134,47)
    1.5 (0 to 8)
    0 (0 to 5.4)
    0 (0 to 13.2)
    0 (0 to 16.1)
    0.7 (0 to 4.1)
    0 (0 to 7.5)
        T2: PMB2948 [B24] - 1:4 (n=65,63,24,21,128,45)
    53.8 (41 to 66.3)
    68.3 (55.3 to 79.4)
    8.3 (1.1 to 27)
    9.5 (1.2 to 30.4)
    60.9 (51.9 to 69.4)
    8.9 (2.5 to 21.2)
        T2: PMB2948 [B24] - 1:16 (n=65,63,24,21,128,45)
    43.1 (30.8 to 56)
    58.7 (45.6 to 71)
    8.3 (1 to 27)
    9.5 (1.2 to 30.4)
    50.8 (41.8 to 59.7)
    8.9 (2.5 to 21.2)
        T2: PMB2948 [B24] - 1:32 (n=65,63,24,21,128,45)
    15.4 (7.6 to 26.5)
    30.2 (19.2 to 43)
    4.2 (0.1 to 21.1)
    4.8 (0.1 to 23.8)
    22.7 (15.7 to 30.9)
    4.4 (0.5 to 15.1)
        T2: PMB2948 [B24] - 1:64 (n=65,63,24,21,128,45)
    3.1 (0.4 to 10.7)
    15.9 (7.9 to 27.3)
    4.2 (0.1 to 21.1)
    4.8 (0.1 to 23.8)
    9.4 (4.9 to 15.8)
    4.4 (0.5 to 15.1)
        T2: PMB2948 [B24] - 1:128 (n=65,63,24,21,128,45)
    1.5 (0 to 8.3)
    7.9 (2.6 to 17.6)
    0 (0 to 14.2)
    0 (0 to 16.1)
    4.7 (1.7 to 9.9)
    0 (0 to 7.9)
        T3: PMB2948 [B24] - 1:4 (n=63,63,26,20,126,46)
    90.5 (80.4 to 96.4)
    95.2 (86.7 to 99)
    11.5 (2.4 to 30.2)
    0 (0 to 16.8)
    92.9 (86.9 to 96.7)
    6.5 (1.4 to 17.9)
        T3: PMB2948 [B24] - 1:16 (n=63,63,26,20,126,46)
    81 (69.1 to 89.8)
    88.9 (78.4 to 95.4)
    7.7 (0.9 to 25.1)
    0 (0 to 16.8)
    84.9 (77.5 to 90.7)
    4.3 (0.5 to 14.8)
        T3: PMB2948 [B24] - 1:32 (n=63,63,26,20,126,46)
    38.1 (26.1 to 51.2)
    55.6 (42.5 to 68.1)
    3.8 (0.1 to 19.6)
    0 (0 to 16.8)
    46.8 (37.9 to 55.9)
    2.2 (0.1 to 11.5)
        T3: PMB2948 [B24] - 1:64 (n=63,63,26,20,126,46)
    9.5 (3.6 to 19.6)
    27 (16.6 to 39.7)
    0 (0 to 13.2)
    0 (0 to 16.8)
    18.3 (11.9 to 26.1)
    0 (0 to 7.7)
        T3: PMB2948 [B24] - 1:128 (n=63,63,26,20,126,46)
    4.8 (1 to 13.3)
    9.5 (3.6 to 19.6)
    0 (0 to 13.2)
    0 (0 to 16.8)
    7.1 (3.3 to 13.1)
    0 (0 to 7.7)
        T4: PMB2948 [B24] - 1:4 (n=65,64,26,21,129,47)
    13.8 (6.5 to 24.7)
    26.6 (16.3 to 39.1)
    0 (0 to 13.2)
    4.8 (0.1 to 23.8)
    20.2 (13.6 to 28.1)
    2.1 (0.1 to 11.3)
        T4: PMB2948 [B24] - 1:16 (n=65,64,26,21,129,47)
    9.2 (3.5 to 19)
    20.3 (11.3 to 32.2)
    0 (0 to 13.2)
    0 (0 to 16.1)
    14.7 (9.1 to 22)
    0 (0 to 7.5)
        T4: PMB2948 [B24] - 1:32 (n=65,64,26,21,129,47)
    6.2 (1.7 to 15)
    12.5 (5.6 to 23.2)
    0 (0 to 13.2)
