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    Clinical Trial Results:
    A Phase 2, randomized,controlled, observer-Blinded study conducted to describe the immunogenicity, safety, and tolerability of a Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein 2086 Vaccine (Bivalent rLP2086) when administered to healthy toddlers Aged 12 to <18 Months or 18 to <24 Months

    Summary
    EudraCT number
    		 2011-004400-38
    Trial protocol
    		 CZ   PL   FI  
    Global end of trial date

    Results information
    Results version number
    		 v3(current)
    This version publication date
    15 Sep 2021
    First version publication date
    09 Mar 2018
    Other versions
    		 v1 , v2
    Version creation reason
    • New data added to full data set
    Secondary Results

    Trial information

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    Trial identification
    Sponsor protocol code
    B1971035
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02534935
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 110017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 18007181021, 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
    Interim
    Date of interim/final analysis
    26 Sep 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Aug 2017
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To describe the immune response as measured by hSBA performed with 4 primary MnB 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 toddlers aged 12 to <18 months and healthy toddlers aged 18 to <24 months at study entry and also 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 events (AEs), serious adverse events (SAEs), newly diagnosed chronic medical conditions (NDCMCs), medically attended events (MAEs), and immediate AEs in healthy toddlers 12 to <18 months and 18 to <24 months of age 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
    31 Aug 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    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
    Australia: 118
    Country: Number of subjects enrolled
    Czech Republic: 100
    Country: Number of subjects enrolled
    Finland: 26
    Country: Number of subjects enrolled
    Poland: 152
    Worldwide total number of subjects
    396
    EEA total number of subjects
    278
    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)
    396
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 396 subjects were enrolled at multiple centers in four countries in the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months)
    Arm description
    		 Subjects from greater than or equal to (>=) 12 months to less than (<) 24 months of age, received intramuscular injection of 60 microgram (µg) of bivalent 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 2: 120-µg bivalent rLP2086 (>=12 months to <24 months)
    Arm description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of 120 µg of bivalent 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 3: HAV/Saline (>=12 months to <24 months)
    Arm description
    		 Subjects from >=12 months to <24 months 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months)
    Started
    44
    220
    132
    Completed
    44
    210
    127
    Not completed
    0
    10
    5
         Consent withdrawn by subject
    -
    3
    3
         Adverse event, non-fatal
    -
    2
    -
         No longer meets the eligibility criteria
    -
    3
    -
         No longer willing to participate
    -
    1
    1
         Lost to follow-up
    -
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months)
    Reporting group description
    		 Subjects from greater than or equal to (>=) 12 months to less than (<) 24 months of age, received intramuscular injection of 60 microgram (µg) of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 3: HAV/Saline (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Reporting group values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Total
    Number of subjects
    		 44 220 132 396
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 44 220 132 396
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 16.9 ( 4.08 ) 17.4 ( 3.54 ) 17.3 ( 3.58 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 21 115 74 210
        Male
    		 23 105 58 186
    Race/Ethnicity, Customized
    Units: Subjects
        Race: White|
    		 37 210 127 374
        Race: Asian|
    		 5 2 1 8
        Race: Other|
    		 2 8 4 14
    Race/Ethnicity, Customized
    Units: Subjects
        Ethinicity: Hispanic|
    		 0 2 0 2
        Ethinicity: Non-Hispanic|
    		 44 218 132 394

    End points

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    End points reporting groups
    Reporting group title
    Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months)
    Reporting group description
    		 Subjects from greater than or equal to (>=) 12 months to less than (<) 24 months of age, received intramuscular injection of 60 microgram (µg) of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 3: HAV/Saline (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months 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: 60-µg bivalent rLP2086 (>=12 months to <18 months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects from >=12 months to <18 months of age, received intramuscular injection of 60 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects from >=18 months to <24 months of age, received intramuscular injection of 60 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects from >=12 months to <18 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects from >=18 months to <24 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 3: HAV/Saline (>=12 months to <18 months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects from >=12 months to <18 months of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Subject analysis set title
    Group 3: HAV/Saline (>=18 months to <24 months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects from >=18 months to <24 months 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: 60-µg bivalent rLP2086 (>=12 months to <18 months)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects from >=12 months to <18 months of age, received intramuscular injection of 60 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects from >=18 months to <24 months of age, received intramuscular injection of 60 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects from >=12 months to <18 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects from >=18 months to <24 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Subject analysis set title
    Group 3: HAV/Saline (>=12 months to <18 months)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects from >=12 months to <18 months of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Subject analysis set title
    Group 3: HAV/Saline (>=18 months to <24 months)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects from >=18 months to <24 months of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Primary: Percentage of Subjects With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Neisseria Meningitidis Serogroup B (MnB) Test Strains 1 Month After Vaccination 3