    0 (0 to 16.1)
    9.3 (4.9 to 15.7)
    0 (0 to 7.5)
        T4: PMB2948 [B24] - 1:64 (n=65,64,26,21,129,47)
    4.6 (1 to 12.9)
    4.7 (1 to 13.1)
    0 (0 to 13.2)
    0 (0 to 16.1)
    4.7 (1.7 to 9.8)
    0 (0 to 7.5)
        T4: PMB2948 [B24] - 1:128 (n=65,64,26,21,129,47)
    3.1 (0.4 to 10.7)
    3.1 (0.4 to 10.8)
    0 (0 to 13.2)
    0 (0 to 16.1)
    3.1 (0.9 to 7.7)
    0 (0 to 7.5)
        T1: PMB2707 [B44] - 1:4 (n=67,71,26,24,138,50)
    0 (0 to 5.4)
    1.4 (0 to 7.6)
    0 (0 to 13.2)
    0 (0 to 14.2)
    0.7 (0 to 4)
    0 (0 to 7.1)
        T1: PMB2707 [B44] - 1:8 (n=67,71,26,24,138,50)
    0 (0 to 5.4)
    0 (0 to 5.1)
    0 (0 to 13.2)
    0 (0 to 14.2)
    0 (0 to 2.6)
    0 (0 to 7.1)
        T1: PMB2707 [B44] - 1:16 (n=67,71,26,24,138,50)
    0 (0 to 5.4)
    0 (0 to 5.1)
    0 (0 to 13.2)
    0 (0 to 14.2)
    0 (0 to 2.6)
    0 (0 to 7.1)
        T1: PMB2707 [B44] - 1:32 (n=67,71,26,24,138,50)
    0 (0 to 5.4)
    0 (0 to 5.1)
    0 (0 to 13.2)
    0 (0 to 14.2)
    0 (0 to 2.6)
    0 (0 to 7.1)
        T1: PMB2707 [B44] - 1:64 (n=67,71,26,24,138,50)
    0 (0 to 5.4)
    0 (0 to 5.1)
    0 (0 to 13.2)
    0 (0 to 14.2)
    0 (0 to 2.6)
    0 (0 to 7.1)
        T1: PMB2707 [B44] - 1:128 (n=67,71,26,24,138,50)
    0 (0 to 5.4)
    0 (0 to 5.1)
    0 (0 to 13.2)
    0 (0 to 14.2)
    0 (0 to 2.6)
    0 (0 to 7.1)
        T2: PMB2707 [B44] - 1:4 (n=63,67,26,24,130,50)
    66.7 (53.7 to 78)
    49.3 (36.8 to 61.8)
    0 (0 to 13.2)
    0 (0 to 14.2)
    57.7 (48.7 to 66.3)
    0 (0 to 7.1)
        T2: PMB2707 [B44] - 1:16 (n=63,67,26,24,130,50)
    55.6 (42.5 to 68.1)
    31.3 (20.6 to 43.8)
    0 (0 to 13.2)
    0 (0 to 14.2)
    43.1 (34.4 to 52)
    0 (0 to 7.1)
        T2: PMB2707 [B44] - 1:32 (n=63,67,26,24,130,50)
    46 (33.4 to 59.1)
    14.9 (7.4 to 25.7)
    0 (0 to 13.2)
    0 (0 to 14.2)
    30 (22.3 to 38.7)
    0 (0 to 7.1)
        T2: PMB2707 [B44] - 1:64(n=63,67,26,24,130,50)
    27 (16.6 to 39.7)
    9 (3.4 to 18.5)
    0 (0 to 13.2)
    0 (0 to 14.2)
    17.7 (11.6 to 25.4)
    0 (0 to 7.1)
        T2: PMB2707 [B44] - 1:128 (n=63,67,26,24,130,50)
    15.9 (7.9 to 27.3)
    4.5 (0.9 to 12.5)
    0 (0 to 13.2)
    0 (0 to 14.2)
    10 (5.4 to 16.5)
    0 (0 to 7.1)
        T3: PMB2707 [B44] - 1:4 (n=65,69,26,24,134,50)
    81.5 (70 to 90.1)
    82.6 (71.6 to 90.7)
    0 (0 to 13.2)
    0 (0 to 14.2)
    82.1 (74.5 to 88.2)
    0 (0 to 7.1)
        T3: PMB2707 [B44] - 1:16 (n=65,69,26,24,134,50)
    80 (68.2 to 88.9)
    75.4 (63.5 to 84.9)
    0 (0 to 13.2)
    0 (0 to 14.2)
    77.6 (69.6 to 84.4)
    0 (0 to 7.1)
        T3: PMB2707 [B44] - 1:32 (n=65,69,26,24,134,50)
    67.7 (54.9 to 78.8)
    63.8 (51.3 to 75)
    0 (0 to 13.2)
    0 (0 to 14.2)
    65.7 (57 to 73.7)
    0 (0 to 7.1)
        T3: PMB2707 [B44] - 1:64 (n=65,69,26,24,134,50)
    55.4 (42.5 to 67.7)
    49.3 (37 to 61.6)
    0 (0 to 13.2)
    0 (0 to 14.2)
    52.2 (43.4 to 60.9)
    0 (0 to 7.1)
        T3: PMB2707 [B44] - 1:128 (n=65,69,26,24,134,50)
    36.9 (25.3 to 49.8)
    30.4 (19.9 to 42.7)
    0 (0 to 13.2)
    0 (0 to 14.2)
    33.6 (25.7 to 42.2)
    0 (0 to 7.1)
        T4: PMB2707 [B44] - 1:4 (n=66,69,26,23,135,49)
    13.6 (6.4 to 24.3)
    13 (6.1 to 23.3)
    0 (0 to 13.2)
    0 (0 to 14.8)
    13.3 (8.1 to 20.3)
    0 (0 to 7.3)
        T4: PMB2707 [B44] - 1:16 (n=66,69,26,23,135,49)
    9.1 (3.4 to 18.7)
    7.2 (2.4 to 16.1)
    0 (0 to 13.2)
    0 (0 to 14.8)
    8.1 (4.1 to 14.1)
    0 (0 to 7.3)
        T4: PMB2707 [B44] - 1:32 (n=66,69,26,23,135,49)
    6.1 (1.7 to 14.8)
    7.2 (2.4 to 16.1)
    0 (0 to 13.2)
    0 (0 to 14.8)
    6.7 (3.1 to 12.3)
    0 (0 to 7.3)
        T4: PMB2707 [B44] - 1:64 (n=66,69,26,23,135,49)
    6.1 (1.7 to 14.8)
    4.3 (0.9 to 12.2)
    0 (0 to 13.2)
    0 (0 to 14.8)
    5.2 (2.1 to 10.4)
    0 (0 to 7.3)
        T4: PMB2707 [B44] - 1:128 (n=66,69,26,23,135,49)
    3 (0.4 to 10.5)
    2.9 (0.4 to 10.1)
    0 (0 to 13.2)
    0 (0 to 14.8)
    3 (0.8 to 7.4)
    0 (0 to 7.3)
    No statistical analyses for this end point

    Secondary: Serum Bactericidal Assay Using Human Complement (hSBA) Geometric Mean Titers (GMTs) for Each of the 4 Primary Test Strains

    		 Close Top of page
    End point title
    		 Serum Bactericidal Assay Using Human Complement (hSBA) Geometric Mean Titers (GMTs) for Each of the 4 Primary Test Strains
    End point description
    Evaluable immunogenicity population included all eligible subjects randomized to study, received scheduled investigational products, had pre and post vaccination blood drawn with valid and determinate assay results and had no important protocol deviation. Here, "n" signifies number of subjects evaluable for the specified categories and "99999" and "-99999" signifies "Not available" (NA) as CI was not estimable due to the lack of variability of geometric means.