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    End point title
    		 Percentage of Subjects With Serum Bactericidal Assay Using Human Complement (hSBA) Titers >= Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Neisseria Meningitidis Serogroup B (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). 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,Overall number of subjects analyzed(N) signifies subjects evaluable for this endpoint and n signifies number of subjects analyzed at specific time points only.
    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: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    9
    11
    47
    51
    31
    30
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 [A22]| (n =9, 11, 45, 51, 31, 29)
    88.9 (51.8 to 99.7)
    90.9 (58.7 to 99.8)
    91.1 (78.8 to 97.5)
    88.2 (76.1 to 95.6)
    3.2 (0.1 to 16.7)
    6.9 (0.8 to 22.8)
        PMB2001 [A56]| (n =9, 10, 47, 48, 24, 30)
    100.0 (66.4 to 100.0)
    100.0 (69.2 to 100.0)
    100.0 (92.5 to 100.0)
    100.0 (92.6 to 100.0)
    0.0 (0.0 to 14.2)
    3.3 (0.1 to 17.2)
        PMB2948 [B24]| (n =9, 11, 45, 50, 31, 29)
    88.9 (51.8 to 99.7)
    81.8 (48.2 to 97.7)
    71.1 (55.7 to 83.6)
    72.0 (57.5 to 83.8)
    3.2 (0.1 to 16.7)
    6.9 (0.8 to 22.8)
        PMB2707 [B44]| (n =9, 10, 47, 47, 24, 30)
    88.9 (51.8 to 99.7)
    90.0 (55.5 to 99.7)
    87.2 (74.3 to 95.2)
    85.1 (71.7 to 93.8)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 1 [2]
    End point description
    Local reactions included tenderness at injection site, swelling and redness collected by using an e-diary. Tenderness was graded as: mild (hurted if gently touched), moderate (hurted if gently touched with crying) and severe (caused limitation of limb movement). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). Safety population: all subjects who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available.
    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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [3]
    220 [4]
    132 [5]
    22 [6]
    22 [7]
    110 [8]
    110 [9]
    66 [10]
    66 [11]
    Units: percentage of subjects
    number (confidence interval 95%)
        Tenderness at injection site: Any|
    59.1 (43.2 to 73.7)
    57.7 (50.9 to 64.3)
    17.4 (11.4 to 25.0)
    68.2 (45.1 to 86.1)
    50.0 (28.2 to 71.8)
    50.9 (41.2 to 60.6)
    64.5 (54.9 to 73.4)
    15.2 (7.5 to 26.1)
    19.7 (10.9 to 31.3)
        Tenderness at injection site: Mild|
    36.4 (22.4 to 52.2)
    30.9 (24.9 to 37.5)
    15.9 (10.1 to 23.3)
    45.5 (24.4 to 67.8)
    27.3 (10.7 to 50.2)
    27.3 (19.2 to 36.6)
    34.5 (25.7 to 44.2)
    12.1 (5.4 to 22.5)
    19.7 (10.9 to 31.3)
        Tenderness at injection site: Moderate|
    20.5 (9.8 to 35.3)
    22.7 (17.4 to 28.8)
    1.5 (0.2 to 5.4)
    22.7 (7.8 to 45.4)
    18.2 (5.2 to 40.3)
    20.9 (13.7 to 29.7)
    24.5 (16.8 to 33.7)
    3.0 (0.4 to 10.5)
    0.0 (0.0 to 5.4)
        Tenderness at injection site: Severe|
    2.3 (0.1 to 12.0)
    4.1 (1.9 to 7.6)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    4.5 (0.1 to 22.8)
    2.7 (0.6 to 7.8)
    5.5 (2.0 to 11.5)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        Redness: Any|
    54.5 (38.8 to 69.6)
    46.8 (40.1 to 53.6)
    15.2 (9.5 to 22.4)
    68.2 (45.1 to 86.1)
    40.9 (20.7 to 63.6)
    50.9 (41.2 to 60.6)
    42.7 (33.3 to 52.5)
    13.6 (6.4 to 24.3)
    16.7 (8.6 to 27.9)
        Redness: Mild|
    34.1 (20.5 to 49.9)
    28.6 (22.8 to 35.1)
    15.2 (9.5 to 22.4)
    40.9 (20.7 to 63.6)
    27.3 (10.7 to 50.2)
    35.5 (26.6 to 45.1)
    21.8 (14.5 to 30.7)
    13.6 (6.4 to 24.3)
    16.7 (8.6 to 27.9)
        Redness: Moderate|
    20.5 (9.8 to 35.3)
    16.8 (12.1 to 22.4)
    0.0 (0.0 to 2.8)
    27.3 (10.7 to 50.2)
    13.6 (2.9 to 34.9)
    14.5 (8.5 to 22.5)
    19.1 (12.2 to 27.7)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        Redness: Severe|
    0.0 (0.0 to 8.0)
    1.4 (0.3 to 3.9)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.9 (0.0 to 5.0)
    1.8 (0.2 to 6.4)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        Swelling: Any|
    29.5 (16.8 to 45.2)
    28.6 (22.8 to 35.1)
    9.8 (5.3 to 16.3)
    36.4 (17.2 to 59.3)
    22.7 (7.8 to 45.4)
    30.0 (21.6 to 39.5)
    27.3 (19.2 to 36.6)
    7.6 (2.5 to 16.8)
    12.1 (5.4 to 22.5)
        Swelling: Mild|
    18.2 (8.2 to 32.7)
    17.3 (12.5 to 22.9)
    9.8 (5.3 to 16.3)
    22.7 (7.8 to 45.4)
    13.6 (2.9 to 34.9)
    15.5 (9.3 to 23.6)
    19.1 (12.2 to 27.7)
    7.6 (2.5 to 16.8)
    12.1 (5.4 to 22.5)
        Swelling: Moderate|
    11.4 (3.8 to 24.6)
    10.9 (7.1 to 15.8)
    0.0 (0.0 to 2.8)
    13.6 (2.9 to 34.9)
    9.1 (1.1 to 29.2)
    13.6 (7.8 to 21.5)
    8.2 (3.8 to 15.0)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        Swelling: Severe|
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.5)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.9 (0.0 to 5.0)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
    Notes
    [3] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [4] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [5] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [6] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [7] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [8] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [9] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [10] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [11] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 2 [12]
    End point description
    Local reactions included tenderness at injection site, swelling and redness collected by using an e-diary. Tenderness was graded as: mild (hurted if gently touched), moderate (hurted if gently touched with crying) and severe (caused limitation of limb movement). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). Safety population: all subjects who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N (number of subjects analyzed) signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    within 7 Days after Vaccination 2
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [13]
    212 [14]
    128 [15]
    22 [16]
    22 [17]
    105 [18]
    107 [19]
    63 [20]
    65 [21]
    Units: percentage of subjects
    number (confidence interval 95%)
        Tenderness at injection site: Any|
    47.7 (32.5 to 63.3)
    53.3 (46.3 to 60.2)
    14.8 (9.2 to 22.2)
    45.5 (24.4 to 67.8)
    50.0 (28.2 to 71.8)
    45.7 (36.0 to 55.7)
    60.7 (50.8 to 70.0)
    14.3 (6.7 to 25.4)
    15.4 (7.6 to 26.5)
        Tenderness at injection site: Mild|
    36.4 (22.4 to 52.2)
    32.1 (25.8 to 38.8)
    14.1 (8.6 to 21.3)
    31.8 (13.9 to 54.9)
    40.9 (20.7 to 63.6)
    31.4 (22.7 to 41.2)
    32.7 (24.0 to 42.5)
    12.7 (5.6 to 23.5)
    15.4 (7.6 to 26.5)
        Tenderness at injection site: Moderate|
    11.4 (3.8 to 24.6)
    18.4 (13.4 to 24.3)
    0.8 (0.0 to 4.3)
    13.6 (2.9 to 34.9)
    9.1 (1.1 to 29.2)
    12.4 (6.8 to 20.0)
    22.5 (16.5 to 24.3)
    1.6 (0.0 to 8.5)
    0.0 (0.0 to 5.5)
        Tenderness at injection site: Severe|
    0.0 (0.0 to 8.0)
    2.8 (1.0 to 6.1)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.9 (0.2 to 6.7)
    3.7 (1.0 to 9.3)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Redness: Any|
    40.9 (26.3 to 56.8)
    35.8 (29.4 to 42.7)
    7.8 (3.8 to 13.9)
    50.0 (28.2 to 71.8)
    31.8 (13.9 to 54.9)
    33.3 (24.4 to 43.2)
    38.3 (29.1 to 48.2)
    6.3 (1.8 to 15.5)
    9.2 (3.5 to 19.0)
        Redness: Mild|
    34.1 (20.5 to 49.9)
    22.6 (17.2 to 28.9)
    7.8 (3.8 to 13.9)
    40.9 (20.7 to 63.6)
    27.3 (10.7 to 50.2)
    21.9 (14.4 to 31.0)
    23.4 (15.7 to 32.5)
    6.3 (1.8 to 15.5)
    9.2 (3.5 to 19.0)
        Redness: Moderate|
    6.8 (1.4 to 18.7)
    13.2 (9.0 to 18.5)
    0.0 (0.0 to 2.8)
    9.1 (1.1 to 29.2)
    4.5 (0.1 to 22.8)
    11.4 (6.0 to 19.1)
    15.0 (8.8 to 23.1)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Redness: Severe|
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Swelling: Any|
    22.7 (11.5 to 37.8)
    20.3 (15.1 to 26.3)
    4.7 (1.7 to 9.9)
    18.2 (5.2 to 40.3)
    27.3 (10.7 to 50.2)
    21.0 (13.6 to 30.0)
    19.6 (12.6 to 28.4)
    1.6 (0.0 to 8.5)
    7.7 (2.5 to 17.0)
        Swelling: Mild|
    15.9 (6.6 to 30.1)
    13.7 (9.4 to 19.1)
    4.7 (1.7 to 9.9)
    18.2 (5.2 to 40.3)
    13.6 (2.9 to 34.9)
    14.3 (8.2 to 22.5)
    13.1 (7.3 to 21.0)
    1.6 (0.0 to 8.5)
    7.7 (2.5 to 17.0)
        Swelling: Moderate|
    6.8 (1.4 to 18.7)
    6.1 (3.3 to 10.3)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    13.6 (2.9 to 34.9)
    6.7 (2.7 to 13.3)
    5.6 (2.1 to 11.8)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Swelling: Severe|
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.6)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.9 (0.0 to 5.1)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
    Notes
    [13] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [14] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [15] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [16] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [17] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [18] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [19] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [20] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [21] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Subjects Reporting Pre-specified Local Reactions Within 7 Days After Vaccination 3 [22]
    End point description
    Local reactions included tenderness at injection site, swelling and redness collected by using an e-diary. Tenderness was graded as: mild (hurted if gently touched), moderate (hurted if gently touched with crying) and severe (caused limitation of limb movement). Redness and swelling were graded as: mild (0.5-2.0 cm), moderate (2.5 to 7.0 cm) and severe (>7.0 cm). Safety population: all subjects who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    within 7 Days after Vaccination 3
    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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [23]
    212 [24]
    128 [25]
    22 [26]
    22 [27]
    104 [28]
    108 [29]
    65 [30]
    63 [31]
    Units: percentage of subjects
    number (confidence interval 95%)
        Tenderness at injection site: Any|
    56.8 (41.0 to 71.7)
    57.1 (50.1 to 63.8)
    15.6 (9.8 to 23.1)
    54.5 (32.2 to 75.6)
    59.1 (36.4 to 79.3)
    51.9 (41.9 to 61.8)
    62.0 (52.2 to 71.2)
    16.9 (8.8 to 28.3)
    14.3 (6.7 to 25.4)
        Tenderness at injection site: Mild|
    31.8 (18.6 to 47.6)
    32.1 (25.8 to 38.8)
    12.5 (7.3 to 19.5)
    22.7 (7.8 to 45.4)
    40.9 (20.7 to 63.6)
    29.8 (21.2 to 39.6)
    34.3 (25.4 to 44)
    12.3 (5.5 to 22.8)
    12.7 (5.6 to 23.5)
        Tenderness at injection site: Moderate|
    25.0 (13.2 to 40.3)
    19.8 (14.7 to 25.8)
    3.1 (0.9 to 7.8)
    31.8 (13.9 to 54.9)
    18.2 (5.2 to 40.3)
    17.3 (10.6 to 26.0)
    22.2 (14.8 to 31.2)
    4.6 (1.0 to 12.9)
    1.6 (0.0 to 8.5)
        Tenderness at injection site: Severe|
    0.0 (0.0 to 8.0)
    5.2 (2.6 to 9.1)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    4.8 (1.6 to 10.9)
    5.6 (2.1 to 11.7)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.7)
        Redness: Any|
    38.6 (24.4 to 54.5)
    33.0 (26.7 to 39.8)
    7.8 (3.8 to 13.9)
    40.9 (20.7 to 63.6)
    36.4 (17.2 to 59.3)
    32.7 (23.8 to 42.6)
    33.3 (24.6 to 43.1)
    7.7 (2.5 to 17.0)
    7.9 (2.6 to 17.6)
        Redness: Mild|
    29.5 (16.8 to 45.2)
    20.8 (15.5 to 26.8)
    7.0 (3.3 to 12.9)
    31.8 (13.9 to 54.9)
    27.3 (10.7 to 50.2)
    23.1 (15.4 to 32.4)
    18.5 (11.7 to 27.1)
    6.2 (1.7 to 15.0)
    7.9 (2.6 to 17.6)
        Redness: Moderate|
    9.1 (2.5 to 21.7)
    11.8 (7.8 to 16.9)
    0.8 (0.0 to 4.3)
    9.1 (1.1 to 29.2)
    9.1 (1.1 to 29.2)
    8.7 (4.0 to 15.8)
    14.8 (8.7 to 22.9)
    1.5 (0.0 to 8.3)
    0.0 (0.0 to 5.7)
        Redness: Severe|
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.6)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.0 (0.0 to 5.2)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.7)
        Swelling: Any|
    22.7 (11.5 to 37.8)
    22.6 (17.2 to 28.9)
    5.5 (2.2 to 10.9)
    18.2 (5.2 to 40.3)
    27.3 (10.7 to 50.2)
    23.1 (15.4 to 32.4)
    22.2 (14.8 to 31.2)
    4.6 (1.0 to 12.9)
    6.3 (1.8 to 15.5)
        Swelling: Mild|
    11.4 (3.8 to 24.6)
    13.7 (9.4 to 19.1)
    4.7 (1.7 to 9.9)
    9.1 (1.1 to 29.2)
    13.6 (2.9 to 34.9)
    16.3 (9.8 to 24.9)
    11.1 (5.9 to 18.6)
    4.6 (1.0 to 12.9)
    4.8 (1.0 to 13.3)
        Swelling: Moderate|
    11.4 (3.8 to 24.6)
    8.5 (5.1 to 13.1)
    0.8 (0.0 to 4.3)