    End point type
    Secondary
    End point timeframe
    Before Vaccination 1 (T1), 1 month after Vaccination 2 (T2), 1 month after Vaccination 3 (T3) and 6 months after Vaccination 3 (T4)
    End point values
    		 Group 1 bivalent rLP2086 (>=24 months to <4 years) Group 1 bivalent rLP2086 (>=4 years to <10 years) Group 2 HAV/Saline (>=24 months to <4 years) Group 2 HAV/Saline (>=4 years to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years) Group 2 HAV/Saline (>=24 months to <10 years)
    Number of subjects analysed
    136
    138
    52
    45
    274
    97
    Units: titers
    geometric mean (confidence interval 95%)
        T1: PMB80 [A22] (n=68,66,26,21,134,47)
    8.3 (7.9 to 8.8)
    9.1 (8.3 to 9.9)
    8.2 (7.8 to 8.7)
    9.8 (7.2 to 13.2)
    8.7 (8.3 to 9.1)
    8.9 (7.8 to 10.1)
        T2: PMB80 [A22](n=64,66,24,21,130,45)
    17.4 (14.2 to 21.4)
    23.1 (18.9 to 28.3)
    8 (-99999 to 99999)
    9.4 (7.4 to 12)
    20.1 (17.4 to 23.2)
    8.6 (7.7 to 9.7)
        T3: PMB80 [A22](n=68,67,25,20,135,45)
    33.7 (26.4 to 42.9)
    38.2 (30.6 to 47.6)
    8.7 (7.3 to 10.3)
    8.9 (7.6 to 10.4)
    35.8 (30.5 to 42.2)
    8.8 (7.8 to 9.8)
        T4: PMB80 [A22](n=63,63,26,21,126,47)
    10.9 (9 to 13.1)
    14.2 (11.8 to 17)
    8.4 (7.8 to 9.1)
    9.1 (7.4 to 11.3)
    12.4 (10.9 to 14.2)
    8.7 (7.9 to 9.7)
        T1: PMB2001 [A56](n=67,65,24,23,132,47)
    4.1 (3.9 to 4.3)
    5.8 (4.6 to 7.3)
    4.9 (3.7 to 6.6)
    6.5 (4.3 to 9.8)
    4.9 (4.3 to 5.5)
    5.6 (4.4 to 7.2)
        T2: PMB2001 [A56](n=66,67,21,22,133,43)
    103.8 (84.2 to 127.9)
    90 (71.9 to 112.7)
    5 (3.6 to 7.1)
    6.6 (4.2 to 10.5)
    96.6 (83 to 112.5)
    5.8 (4.4 to 7.6)
        T3: PMB2001 [A56](n=68,71,24,19,139,43)
    175.6 (139.1 to 221.6)
    191 (153.9 to 237.1)
    4.5 (3.5 to 5.7)
    8.6 (5.4 to 13.8)
    183.3 (156.7 to 214.4)
    6 (4.6 to 7.7)
        T4: PMB2001 [A56](n=61,70,24,22,131,46)
    27 (19.7 to 36.9)
    35.7 (26.6 to 47.8)
    6 (4 to 8.9)
    6 (4.2 to 8.7)
    31.3 (25.3 to 38.7)
    6 (4.6 to 7.8)
        T1: PMB2948 [B24] (n=67,67,26,21,134,47)
    4.3 (3.8 to 4.9)
    4.6 (4 to 5.2)
    4.3 (3.7 to 5.1)
    4.4 (3.6 to 5.4)
    4.5 (4.1 to 4.9)
    4.4 (3.9 to 4.9)
        T2: PMB2948 [B24](n=65,63,24,21,128,45)
    9.1 (7 to 11.9)
    13.7 (10.3 to 18.2)
    4.8 (3.7 to 6.2)
    4.9 (3.6 to 6.6)
    11.1 (9.2 to 13.5)
    4.8 (4 to 5.8)
        T3: PMB2948 [B24](n=63,63,26,20,126,46)
    19.1 (14.9 to 24.5)
    26.8 (21.3 to 33.9)
    4.6 (3.8 to 5.6)
    4 (-99999 to 99999)
    22.6 (19.1 to 26.8)
    4.3 (3.9 to 4.8)
        T4: PMB2948 [B24](n=65,64,26,21,129,47)
    5.1 (4.1 to 6.3)
    6.2 (4.9 to 7.7)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    5.6 (4.8 to 6.5)
    4 (-99999 to 99999)
        T1: PMB2707 [B44] (n=67,71,26,24,138,50)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
        T2: PMB2707 [B44](n=63,67,26,24,130,50)
    17.1 (11.8 to 24.8)
    8.2 (6.3 to 10.6)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    11.7 (9.3 to 14.7)
    4 (-99999 to 99999)
        T3: PMB2707 [B44](n=65,69,26,24,134,50)
    43.6 (29.9 to 63.6)
    36.5 (25.2 to 52.7)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    39.8 (30.6 to 51.6)
    4 (-99999 to 99999)
        T4: PMB2707 [B44](n=66,69,26,23,135,49)
    5.2 (4.2 to 6.4)
    5 (4.1 to 6.2)
    4 (-99999 to 99999)
    4 (-99999 to 99999)
    5.1 (4.4 to 5.9)
    4 (-99999 to 99999)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    AEs/SAEs: Recorded from first vaccination through 6 months after third vaccination. Subjects recorded local reactions and systemic events in e-diary within 7 days after first, second and third vaccination.
    Adverse event reporting additional description
    SAEs and AEs were grouped by system organ class and preferred term. AEs included AEs collected in the e-diary (local and systemic reactions; systematic assessment) and AEs collected on the case report form at each visit (nonsystematic assessment).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Group 2 HAV/Saline (>=24 months to <10 years)
    Reporting group description
    		 Subjects from >=24 months to <10 years of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Reporting group title
    Group 1 bivalent rLP2086 (>=24 months to <10 years)
    Reporting group description
    		 Subjects from >=24 months to <10 years of age, received intramuscular injection of rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Serious adverse events
    		 Group 2 HAV/Saline (>=24 months to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 106 (0.94%)
    5 / 294 (1.70%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Skin and subcutaneous tissue disorders
    Rash papular
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Synovitis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Group 2 HAV/Saline (>=24 months to <10 years) Group 1 bivalent rLP2086 (>=24 months to <10 years)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    87 / 106 (82.08%)
    281 / 294 (95.58%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Crying
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Fatigue (Systematic)
    alternative assessment type: Systematic
         subjects affected / exposed
    41 / 106 (38.68%)
    175 / 294 (59.52%)
         occurrences all number
    59
    365
    Fatigue (Non Systematic)
         subjects affected / exposed
    0 / 106 (0.00%)
    3 / 294 (1.02%)
         occurrences all number
    0
    3
    Injection site erythema (redness)
    alternative assessment type: Systematic
         subjects affected / exposed
    18 / 106 (16.98%)
    177 / 294 (60.20%)
         occurrences all number
    26
    328
    Injection site hypersensitivity
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Injection site pain (pain)
    alternative assessment type: Systematic
         subjects affected / exposed
    35 / 106 (33.02%)
    248 / 294 (84.35%)
         occurrences all number
    53
    595
    Injection site pain
         subjects affected / exposed
    1 / 106 (0.94%)
    4 / 294 (1.36%)
         occurrences all number
    1
    4
    Injection site pruritus
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Injection site swelling (swelling)
    alternative assessment type: Systematic
         subjects affected / exposed
    10 / 106 (9.43%)
    137 / 294 (46.60%)
         occurrences all number
    12
    253
    Local swelling
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Pyrexia (fever)
    alternative assessment type: Systematic
         subjects affected / exposed
    13 / 106 (12.26%)
    72 / 294 (24.49%)
         occurrences all number
    16
    102
    Pyrexia
         subjects affected / exposed
    2 / 106 (1.89%)
    16 / 294 (5.44%)
         occurrences all number
    2
    18
    Vaccination site pain
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    2
    Immune system disorders
    Allergy to arthropod bite
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Food allergy
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Seasonal allergy
         subjects affected / exposed
    0 / 106 (0.00%)
    3 / 294 (1.02%)
         occurrences all number
    0
    3
    Reproductive system and breast disorders
    Balanoposthitis
    Additional description: This event is a gender specific event.
         subjects affected / exposed [1]
    1 / 44 (2.27%)
    0 / 148 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Allergic cough
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Tonsillar hypertrophy
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    0 / 106 (0.00%)
    4 / 294 (1.36%)
         occurrences all number
    0
    4
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 106 (0.94%)
    1 / 294 (0.34%)
         occurrences all number
    1
    1
    Concussion
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Corneal abrasion
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Fall
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    2
    Foot fracture
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Foreign body in eye
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Laceration
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Head injury
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    2
    Nasal injury
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Radius fracture
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Limb injury
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache (Systematic)
    alternative assessment type: Systematic
         subjects affected / exposed
    22 / 106 (20.75%)
    98 / 294 (33.33%)
         occurrences all number
    31
    147
    Headache (Non Systematic)
         subjects affected / exposed
    0 / 106 (0.00%)
    6 / 294 (2.04%)
         occurrences all number
    0
    6
    Lethargy
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    2
    Speech disorder
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Tremor
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Middle ear effusion
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Aphthous ulcer
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Cheilitis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    2
    Dental caries
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Diarrhoea (diarrhea)
    alternative assessment type: Systematic
         subjects affected / exposed
    13 / 106 (12.26%)
    51 / 294 (17.35%)
         occurrences all number
    16
    69
    Diarrhoea
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    4
    Inguinal hernia
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Lip swelling
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Teething