    9.1 (1.1 to 29.2)
    13.6 (2.9 to 34.9)
    5.8 (2.1 to 12.1)
    11.1 (5.9 to 18.6)
    0.0 (0.0 to 5.5)
    1.6 (0.0 to 8.5)
        Swelling: Severe|
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.6)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.0 (0.0 to 5.2)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.7)
    Notes
    [23] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [24] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [25] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [26] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [27] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [28] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [29] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [30] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [31] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 1 [32]
    End point description
    Systemic reactions included fever, irritability, drowsiness, loss of or decreased appetite 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. Irritability was graded as mild (easily consolable), moderate (requiring increased attention) and severe (inconsolable). Drowsiness was graded as mild (Increased or prolonged sleeping bouts), moderate (slightly subdued interfering with daily activity) and severe (disabling not interested in usual daily activity). Loss of or decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Safety population: all subjects who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available.
    End point type
    Primary
    End point timeframe
    within 7 Days after Vaccination 1
    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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [33]
    220 [34]
    132 [35]
    22 [36]
    22 [37]
    110 [38]
    110 [39]
    66 [40]
    66 [41]
    Units: percentage of subjects
    number (confidence interval 95%)
        Fever >=38 degrees C|
    36.4 (22.4 to 52.2)
    27.7 (21.9 to 34.1)
    6.1 (2.7 to 11.6)
    40.9 (20.7 to 63.6)
    31.8 (13.9 to 54.9)
    28.2 (20.0 to 37.6)
    27.3 (19.2 to 36.6)
    10.6 (4.4 to 20.6)
    1.5 (0.0 to 8.2)
        Fever 38 to <38.5 degrees C|
    20.5 (9.8 to 35.3)
    7.3 (4.2 to 11.5)
    3.8 (1.2 to 8.6)
    22.7 (7.8 to 45.4)
    18.2 (5.2 to 40.3)
    7.3 (3.2 to 13.8)
    7.3 (3.2 to 13.8)
    6.1 (1.7 to 14.8)
    1.5 (0.0 to 8.2)
        Fever 38.5 to <39 degrees C|
    11.4 (3.8 to 24.6)
    14.1 (9.8 to 19.4)
    0.8 (0.0 to 4.1)
    13.6 (2.9 to 34.9)
    9.1 (1.1 to 29.2)
    14.5 (8.5 to 22.5)
    13.6 (7.8 to 21.5)
    1.5 (0.0 to 8.2)
    0.0 (0.0 to 5.4)
        Fever 39 to <39.5 degrees C|
    0.0 (0.0 to 8.0)
    4.1 (1.9 to 7.6)
    1.5 (0.2 to 5.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    4.5 (1.5 to 10.3)
    3.6 (1.0 to 9.0)
    3.0 (0.4 to 10.5)
    0.0 (0.0 to 5.4)
        Fever 39.5 to <=40 degrees C|
    4.5 (0.6 to 15.5)
    1.8 (0.5 to 4.6)
    0.0 (0.0 to 2.8)
    4.5 (0.1 to 22.8)
    4.5 (0.1 to 22.8)
    1.8 (0.2 to 6.4)
    1.8 (0.2 to 6.4)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        Fever >40 degrees C|
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.5)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.3)
    0.9 (0.0 to 5.0)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        Irritability: Any|
    56.8 (41.0 to 71.7)
    66.4 (59.7 to 72.6)
    37.1 (28.9 to 46.0)
    63.6 (40.7 to 82.8)
    50.0 (28.2 to 71.8)
    71.8 (62.4 to 80.0)
    60.9 (51.1 to 70.1)
    40.9 (29.0 to 53.7)
    33.3 (22.2 to 46.0)
        Irritability: Mild|
    18.2 (8.2 to 32.7)
    17.7 (12.9 to 23.4)
    12.1 (7.1 to 18.9)
    27.3 (10.7 to 50.2)
    9.1 (1.1 to 29.2)
    19.1 (12.2 to 27.7)
    16.4 (10.0 to 24.6)
    10.6 (4.4 to 20.6)
    13.6 (6.4 to 24.3)
        Irritability: Moderate|
    36.4 (22.4 to 52.2)
    42.7 (36.1 to 49.6)
    23.5 (16.5 to 31.6)
    31.8 (13.9 to 54.9)
    40.9 (20.7 to 63.6)
    46.4 (36.8 to 56.1)
    39.1 (29.9 to 48.9)
    30.3 (19.6 to 42.9)
    16.7 (8.6 to 27.9)
        Irritability: Severe|
    2.3 (0.1 to 12.0)
    5.9 (3.2 to 9.9)
    1.5 (0.2 to 5.4)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 15.4)
    6.4 (2.6 to 12.7)
    5.5 (2.0 to 11.5)
    0.0 (0.0 to 5.4)
    3.0 (0.4 to 10.5)
        Drowsiness: Any|
    43.2 (28.3 to 59.0)
    44.1 (37.4 to 50.9)
    18.2 (12.0 to 25.8)
    45.5 (24.4 to 67.8)
    40.9 (20.7 to 63.6)
    45.5 (35.9 to 55.2)
    42.7 (33.3 to 52.5)
    25.8 (15.8 to 38.0)
    10.6 (4.4 to 20.6)
        Drowsiness: Mild|
    34.1 (20.5 to 49.9)
    26.4 (20.7 to 32.7)
    11.4 (6.5 to 18.0)
    36.4 (17.2 to 59.3)
    31.8 (13.9 to 54.9)
    28.2 (20.0 to 37.6)
    24.5 (16.8 to 33.7)
    16.7 (8.6 to 27.9)
    6.1 (1.7 to 14.8)
        Drowsiness: Moderate|
    9.1 (2.5 to 21.7)
    13.6 (9.4 to 18.9)
    6.1 (2.7 to 11.6)
    9.1 (1.1 to 29.2)
    9.1 (1.1 to 29.2)
    11.8 (6.4 to 19.4)
    15.5 (9.3 to 23.6)
    7.6 (2.5 to 16.8)
    4.5 (0.9 to 12.7)
        Drowsiness: Severe|
    0.0 (0.0 to 8.0)
    4.1 (1.9 to 7.6)
    0.8 (0.0 to 4.1)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    5.5 (2.0 to 11.5)
    2.7 (0.6 to 7.8)
    1.5 (0.0 to 8.2)
    0.0 (0.0 to 15.4)
        Loss of or decrease appetite: Any|
    36.4 (22.4 to 52.2)
    45.5 (38.7 to 52.3)
    22.7 (15.9 to 30.8)
    36.4 (17.2 to 59.3)
    36.4 (17.2 to 59.3)
    44.5 (35.1 to 54.3)
    46.4 (36.8 to 56.1)
    34.8 (23.5 to 47.6)
    10.6 (4.4 to 20.6)
        Loss of or decrease appetite: Mild|
    20.5 (9.8 to 35.3)
    20.5 (15.3 to 26.4)
    10.6 (5.9 to 17.2)
    22.7 (7.8 to 45.4)
    18.2 (5.2 to 40.3)
    16.4 (10.0 to 24.6)
    24.5 (16.8 to 33.7)
    13.6 (6.4 to 24.3)
    7.6 (2.5 to 16.8)
        Loss of or decrease appetite: Moderate|
    11.4 (3.8 to 24.6)
    20.0 (14.9 to 25.9)
    9.8 (5.3 to 16.3)
    13.6 (2.9 to 34.9)
    9.1 (1.1 to 29.2)
    25.5 (17.6 to 34.6)
    14.5 (8.5 to 22.5)
    18.2 (9.8 to 29.6)
    1.5 (0.0 to 8.2)
        Loss of or decrease appetite: Severe|
    4.5 (0.6 to 15.5)
    5.0 (2.5 to 8.8)
    2.3 (0.5 to 6.5)
    0.0 (0.0 to 15.4)
    9.1 (1.1 to 29.2)
    2.7 (0.6 to 7.8)
    7.3 (3.2 to 13.8)
    3.0 (0.4 to 10.5)
    1.5 (0.0 to 8.2)
        Antipyretic medication use|
    52.3 (36.7 to 67.5)
    46.8 (40.1 to 53.6)
    19.7 (13.3 to 27.5)
    45.5 (24.4 to 67.8)
    59.1 (36.4 to 79.3)
    52.7 (43.0 to 62.3)
    40.9 (31.6 to 50.7)
    24.2 (14.5 to 36.4)
    15.2 (7.5 to 26.1)
    Notes
    [33] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [34] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [35] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [36] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [37] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [38] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [39] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [40] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [41] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 2 [42]
    End point description
    Systemic reactions included fever, irritability, drowsiness, loss of or decreased appetite 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. Irritability was graded as mild (easily consolable), moderate (requiring increased attention) and severe (inconsolable). Drowsiness was graded as mild (Increased or prolonged sleeping bouts), moderate (slightly subdued interfering with daily activity) and severe (disabling not interested in usual daily activity). Loss of or decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Safety population: all subjects who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    within 7 Days after Vaccination 2
    Notes
    [42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [43]
    212 [44]
    128 [45]
    22 [46]
    22 [47]
    105 [48]
    107 [49]
    63 [50]
    65 [51]
    Units: percentage of subejcts
    number (confidence interval 95%)
        Fever >=38 degrees C|
    11.4 (3.8 to 24.6)
    14.2 (9.8 to 19.6)
    4.7 (1.7 to 9.9)
    13.6 (2.9 to 34.9)
    9.1 (1.1 to 29.2)
    14.3 (8.2 to 22.5)
    14.0 (8.1 to 22.1)
    6.3 (1.8 to 15.5)
    3.1 (0.4 to 10.7)
        Fever 38 to <38.5 degrees C|
    6.8 (1.4 to 18.7)
    6.6 (3.7 to 10.8)
    3.9 (1.3 to 8.9)
    13.6 (2.9 to 34.9)
    0.0 (0.0 to 15.4)
    4.8 (1.6 to 10.8)
    8.4 (3.9 to 15.4)
    4.8 (1.0 to 13.3)
    3.1 (0.4 to 10.7)
        Fever 38.5 to <39 degrees C|
    2.3 (0.1 to 12.0)
    4.7 (2.3 to 8.5)
    0.8 (0.0 to 4.3)
    0.0 (0.0 to 15.4)
    4.5 (0.1 to 22.8)
    6.7 (2.7 to 13.3)
    2.8 (0.6 to 8.0)
    1.6 (0.0 to 8.5)
    0.0 (0.0 to 5.5)
        Fever 39 to <39.5 degrees C|
    0.0 (0.0 to 8.0)
    1.9 (0.5 to 4.8)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.9 (0.2 to 6.7)
    1.9 (0.2 to 6.6)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Fever 39.5 to <=40 degrees C|
    2.3 (0.1 to 12.0)
    0.9 (0.1 to 3.4)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    4.5 (0.1 to 22.8)
    1.0 (0.0 to 5.2)
    0.9 (0.0 to 5.1)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Fever >40 degrees C|
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.7)
    0.0 (0.0 to 5.5)
        Irritability: Any|
    45.5 (30.4 to 61.2)
    54.7 (47.8 to 61.5)
    25.0 (17.8 to 33.4)
    50.0 (28.2 to 71.8)
    40.9 (20.7 to 63.6)
    54.3 (44.3 to 64.0)
    55.1 (45.2 to 64.8)
    31.7 (20.6 to 44.7)
    18.5 (9.9 to 30.0)
        Irritability: Mild|
    29.5 (16.8 to 45.2)
    18.9 (13.8 to 24.8)
    7.0 (3.3 to 12.9)
    40.9 (20.7 to 63.6)
    18.2 (5.2 to 40.3)
    19.0 (12.0 to 27.9)
    18.7 (11.8 to 27.4)
    7.9 (2.6 to 17.6)
    6.2 (1.7 to 15.0)
        Irritability: Moderate|
    13.6 (5.2 to 27.4)
    33.0 (26.7 to 39.8)
    15.6 (9.8 to 23.1)
    4.5 (0.1 to 22.8)
    22.7 (7.8 to 45.4)
    31.4 (22.7 to 41.2)
    34.6 (25.6 to 44.4)
    22.2 (12.7 to 34.5)
    9.2 (3.5 to 19.0)
        Irritability: Severe|
    2.3 (0.1 to 12.0)
    2.8 (1.0 to 6.1)
    2.3 (0.5 to 6.7)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 15.4)
    3.8 (1.0 to 9.5)
    1.9 (0.2 to 6.6)
    1.6 (0.0 to 8.5)
    3.1 (0.4 to 10.7)
        Drowsiness: Any|
    15.9 (6.6 to 30.1)
    30.7 (24.5 to 37.3)
    11.7 (6.7 to 18.6)
    13.6 (2.9 to 34.9)
    18.2 (5.2 to 40.3)
    37.1 (27.9 to 47.1)
    24.3 (16.5 to 33.5)
    19.0 (10.2 to 30.9)
    4.6 (1.0 to 12.9)
        Drowsiness: Mild|
    13.6 (5.2 to 27.4)
    18.4 (13.4 to 24.3)
    7.0 (3.3 to 12.9)
    9.1 (1.1 to 29.2)
    18.2 (5.2 to 40.3)
    22.9 (15.2 to 32.1)
    14.0 (8.1 to 22.1)
    9.5 (3.6 to 19.6)
    4.6 (1.0 to 12.9)
        Drowsiness: Moderate|
    2.3 (0.1 to 12.0)
    10.8 (7.0 to 15.8)
    3.9 (1.3 to 8.9)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 15.4)
    13.3 (7.5 to 21.4)
    8.4 (3.9 to 15.4)
    7.9 (2.6 to 17.6)
    0.0 (0.0 to 5.5)
        Drowsiness: Severe|
    0.0 (0.0 to 8.0)
    1.4 (0.3 to 4.1)
    0.8 (0.0 to 4.3)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.0 (0.0 to 5.2)
    1.9 (0.2 to 6.6)
    1.6 (0.0 to 8.5)
    0.0 (0.0 to 5.5)
        Loss of or decreased appetite: Any|
    25.0 (13.2 to 40.3)
    36.3 (29.8 to 43.2)
    18.0 (11.7 to 25.7)
    31.8 (13.9 to 54.9)
    18.2 (5.2 to 40.3)
    41.0 (31.5 to 51.0)
    31.8 (23.1 to 41.5)
    22.2 (12.7 to 34.5)
    13.8 (6.5 to 24.7)
        Loss of or decreased appetite: Mild|
    22.7 (11.5 to 37.8)
    19.3 (14.3 to 25.3)
    9.4 (4.9 to 15.8)
    27.3 (10.7 to 50.2)
    18.2 (5.2 to 40.3)
    19.0 (12.0 to 27.9)
    19.6 (12.6 to 28.4)
    11.1 (4.6 to 21.6)
    7.7 (2.5 to 17.0)
        Loss of or decreased appetite: Moderate|
    2.3 (0.1 to 12.0)
    12.3 (8.2 to 17.5)
    7.8 (3.8 to 13.9)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 15.4)
    17.1 (10.5 to 25.7)
    7.5 (3.3 to 14.2)
    9.5 (3.6 to 19.6)
    6.2 (1.7 to 15.0)
        Loss of or decreased appetite: Severe|
    0.0 (0.0 to 8.0)
    4.7 (2.3 to 8.5)
    0.8 (0.0 to 4.3)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    4.8 (1.6 to 10.8)
    4.7 (1.5 to 10.6)
    1.6 (0.0 to 8.5)
    0.0 (0.0 to 5.5)
        Antipyretic medication use|
    36.4 (22.4 to 52.2)
    33.5 (27.2 to 40.3)
    14.8 (9.2 to 22.2)
    45.5 (24.4 to 67.8)
    27.3 (10.7 to 50.2)
    35.2 (26.2 to 45.2)
    31.8 (23.1 to 41.5)
    19.0 (10.2 to 30.9)
    10.8 (4.4 to 20.9)
    Notes
    [43] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [44] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [45] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [46] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [47] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [48] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [49] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [50] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [51] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    No statistical analyses for this end point

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

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    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Vaccination 3 [52]
    End point description
    Systemic reactions included fever, irritability, drowsiness, loss of or decreased appetite 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. Irritability was graded as mild (easily consolable), moderate (requiring increased attention) and severe (inconsolable). Drowsiness was graded as mild (Increased or prolonged sleeping bouts), moderate (slightly subdued interfering with daily activity) and severe (disabling not interested in usual daily activity). Loss of or decreased appetite was graded as mild (decreased interest in eating), moderate (decreased oral intake) and severe (refusal to feed). Safety population: all subjects who received at least 1 dose of an investigational product (rLP2086 or HAV vaccine) and had safety data available. Here, N signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    within 7 Days after Vaccination 3
    Notes
    [52] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [53]
    212 [54]
    128 [55]
    22 [56]
    22 [57]
    104 [58]
    108 [59]
    65 [60]
    63 [61]
    Units: percentage of subjects
    number (confidence interval 95%)
        Fever >=38 degrees C|
    4.5 (0.6 to 15.5)
    12.7 (8.6 to 18.0)
    6.3 (2.7 to 11.9)
    4.5 (0.1 to 22.8)
    4.5 (0.1 to 22.8)
    10.6 (5.4 to 18.1)
    14.8 (8.7 to 22.9)
    4.6 (1.0 to 12.9)
    7.9 (2.6 to 17.6)
        Fever 38 to <38.5 degrees C|
    4.5 (0.6 to 15.5)
    6.6 (3.7 to 10.8)
    3.9 (1.3 to 8.9)
    4.5 (0.1 to 22.8)
    4.5 (0.1 to 22.8)
    6.7 (2.7 to 13.4)
    6.5 (2.6 to 12.9)
    3.1 (0.4 to 10.7)
    4.8 (1.0 to 13.3)
        Fever 38.5 to <39 degrees C|
    0.0 (0.0 to 8.0)
    2.4 (0.8 to 5.4)
    1.6 (0.2 to 5.5)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    2.9 (0.6 to 8.2)
    1.9 (0.2 to 6.5)
    1.5 (0.0 to 8.3)
    1.6 (0.0 to 8.5)
        Fever 39 to <39.5 degrees C|
    0.0 (0.0 to 8.0)
    2.4 (0.8 to 5.4)
    0.8 (0.0 to 4.3)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.0 (0.0 to 5.2)
    3.7 (1.0 to 9.2)
    0.0 (0.0 to 5.5)
    1.6 (0.0 to 8.5)
        Fever 39.5 to <=40 degrees C|
    0.0 (0.0 to 8.0)
    1.4 (0.3 to 4.1)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    2.8 (0.6 to 7.9)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.7)
        Fever >40 degrees C|
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.7)
        Irritability: Any|
    36.4 (22.4 to 52.2)
    50.5 (43.5 to 57.4)
    27.3 (19.8 to 35.9)
    36.4 (17.2 to 59.3)
    36.4 (17.2 to 59.3)
    56.7 (46.7 to 66.4)
    44.4 (34.9 to 54.3)
    24.6 (14.8 to 36.9)
    30.2 (19.2 to 43.0)
        Irritability: Mild|
    20.5 (9.8 to 35.3)
    23.6 (18.0 to 29.9)
    12.5 (7.3 to 19.5)
    22.7 (7.8 to 45.4)
    18.2 (5.2 to 40.3)
    27.9 (19.5 to 37.5)
    19.4 (12.5 to 28.2)
    9.2 (3.5 to 19.0)
    15.9 (7.9 to 27.3)
        Irritability: Moderate|
    15.9 (6.6 to 30.1)
    25.0 (19.3 to 31.4)
    13.3 (7.9 to 20.4)
    13.6 (2.9 to 34.9)
    18.2 (5.2 to 40.3)
    26.0 (17.9 to 35.5)
    24.1 (16.4 to 33.3)
    13.8 (6.5 to 24.7)
    12.7 (5.6 to 23.5)
        Irritability: Severe|
    0.0 (0.0 to 8.0)
    1.9 (0.5 to 4.8)
    1.6 (0.2 to 5.5)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    2.9 (0.6 to 8.2)
    0.9 (0.0 to 5.1)
    1.5 (0.0 to 8.3)
    1.6 (0.0 to 8.5)
        Drowsiness: Any|
    13.6 (5.2 to 27.4)
    34.0 (27.6 to 40.8)
    13.3 (7.9 to 20.4)
    4.5 (0.1 to 22.8)
    22.7 (7.8 to 45.4)
    37.5 (28.2 to 47.5)
    30.6 (22.1 to 40.2)
    13.8 (6.5 to 24.7)
    12.7 (5.6 to 23.5)
        Drowsiness: Mild|
    13.6 (5.2 to 27.4)
    23.6 (18.0 to 29.9)
    10.2 (5.5 to 16.7)
    4.5 (0.1 to 22.8)
    22.7 (7.8 to 45.4)
    24.0 (16.2 to 33.4)
    23.1 (15.6 to 32.2)
    10.8 (4.4 to 20.9)
    1.6 (0.0 to 8.5)
        Drowsiness: Moderate|
    0.0 (0.0 to 8.0)
    8.5 (5.1 to 13.1)
    2.3 (0.5 to 6.7)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    10.6 (5.4 to 18.1)
    6.5 (2.6 to 12.9)
    3.1 (0.4 to 10.7)
    1.6 (0.0 to 8.5)
        Drowsiness: Severe|
    0.0 (0.0 to 8.0)
    1.9 (0.5 to 4.8)
    0.8 (0.0 to 4.3)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    2.9 (0.6 to 8.2)
    0.9 (0.0 to 5.1)
    0.0 (0.0 to 5.5)
    1.6 (0.0 to 8.5)
        Loss of or decreased appetite: Any|
    18.2 (8.2 to 32.7)
    34.4 (28.1 to 41.2)
    18.0 (11.7 to 25.7)
    13.6 (2.9 to 34.9)
    22.7 (7.8 to 45.4)
    33.7 (24.7 to 43.6)
    35.2 (26.2 to 45.0)
    16.9 (8.8 to 28.3)
    19.0 (10.2 to 30.9)
        Loss of or decreased appetite: Mild|
    15.9 (6.6 to 30.1)
    17.0 (12.2 to 22.7)
    12.5 (7.3 to 19.5)
    13.6 (2.9 to 34.9)
    22.7 (7.8 to 45.4)
    15.4 (9.1 to 23.8)
    18.5 (11.7 to 27.1)
    9.2 (3.5 to 19.0)
    15.9 (7.9 to 27.3)
        Loss of or decreased appetite: Moderate|
    0.0 (0.0 to 8.0)
    14.6 (10.2 to 20.1)
    4.7 (1.7 to 9.9)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    14.4 (8.3 to 22.7)
    14.8 (8.7 to 22.9)
    7.7 (2.5 to 17.0)
    1.6 (0.0 to 8.5)
        Loss of or decreased appetite: Severe|
    2.3 (0.1 to 12.0)
    2.8 (1.0 to 6.1)
    0.8 (0.0 to 4.3)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    3.8 (1.1 to 9.6)
    1.9 (0.2 to 6.5)
    0.0 (0.0 to 5.5)
    1.6 (0.0 to 8.5)
        Antipyretic medication use|
    18.2 (8.2 to 32.7)
    34.0 (27.6 to 40.8)
    14.8 (9.2 to 22.2)
    18.2 (5.2 to 40.3)
    18.2 (5.2 to 40.3)
    34.6 (25.6 to 44.6)
    33.3 (24.6 to 43.1)
    13.8 (6.5 to 24.7)
    15.9 (7.9 to 27.3)
    Notes
    [53] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [54] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [55] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [56] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [57] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [58] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [59] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [60] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [61] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Immediate Adverse Event (IAE) Within 30 Days After Vaccination 1

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    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Immediate Adverse Event (IAE) Within 30 Days After Vaccination 1 [62]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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. Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Safety analysis population.
    End point type
    Primary
    End point timeframe
    within 30 Days after Vaccination 1
    Notes
    [62] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [63]
    220 [64]
    132 [65]
    22 [66]
    22 [67]
    110 [68]
    110 [69]
    66 [70]
    66 [71]
    Units: percentage of subjects
    number (confidence interval 95%)
        AE|
    31.8 (18.6 to 47.6)
    40.0 (33.5 to 46.8)
    30.3 (22.6 to 38.9)
    18.2 (5.2 to 40.3)
    45.5 (24.4 to 67.8)
    38.2 (29.1 to 47.9)
    41.8 (32.5 to 51.6)
    33.3 (22.2 to 46.0)
    27.3 (17.0 to 39.6)
        SAE|
    2.3 (0.1 to 12.0)
    1.4 (0.3 to 3.9)
    1.5 (0.2 to 5.4)
    0.0 (0.0 to 15.4)
    4.5 (0.1 to 22.8)
    0.9 (0.0 to 5.0)
    1.8 (0.2 to 6.4)
    1.5 (0.0 to 8.2)
    1.5 (0.0 to 8.2)
        MAE
    11.4 (3.8 to 24.6)
    18.6 (13.7 to 24.4)
    17.4 (11.4 to 25.0)
    9.1 (1.1 to 29.2)
    13.6 (2.9 to 34.9)
    18.2 (11.5 to 26.7)
    19.1 (12.2 to 27.7)
    18.2 (9.8 to 29.6)
    16.7 (8.6 to 27.9)
        NDCMC
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
        IAE
    2.3 (0.1 to 12.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
    Notes
    [63] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [64] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [65] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [66] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [67] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [68] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [69] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [70] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    [71] - N=subjects with 1st dose of vaccine on Month 0 with safety data(Vaccination 1 safety population)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC), Immediate Adverse Event (IAE) Within 30 Days After Vaccination 2

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    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC), Immediate Adverse Event (IAE) Within 30 Days After Vaccination 2 [72]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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. Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Safety analysis population. Here, N signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    within 30 Days after Vaccination 2
    Notes
    [72] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [73]
    213 [74]
    131 [75]
    22 [76]
    22 [77]
    105 [78]
    108 [79]
    66 [80]
    65 [81]
    Units: percentage of subjects
    number (confidence interval 95%)
        AE|
    22.7 (11.5 to 37.8)
    34.3 (27.9 to 41.1)
    28.2 (20.7 to 36.8)
    18.2 (5.2 to 40.3)
    27.3 (10.7 to 50.2)
    34.3 (25.3 to 44.2)
    34.3 (25.4 to 44.0)
    24.2 (14.5 to 36.4)
    32.3 (21.2 to 45.1)
        SAE|
    0.0 (0.0 to 8.0)
    1.9 (0.5 to 4.7)
    0.8 (0.0 to 4.2)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    3.8 (1.0 to 9.5)
    0.0 (0.0 to 3.4)
    1.5 (0.0 to 8.2)
    0.0 (0.0 to 5.5)
        MAE
    11.4 (3.8 to 24.6)
    17.4 (12.5 to 23.1)
    18.3 (12.1 to 26.0)
    13.6 (2.9 to 34.9)
    9.1 (1.1 to 29.2)
    16.2 (9.7 to 24.7)
    18.5 (11.7 to 27.1)
    13.6 (6.4 to 24.3)
    23.1 (13.5 to 35.2)
        NDCMC
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.5)
        IAE
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 2.6)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 5.2)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
    Notes
    [73] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [74] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [75] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [76] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [77] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [78] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [79] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [80] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    [81] - N=subjects with 2nd dose of vaccine on Month 2 with safety data(Vaccination 2 safety population)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC), Immediate Adverse Event (IAE) Within 30 Days After Vaccination 3

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    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE), Newly Diagnosed Chronic Medical Condition (NDCMC), Immediate Adverse Event (IAE) Within 30 Days After Vaccination 3 [82]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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. Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Safety analysis population. Here, N signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    within 30 Days after Vaccination 3
    Notes
    [82] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [83]
    212 [84]
    129 [85]
    22 [86]
    22 [87]
    104 [88]
    108 [89]
    65 [90]
    64 [91]
    Units: percentage of subjects
    number (confidence interval 95%)
        AE|
    29.5 (16.8 to 45.2)
    27.8 (21.9 to 34.4)
    26.4 (19.0 to 34.8)
    18.2 (5.2 to 40.3)
    40.9 (20.7 to 63.6)
    25.0 (17.0 to 34.4)
    30.6 (22.1 to 40.2)
    24.6 (14.8 to 36.9)
    28.1 (17.6 to 40.8)
        SAE|
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.6)
    0.8 (0.0 to 4.2)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    1.0 (0.0 to 5.2)
    0.0 (0.0 to 3.4)
    1.5 (0.0 to 8.3)
    0.0 (0.0 to 5.6)
        MAE
    18.2 (8.2 to 32.7)
    15.1 (10.6 to 20.6)
    16.3 (10.4 to 23.8)
    9.1 (1.1 to 29.2)
    27.3 (10.7 to 50.2)
    13.5 (7.6 to 21.6)
    16.7 (10.2 to 25.1)
    12.3 (5.5 to 22.8)
    20.3 (11.3 to 32.2)
        NDCMC
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.6)
        IAE
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 2.6)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.5)
    0.0 (0.0 to 5.1)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.6)
    Notes
    [83] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [84] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [85] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [86] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [87] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [88] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [89] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [90] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    [91] - N=subjects with 3rd dose of vaccine on Month 6 with safety data(Vaccination 3 safety population)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) Within 30 Days After Any Vaccination

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    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) Within 30 Days After Any Vaccination [92]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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: 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
    [92] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44
    220
    132
    22
    22
    110
    110
    66
    66
    Units: percentage of subjects
    number (confidence interval 95%)
        AE|
    50.0 (34.6 to 65.4)
    58.2 (51.4 to 64.8)
    53.8 (44.9 to 62.5)
    36.4 (17.2 to 59.3)
    63.6 (40.7 to 82.8)
    54.5 (44.8 to 64.1)
    61.8 (52.1 to 70.9)
    53.0 (40.3 to 65.4)
    54.5 (41.8 to 66.9)
        SAE|
    2.3 (0.1 to 12.0)
    3.6 (1.6 to 7.0)
    3.0 (0.8 to 7.6)
    0.0 (0.0 to 15.4)
    4.5 (0.1 to 22.8)
    5.5 (2.0 to 11.5)
    1.8 (0.2 to 6.4)
    4.5 (0.9 to 12.7)
    1.5 (0.0 to 8.2)
        MAE
    31.8 (18.6 to 47.6)
    36.4 (30.0 to 43.1)
    35.6 (27.5 to 44.4)
    22.7 (7.8 to 45.4)
    40.9 (20.7 to 63.6)
    32.7 (24.1 to 42.3)
    40.0 (30.8 to 49.8)
    31.8 (20.9 to 44.4)
    39.4 (27.6 to 52.2)
        NDCMC
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) During the Vaccination Phase

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    End point title
    		 Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) During the Vaccination Phase [93]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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: 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
    [93] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44
    220
    132
    22
    22
    110
    110
    66
    66
    Units: percentage of subjects
    number (confidence interval 95%)
        AE|
    65.9 (50.1 to 79.5)
    70.0 (63.5 to 76.0)
    64.4 (55.6 to 72.5)
    54.5 (32.2 to 75.6)
    77.3 (54.6 to 92.2)
    68.2 (58.6 to 76.7)
    71.8 (62.4 to 80.0)
    65.2 (52.4 to 76.5)
    63.6 (50.9 to 75.1)
        SAE|
    4.5 (0.6 to 15.5)
    7.3 (4.2 to 11.5)
    5.3 (2.2 to 10.6)
    0.0 (0.0 to 15.4)
    9.1 (1.1 to 29.2)
    10.9 (5.8 to 18.3)
    3.6 (1.0 to 9.0)
    4.5 (0.9 to 12.7)
    6.1 (1.7 to 14.8)
        MAE
    40.9 (26.3 to 56.8)
    50.9 (44.1 to 57.7)
    43.2 (34.6 to 52.1)
    36.4 (17.2 to 59.3)
    45.5 (24.4 to 67.8)
    47.3 (37.7 to 57.0)
    54.5 (44.8 to 64.1)
    42.4 (30.3 to 55.2)
    43.9 (31.7 to 56.7)
        NDCMC
    0.0 (0.0 to 8.0)
    0.5 (0.0 to 2.5)
    0.0 (0.0 to 2.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 5.0)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) During the Follow up Phase

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    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC) During the Follow up Phase [94]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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: all subjects who received at least 1 dose of the investigational product (rLP2086 or HAV/saline) and had safety data available. Here, N signifies number of subjects evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    From 1 month after Vaccination 3 (Visit 7) up to 6 months after Vaccination 3 (Visit 8)
    Notes
    [94] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44 [95]
    215 [96]
    128 [97]
    22 [98]
    22 [99]
    108 [100]
    107 [101]
    65 [102]
    63 [103]
    Units: percentage of subjects
    number (confidence interval 95%)
        SAE
    6.8 (1.4 to 18.7)
    2.3 (0.8 to 5.3)
    1.6 (0.2 to 5.5)
    4.5 (0.1 to 22.8)
    9.1 (1.1 to 29.2)
    0.9 (0.0 to 5.1)
    3.7 (1.0 to 9.3)
    1.5 (0.0 to 8.3)
    1.6 (0.0 to 8.5)
        MAE
    31.8 (18.6 to 47.6)
    31.2 (25.0 to 37.8)
    29.7 (21.9 to 38.4)
    22.7 (7.8 to 45.4)
    40.9 (20.7 to 63.6)
    29.6 (21.2 to 39.2)
    32.7 (24.0 to 42.5)
    30.8 (19.9 to 43.4)
    28.6 (17.9 to 41.3)
        NDCMC
    2.3 (0.1 to 12.0)
    0.0 (0.0 to 1.7)
    0.0 (0.0 to 2.8)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 3.4)
    0.0 (0.0 to 5.5)
    0.0 (0.0 to 5.7)
    Notes
    [95] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [96] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [97] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [98] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [99] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [100] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [101] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [102] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    [103] - N=all treated subjects with safety data available from visit 7 to visit 8 (follow up safety set)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC)Throughout the Study

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    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE), Medically Attended Adverse Event (MAE) and Newly Diagnosed Chronic Medical Condition (NDCMC)Throughout the Study [104]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. 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; important medical event. A MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. An NDCMC 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: 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
    [104] - 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: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    44
    220
    132
    22
    22
    110
    110
    66
    66
    Units: percentage of subjects
    number (confidence interval 95%)
        SAE
    9.1 (2.5 to 21.7)
    8.6 (5.3 to 13.2)
    6.1 (2.7 to 11.6)
    4.5 (0.1 to 22.8)
    13.6 (2.9 to 34.9)
    10.9 (5.8 to 18.3)
    6.4 (2.6 to 12.7)
    6.1 (1.7 to 14.8)
    6.1 (1.7 to 14.8)
        MAE
    61.4 (45.5 to 75.6)
    58.6 (51.8 to 65.2)
    56.1 (42.7 to 64.7)
    54.5 (32.2 to 75.6)
    68.2 (45.1 to 86.1)
    54.5 (44.8 to 64.1)
    62.7 (53.0 to 71.8)
    59.1 (46.3 to 71.0)
    53.0 (40.3 to 65.4)
        NDCMC
    2.3 (0.1 to 12.0)
    0.5 (0.0 to 2.5)
    0.0 (0.0 to 2.8)
    4.5 (0.1 to 22.8)
    0.0 (0.0 to 15.4)
    0.0 (0.0 to 3.3)
    0.0 (0.0 to 5.0)
    0.0 (0.0 to 5.4)
    0.0 (0.0 to 5.4)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With hSBA Titer Between 12 Months to Less Than (<) 24 Months >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 3

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    End point title
    		 Percentage of Subjects With hSBA Titer Between 12 Months to Less Than (<) 24 Months >= 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: 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 this endpoint and n signifies number of subjects analyzed at specific time points only.
    End point type
    Secondary
    End point timeframe
    1 Month After Vaccination 3
    End point values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months)
    Number of subjects analysed
    20
    96
    60
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22)| (n =20, 96, 60)
    90.0 (68.3 to 98.8)
    89.6 (81.7 to 94.9)
    5.0 (1.0 to 13.9)
        PMB2001 (A56)| (n =19, 95, 54)
    100.0 (82.4 to 100.0)
    100.0 (96.2 to 100.0)
    1.9 (0.0 to 9.9)
        PMB2948 (B24)| (n =20, 95, 60)
    85.0 (62.1 to 96.8)
    71.6 (61.4 to 80.4)
    5.0 (1.0 to 13.9)
        PMB2707 (B44)| (n =19, 94, 54)
    89.5 (66.9 to 98.7)
    86.2 (77.5 to 92.4)
    0.0 (0.0 to 6.6)
    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

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    End point title
    		 Percentage of Subjects With hSBA Titer >= LLOQ for Each of the 4 Primary MnB Test Strains 1 Month After Vaccination 2
    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: 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 this endpoint and n signifies number of subjects analyzed at specific time points only.
    End point type
    Secondary
    End point timeframe
    1 month (Mon) after Vaccination (Vac) 2
    End point values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    19
    95
    59
    10
    10
    47
    50
    30
    29
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80[A22]| (n=10,9,19,45,50,95,30,29,59)
    78.9 (54.4 to 93.9)
    74.7 (64.8 to 83.1)
    1.7 (0.0 to 9.1)
    90.0 (55.5 to 99.7)
    66.7 (29.9 to 92.5)
    64.4 (48.8 to 78.1)
    84.0 (70.9 to 92.8)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        PMB2001[A56]| (n=9,10,19,47,48,95,23,29,52)
    94.7 (74.0 to 99.9)
    100.0 (96.2 to 100.0)
    0.0 (0.0 to 6.8)
    100.0 (66.4 to 100.0)
    90.0 (55.5 to 99.7)
    100.0 (92.5 to 100.0)
    100.0 (92.6 to 100.0)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        PMB2948[B24]| (n=10,9,19, 42,44,86,30,29, 59)
    57.9 (33.5 to 79.7)
    33.7 (23.9 to 44.7)
    1.7 (0.0 to 9.1)
    70.0 (34.8 to 93.3)
    44.4 (13.7 to 78.8)
    23.8 (12.1 to 39.5)
    43.2 (28.3 to 59.0)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        PMB2707[B44]| (n =9,10,19,47,47,94,23,29,52)
    68.4 (43.4 to 87.4)
    68.1 (57.7 to 77.3)
    0.0 (0.0 to 6.8)
    77.8 (40.0 to 97.2)
    60.0 (26.2 to 87.8)
    72.3 (57.4 to 84.4)
    63.8 (48.5 to 77.3)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
    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

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    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
    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: 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 this endpoint and n signifies number of subjects analyzed at specific time points only.
    End point type
    Secondary
    End point timeframe
    Before Vaccination 1 (T1), 1 month after Vaccination 2 (T2), 1 month after Vaccination 3 (T3)
    End point values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    21
    97
    61
    10
    11
    47
    51
    31
    30
    Units: percentage of subjects
    number (confidence interval 95%)
        T1:PMB80[A22]-1:4(n=9,11,20,46,51,97,31,30,61)
    0.0 (0.0 to 16.8)
    4.1 (1.1 to 10.2)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 28.5)
    4.3 (0.5 to 14.8)
    3.9 (0.5 to 13.5)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB80[A22]-1:8(n=9,11,20,46,51,97,31,30,61)
    0.0 (0.0 to 16.8)
    3.1 (0.6 to 8.8)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 28.5)
    2.2 (0.1 to 11.5)
    3.9 (0.5 to 13.5)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB80[A22]-1:16(n=9,11,20,46,51,97,31,30,61)
    0.0 (0.0 to 16.8)
    3.1 (0.6 to 8.8)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 28.5)
    2.2 (0.1 to 11.5)
    3.9 (0.5 to 13.5)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB80[A22]-1:32(n=9,11,20,46,51,97,31,30,61)
    0.0 (0.0 to 16.8)
    2.1 (0.3 to 7.3)
    0.0 (0.0 to 5.9)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 28.5)
    2.2 (0.1 to 11.5)
    2.0 (0.0 to 10.4)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.6)
        T1:PMB80[A22]-1:64(n=9,11,20,46,51,97,31,30,61)
    0.0 (0.0 to 16.8)
    1.0 (0.0 to 5.6)
    0.0 (0.0 to 5.9)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 28.5)
    2.2 (0.1 to 11.5)
    0.0 (0.0 to 7.0)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.6)
        T1:PMB80[A22]-1:128(n=9,11,20,46,51,97,31,30,61)
    0.0 (0.0 to 16.8)
    1.0 (0.0 to 5.6)
    0.0 (0.0 to 5.9)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 28.5)
    2.2 (0.1 to 11.5)
    0.0 (0.0 to 7.0)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.6)
        T1:PMB2001(A56)-1:4(n=9,10,19,46,49,95,24,29,53)
    0.0 (0.0 to 17.6)
    2.1 (0.3 to 7.4)
    1.9 (0.0 to 10.1)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    4.1 (0.5 to 14.0)
    4.2 (0.1 to 21.1)
    0.0 (0.0 to 11.9)
        T1:PMB2001(A56)-1:8(n=9,10,19,46,49,95,24,29,53)
    0.0 (0.0 to 17.6)
    1.1 (0.0 to 5.7)
    0.0 (0.0 to 6.7)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    2.0 (0.1 to 10.9)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.9)
        T1:PMB2001(A56)-1:16(n=9,10,19,46,49,95,24,29,53)
    0.0 (0.0 to 17.6)
    1.1 (0.0 to 5.7)
    0.0 (0.0 to 6.7)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    2.0 (0.1 to 10.9)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.9)
        T1:PMB2001(A56)-1:32(n=9,10,19,46,49,95,24,29,53)
    0.0 (0.0 to 17.6)
    1.1 (0.0 to 5.7)
    0.0 (0.0 to 6.7)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    2.0 (0.1 to 10.9)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.9)
        T1:PMB2001(A56)-1:64(n=9,10,19,46,49,95,24,29,53)
    0.0 (0.0 to 17.6)
    0.0 (0.0 to 3.8)
    0.0 (0.0 to 6.7)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.9)
        T1:PMB2001(A56)-1:128,n=9,10,19,46,49,95,24,29,53
    0.0 (0.0 to 17.6)
    0.0 (0.0 to 3.8)
    0.0 (0.0 to 6.7)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.9)
        T1:PMB2948(B24)-1:4(n=10,11,21,46,51,97,31,30,61)
    4.8 (0.1 to 23.8)
    2.1 (0.3 to 7.3)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 30.8)
    9.1 (0.2 to 41.3)
    2.2 (0.1 to 11.5)
    2.0 (0.0 to 10.4)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB2948(B24)-1:8(n=10,11,21,46,51,97,31,30,61)
    4.8 (0.1 to 23.8)
    2.1 (0.3 to 7.3)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 30.8)
    9.1 (0.2 to 41.3)
    2.2 (0.1 to 11.5)
    2.0 (0.0 to 10.4)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB2948(B24)-1:16,n=10,11,21,46,51,97,31,30,61
    4.8 (0.1 to 23.8)
    2.1 (0.3 to 7.3)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 30.8)
    9.1 (0.2 to 41.3)
    2.2 (0.1 to 11.5)
    2.0 (0.0 to 10.4)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB2948(B24)-1:32,n=10,11,21,46,51,97,31,30,61
    4.8 (0.1 to 23.8)
    0.0 (0.0 to 3.7)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 30.8)
    9.1 (0.2 to 41.3)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.0)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB2948(B24)-1:64,n=10,11,21,46,51,97,31,30,61
    0.0 (0.0 to 16.1)
    0.0 (0.0 to 3.7)
    1.6 (0.0 to 8.8)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 28.5)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.0)
    0.0 (0.0 to 11.2)
    3.3 (0.1 to 17.2)
        T1:PMB2948(B24)-1:128n=10,11,21,46,51,97,31,30,61
    0.0 (0.0 to 16.1)
    0.0 (0.0 to 3.7)
    0.0 (0.0 to 5.9)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 28.5)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.0)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.6)
        T1:PMB2707(B44)-1:4(n=9,10,19,46,49,95,24,30,54)
    0.0 (0.0 to 17.6)
    1.1 (0.0 to 5.7)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    2.2 (0.1 to 11.5)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T1:PB2707(B44)-1:8(n=9,10,19,46,49,95,24,30,54)
    0.0 (0.0 to 17.6)
    1.1 (0.0 to 5.7)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    2.2 (0.1 to 11.5)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T1:PMB2707(B44)-1:16(n=9,10,19,46,49,95,24,30,54)
    0.0 (0.0 to 17.6)
    0.0 (0.0 to 3.8)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T1:PMB2707(B44)-1:32(n=9,10,19,46,49,95,24,30,54)
    0.0 (0.0 to 17.6)
    0.0 (0.0 to 3.8)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T1:PMB2707(B44)-1:64(n=9,10,19,46,49,95,24,30,54)
    0.0 (0.0 to 17.6)
    0.0 (0.0 to 3.8)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T1:PMB2707(B44)-1:128,n=9,10,19,46,49,95,24,30,54
    0.0 (0.0 to 17.6)
    0.0 (0.0 to 3.8)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 33.6)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 7.7)
    0.0 (0.0 to 7.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T2:PMB80[A22]-1:4(n=10,9,19,45,50,95,30,29,59)
    78.9 (54.4 to 93.9)
    75.8 (65.9 to 84.0)
    1.7 (0.0 to 9.1)
    90.0 (55.5 to 99.7)
    66.7 (29.9 to 92.5)
    64.4 (48.8 to 78.1)
    86.0 (73.3 to 94.2)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB80[A22]-1:8(n=10,9,19,45,50,95,30,29,59)
    78.9 (54.4 to 93.9)
    75.8 (65.9 to 84.0)
    1.7 (0.0 to 9.1)
    90.0 (55.5 to 99.7)
    66.7 (29.9 to 92.5)
    64.4 (48.8 to 78.1)
    86.0 (73.3 to 94.2)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB80[A22]-1:32(n=10,9,19,45,50,95,30,29,59)
    63.2 (38.4 to 83.7)
    58.9 (48.4 to 68.9)
    1.7 (0.0 to 9.1)
    80.0 (44.5 to 97.5)
    44.4 (13.7 to 78.8)
    51.1 (35.8 to 66.3)
    66.0 (51.2 to 78.8)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB80[A22]-1:64(n=10,9,19,45,50,95,30,29,59)
    36.8 (16.3 to 61.6)
    34.7 (25.3 to 45.2)
    1.7 (0.0 to 9.1)
    50.0 (18.7 to 81.3)
    22.2 (2.8 to 60.0)
    28.9 (16.4 to 44.3)
    40.0 (26.4 to 54.8)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB80[A22]-1:128(n =10,9,19,45,50,95,30,29,59)
    21.1 (6.1 to 45.6)
    13.7 (7.5 to 22.3)
    1.7 (0.0 to 9.1)
    20.0 (2.5 to 55.6)
    22.2 (2.8 to 60.0)
    11.1 (3.7 to 24.1)
    16.0 (7.2 to 29.1)
    0.0 (0.0 to 11.6)
    0.0 (0.0 to 11.9)
        T2:PMB200[A56]-1:4(n=9,10,19,47,48,95,23,29,52)
    100.0 (82.4 to 100.0)
    100.0 (96.2 to 100.0)
    1.9 (0.0 to 10.3)
    100.0 (66.4 to 100.0)
    100.0 (69.2 to 100.0)
    100.0 (92.5 to 100.0)
    100.0 (92.6 to 100.0)
    4.3 (0.1 to 21.9)
    0.0 (0.0 to 11.9)
        T2:PMB2001[A56]-1:16(n=9,10,19,47,48,95,23,29,52)
    94.7 (74.0 to 99.9)
    100.0 (96.2 to 100.0)
    0.0 (0.0 to 6.8)
    100.0 (66.4 to 100.0)
    90.0 (55.5 to 99.7)
    100.0 (92.5 to 100.0)
    100.0 (92.6 to 100.0)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2001[A56]-1:32(n =9,10,19,47,48,95,23,29,52)
    94.7 (74.0 to 99.9)
    95.8 (89.6 to 98.8)
    0.0 (0.0 to 6.8)
    100.0 (66.4 to 100.0)
    90.0 (55.5 to 99.7)
    95.7 (85.5 to 99.5)
    95.8 (85.7 to 99.5)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2001[A56]-1:64(n =9,10,19,47,48,95,23,29,52)
    84.2 (60.4 to 96.6)
    86.3 (77.7 to 92.5)
    0.0 (0.0 to 6.8)
    100.0 (66.4 to 100.0)
    70.0 (34.8 to 93.3)
    87.2 (74.3 to 95.2)
    85.4 (72.2 to 93.9)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2001[A56]-1:128,n=9,10,19,47,48,95,23,29,52
    47.4 (24.4 to 71.1)
    56.8 (46.3 to 67.0)
    0.0 (0.0 to 6.8)
    44.4 (13.7 to 78.8)
    50.0 (18.7 to 81.3)
    59.6 (44.3 to 73.6)
    54.2 (39.2 to 68.8)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2948(B24)-1:4(n=10,9,19,42,44,86,30,29,59)
    57.9 (33.5 to 79.7)
    36.0 (26.0 to 47.1)
    1.7 (0.0 to 9.1)
    70.0 (34.8 to 93.3)
    44.4 (13.7 to 78.8)
    28.6 (15.7 to 44.6)
    43.2 (28.3 to 59.0)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB2948(B24)-1:16(n=10,9,19,42,44,86,30,29,59)
    47.4 (24.4 to 71.7)
    32.6 (22.8 to 43.5)
    1.7 (0.0 to 9.1)
    60.0 (26.2 to 87.8)
    33.3 (7.5 to 70.1)
    21.4 (10.3 to 36.8)
    43.2 (28.3 to 59.0)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB2948(B24)-1:32(n=10,9,19,42,44,86,30,29,59)
    5.3 (0.1 to 26.0)
    14.0 (7.4 to 23.1)
    1.7 (0.0 to 9.1)
    10.0 (0.3 to 44.5)
    0.0 (0.0 to 33.6)
    9.5 (2.7 to 22.6)
    18.2 (8.2 to 32.7)
    0.0 (0.0 to 11.6)
    3.4 (0.1 to 17.8)
        T2:PMB2948(B24)-1:64(n=10,9,19,42,44,86,30,29,59)
    0.0 (0.0 to 17.6)
    3.5 (0.7 to 9.9)
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 33.6)
    2.4 (0.1 to 12.6)
    4.5 (0.6 to 15.5)
    0.0 (0.0 to 11.6)
    0.0 (0.0 to 11.9)
        T2:PMB2948(B24)-1:128,n=10,9,19,42,44,86,30,29,59
    0.0 (0.0 to 17.6)
    1.2 (0.0 to 6.3)
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 30.8)
    0.0 (0.0 to 33.6)
    2.4 (0.1 to 12.6)
    0.0 (0.0 to 8.0)
    0.0 (0.0 to 11.6)
    0.0 (0.0 to 11.9)
        T2:PMB2707(B44)-1:4(n= 9,10,19,47,47,94,23,29,52)
    73.7 (48.8 to 90.9)
    68.1 (57.7 to 77.3)
    0.0 (0.0 to 6.8)
    77.8 (40.0 to 97.2)
    70.0 (34.8 to 93.3)
    72.3 (57.4 to 84.4)
    63.8 (48.5 to 77.3)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2707(B44)-1:16(n=9,10,19,47,47,94,23,29,52)
    68.4 (43.4 to 87.4)
    67.0 (56.6 to 76.4)
    0.0 (0.0 to 6.8)
    77.8 (40.0 to 97.2)
    60.0 (26.2 to 87.8)
    72.3 (57.4 to 84.4)
    61.7 (46.4 to 75.5)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2707(B44)-1:32(n=9,10,19,47,47,94,23,29,52)
    57.9 (33.5 to 79.7)
    56.4 (45.8 to 66.6)
    0.0 (0.0 to 6.8)
    55.6 (21.2 to 86.3)
    60.0 (26.2 to 87.8)
    61.7 (46.4 to 75.5)
    51.1 (36.1 to 65.9)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB2707(B44)-1:64(n=9,10,19,47,47,94,23,29,52)
    31.6 (12.6 to 56.6)
    24.5 (16.2 to 34.4)
    0.0 (0.0 to 6.8)
    33.3 (7.5 to 70.1)
    30.0 (6.7 to 65.2)
    27.7 (15.6 to 42.6)
    21.3 (10.7 to 35.7)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T2:PMB270(B44)-1:128(n=9,10,19,47,47,94,23,29,52)
    10.5 (1.3 to 33.1)
    10.6 (5.2 to 18.7)
    0.0 (0.0 to 6.8)
    11.1 (0.3 to 48.2)
    10.0 (0.3 to 44.5)
    10.6 (3.5 to 23.1)
    10.6 (3.5 to 23.1)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 11.9)
        T3:PMB80(A22)-1:4(n=9,11,20,45,51,96,31,29,60)
    90.0 (68.3 to 98.8)
    89.6 (81.7 to 94.9)
    6.7 (1.8 to 16.2)
    88.9 (51.8 to 99.7)
    90.9 (58.7 to 99.8)
    91.1 (78.8 to 97.5)
    88.2 (76.1 to 95.6)
    6.5 (0.8 to 21.4)
    6.9 (0.8 to 22.8)
        T3:PMB80(A22)-1:8(n=9,11,20,45,51,96,31,29,60)
    90.0 (68.3 to 98.8)
    89.6 (81.7 to 94.9)
    6.7 (1.8 to 16.2)
    88.9 (51.8 to 99.7)
    90.9 (58.7 to 99.8)
    91.1 (78.8 to 97.5)
    88.2 (76.1 to 95.6)
    6.5 (0.8 to 21.4)
    6.9 (0.8 to 22.8)
        T3:PMB80(A22)-1:32(n=9,11,20,45,51,96,31,29,60)
    85.0 (62.1 to 96.8)
    84.4 (75.5 to 91.0)
    3.3 (0.4 to 11.5)
    88.9 (51.8 to 99.7)
    81.8 (48.2 to 97.7)
    82.2 (67.9 to 92.0)
    86.3 (73.7 to 94.3)
    3.2 (0.1 to 16.7)
    3.4 (0.1 to 17.8)
        T3:PMB80(A22)-1:64(n=9,11,20,45,51,96,31,29,60)
    70.0 (45.7 to 88.1)
    66.7 (56.3 to 76.0)
    1.7 (0.0 to 8.9)
    66.7 (29.9 to 92.5)
    72.7 (39.0 to 94.0)
    60.0 (44.3 to 74.3)
    72.5 (58.3 to 84.1)
    3.2 (0.1 to 16.7)
    0.0 (0.0 to 11.9)
        T3:PMB80(A22)-1:128(n=9,11,20,45,51,96,31,29,60)
    50.0 (27.2 to 72.8)
    43.8 (33.6 to 54.3)
    0.0 (0.0 to 6.1)
    44.4 (13.7 to 78.8)
    54.5 (23.4 to 83.3)
    37.8 (23.8 to 53.5)
    49.0 (34.8 to 63.4)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.9)
        T3:PMB2001(A56)-1:4(n=9,10,19,47,48,95,24,30,54)
    100.0 (82.4 to 100.0)
    100.0 (96.2 to 100.0)
    9.3 (3.1 to 20.3)
    100.0 (66.4 to 100.0)
    100.0 (69.2 to 100.0)
    100.0 (92.5 to 100.0)
    100.0 (92.6 to 100.0)
    8.3 (1.0 to 27.0)
    10.0 (2.1 to 26.5)
        T3:PMB2001(A56)-1:16(n=9,10,19,47,48,95,24,30,54)
    100.0 (82.4 to 100.0)
    98.9 (94.3 to 100.0)
    1.9 (0.0 to 9.9)
    100.0 (66.4 to 100.0)
    100.0 (69.2 to 100.0)
    97.9 (88.7 to 99.9)
    100.0 (92.6 to 100.0)
    0.0 (0.0 to 14.2)
    3.3 (0.1 to 7.2)
        T3:PMB2001(A56)-1:32(n=9,10,19,47,48,95,24,30,54)
    94.7 (74.0 to 99.9)
    95.8 (89.6 to 98.8)
    1.9 (0.0 to 9.9)
    100.0 (66.4 to 100.0)
    90.0 (55.5 to 99.7)
    97.9 (88.7 to 99.9)
    93.8 (82.8 to 98.7)
    0.0 (0.0 to 14.2)
    3.3 (0.1 to 17.2)
        T3:PMB2001(A56)-1:64(n=9,10,19,47,48,95,24,30,54)
    89.5 (66.9 to 98.7)
    89.5 (81.5 to 94.8)
    0.0 (0.0 to 6.6)
    100.0 (66.4 to 100.0)
    80.0 (44.4 to 97.5)
    93.6 (82.5 to 98.7)
    85.4 (72.2 to 93.9)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T3:PMB2001(A56)-1:128,n=9,10,19,47,48,95,24,30,54
    68.4 (43.4 to 87.4)
    83.2 (74.1 to 90.1)
    0.0 (0.0 to 6.6)
    55.6 (21.2 to 86.3)
    80.0 (44.4 to 97.5)
    89.4 (76.9 to 96.5)
    77.1 (62.7 to 88.0)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T3:PMB2948(B24)-1:4(n=9,11,20,45,50,95,31,29,60)
    85.0 (62.1 to 96.8)
    71.6 (61.4 to 80.4)
    5.0 (1.0 to 13.9)
    88.9 (51.8 to 99.7)
    81.8 (48.2 to 97.7)
    71.1 (55.7 to 83.6)
    72.0 (57.5 to 83.8)
    3.2 (0.1 to 16.7)
    6.9 (0.8 to 22.8)
        T3:PMB2948(B24)-1:16(n=9,11,20,45,50,95,31,29,60)
    75.0 (50.9 to 91.3)
    67.4 (57.0 to 76.6)
    5.0 (1.0 to 13.9)
    88.9 (51.8 to 99.7)
    63.6 (30.8 to 89.1)
    66.7 (51.0 to 80.0)
    68.0 (53.3 to 80.5)
    3.2 (0.1 to 16.7)
    6.9 (0.8 to 22.8)
        T3:PMB2948(B24)-1:32(n=9,11,20,45,50,95,31,29,60)
    40.0 (19.1 to 63.9)
    35.8 (26.2 to 46.3)
    1.7 (0.0 to 8.9)
    44.4 (13.7 to 78.8)
    36.4 (10.9 to 69.2)
    37.8 (23.8 to 53.5)
    34.0 (21.2 to 48.8)
    3.2 (0.1 to 16.7)
    0.0 (0.0 to 11.9)
        T3:PMB2948(B24)-1:64(n=9,11,20,45,50,95,31,29,60)
    15.0 (3.2 to 37.9)
    13.7 (7.5 to 22.3)
    0.0 (0.0 to 6.0)
    11.1 (0.3 to 48.2)
    18.2 (2.3 to 51.8)
    17.8 (8.0 to 32.1)
    10.0 (3.3 to 21.8)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.9)
        T3:PMB2948(B24)-1:128,n=9,11,20,45,50,95,31,29,60
    5.0 (0.1 to 24.9)
    2.1 (0.3 to 7.4)
    0.0 (0.0 to 6.0)
    0.0 (0.0 to 33.6)
    9.1 (0.2 to 41.3)
    2.2 (0.1 to 11.8)
    2.0 (0.1 to 10.6)
    0.0 (0.0 to 11.2)
    0.0 (0.0 to 11.9)
        T3:PMB2707(B44)-1:4(n=9,10,19,47,47,94,24,30,54)
    89.5 (66.9 to 98.7)
    87.2 (78.8 to 93.2)
    0.0 (0.0 to 6.6)
    88.9 (51.8 to 99.7)
    90.0 (55.5 to 99.7)
    87.2 (74.3 to 95.2)
    87.2 (74.3 to 95.2)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T3:PMB2707(B44)-1:16(n=9,10,19,47,47,94,24,30,54)
    84.2 (60.4 to 96.6)
    86.2 (77.5 to 92.4)
    0.0 (0.0 to 6.6)
    77.8 (40.0 to 97.2)
    90.0 (55.5 to 99.7)
    87.2 (74.3 to 95.2)
    85.1 (71.7 to 93.8)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T3:PMB2707(B44)-1:32(n=9,10,19,47,47,94,24,30,54)
    63.2 (38.4 to 83.7)
    76.6 (66.7 to 84.7)
    0.0 (0.0 to 6.6)
    55.6 (21.2 to 86.3)
    70.0 (34.8 to 93.3)
    74.5 (59.7 to 86.1)
    78.7 (64.3 to 89.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T3:PMB2707(B44)-1:64(n=9,10,19,47,47,94,24,30,54
    36.8 (16.3 to 61.6)
    58.5 (47.9 to 68.6)
    0.0 (0.0 to 6.6)
    44.4 (13.7 to 78.8)
    30.0 (6.7 to 65.2)
    57.4 (42.2 to 71.7)
    59.6 (44.3 to 73.6)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
        T3:PMB2707(B44)-1:128,n=9,10,19,47,47,94,24,30,54
    21.1 (6.1 to 45.6)
    31.9 (22.7 to 42.3)
    0.0 (0.0 to 6.6)
    22.2 (2.8 to 60.0)
    20.0 (2.5 to 55.6)
    29.8 (17.3 to 44.9)
    34.0 (20.9 to 49.3)
    0.0 (0.0 to 14.2)
    0.0 (0.0 to 11.6)
    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

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    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
    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: 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 this endpoint and n signifies number of subjects analyzed at specific time points only. Here, 99999 represents that 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)
    End point values
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 1: 60-µg bivalent rLP2086 (>=12 months to <18 months) Group 1: 60-µg bivalent rLP2086 (>=18 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <18 months) Group 2: 120-µg bivalent rLP2086 (>=18 months to <24 months) Group 3: HAV/Saline (>=12 months to <18 months) Group 3: HAV/Saline (>=18 months to <24 months)
    Number of subjects analysed
    21
    97
    61
    10
    11
    47
    51
    31
    30
    Units: titers
    geometric mean (confidence interval 95%)
        T1:PMB80(A22(n=9,11,20,46,51,97,31,30,61)
    8.0 (-99999 to 99999)
    8.4 (7.9 to 9.0)
    8.1 (7.9 to 8.3)