         subjects affected / exposed
    2 / 106 (1.89%)
    0 / 294 (0.00%)
         occurrences all number
    2
    0
    Vomiting (Systematic)
    alternative assessment type: Systematic
         subjects affected / exposed
    13 / 106 (12.26%)
    35 / 294 (11.90%)
         occurrences all number
    13
    40
    Vomiting (Non Systematic)
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Rash generalised
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Rash macular
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Rash papular
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    3 / 106 (2.83%)
    1 / 294 (0.34%)
         occurrences all number
    3
    1
    Swelling face
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    2
    Urticaria
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia (joint pain)
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 106 (6.60%)
    43 / 294 (14.63%)
         occurrences all number
    12
    61
    Arthritis
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Myalgia (muscle pain)
    alternative assessment type: Systematic
         subjects affected / exposed
    9 / 106 (8.49%)
    83 / 294 (28.23%)
         occurrences all number
    13
    121
    Myalgia
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Neck mass
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Scoliosis
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Synovitis
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    2
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    6 / 106 (5.66%)
    19 / 294 (6.46%)
         occurrences all number
    7
    25
    Chronic tonsillitis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    2 / 106 (1.89%)
    9 / 294 (3.06%)
         occurrences all number
    2
    9
    Enterobiasis
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Exanthema subitum
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Foot and mouth disease
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 106 (0.00%)
    5 / 294 (1.70%)
         occurrences all number
    0
    5
    Gastroenteritis
         subjects affected / exposed
    10 / 106 (9.43%)
    39 / 294 (13.27%)
         occurrences all number
    10
    47
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 106 (0.94%)
    1 / 294 (0.34%)
         occurrences all number
    1
    1
    Gingivitis
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    2
    0
    Herpes dermatitis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Hordeolum
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Impetigo
         subjects affected / exposed
    0 / 106 (0.00%)
    5 / 294 (1.70%)
         occurrences all number
    0
    5
    Infection parasitic
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Infectious mononucleosis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Laryngitis
         subjects affected / exposed
    7 / 106 (6.60%)
    6 / 294 (2.04%)
         occurrences all number
    7
    7
    Meningitis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    2 / 106 (1.89%)
    5 / 294 (1.70%)
         occurrences all number
    2
    5
    Influenza
         subjects affected / exposed
    2 / 106 (1.89%)
    7 / 294 (2.38%)
         occurrences all number
    2
    7
    Otitis media acute
         subjects affected / exposed
    1 / 106 (0.94%)
    1 / 294 (0.34%)
         occurrences all number
    1
    1
    Otitis media viral
         subjects affected / exposed
    0 / 106 (0.00%)
    2 / 294 (0.68%)
         occurrences all number
    0
    3
    Paronychia
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    9 / 106 (8.49%)
    33 / 294 (11.22%)
         occurrences all number
    11
    50
    Pneumonia bacterial
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    4 / 106 (3.77%)
    3 / 294 (1.02%)
         occurrences all number
    5
    3
    Pyelonephritis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    4 / 106 (3.77%)
    12 / 294 (4.08%)
         occurrences all number
    4
    14
    Otitis media
         subjects affected / exposed
    12 / 106 (11.32%)
    44 / 294 (14.97%)
         occurrences all number
    14
    54
    Rhinitis
         subjects affected / exposed
    2 / 106 (1.89%)
    4 / 294 (1.36%)
         occurrences all number
    2
    4
    Scarlet fever
         subjects affected / exposed
    1 / 106 (0.94%)
    2 / 294 (0.68%)
         occurrences all number
    1
    2
    Sinusitis
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Skin bacterial infection
         subjects affected / exposed
    1 / 106 (0.94%)
    0 / 294 (0.00%)
         occurrences all number
    1
    0
    Tonsillitis
         subjects affected / exposed
    3 / 106 (2.83%)
    10 / 294 (3.40%)
         occurrences all number
    3
    12
    Upper respiratory tract infection
         subjects affected / exposed
    16 / 106 (15.09%)
    59 / 294 (20.07%)
         occurrences all number
    20
    82
    Urinary tract infection
         subjects affected / exposed
    1 / 106 (0.94%)
    5 / 294 (1.70%)
         occurrences all number
    1
    5
    Varicella zoster virus infection
         subjects affected / exposed
    0 / 106 (0.00%)
    1 / 294 (0.34%)
         occurrences all number
    0
    1
    Varicella
         subjects affected / exposed
    4 / 106 (3.77%)
    7 / 294 (2.38%)
         occurrences all number
    4
    7
    Viral upper respiratory tract infection
         subjects affected / exposed
    8 / 106 (7.55%)
    31 / 294 (10.54%)
         occurrences all number
    15
    47
    Vulvitis
    Additional description: This event is a gender specific event.
         subjects affected / exposed [2]
    0 / 62 (0.00%)
    1 / 146 (0.68%)
         occurrences all number
    0
    1
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is a gender specific event.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is a gender specific event.

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 04 12:13:12 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA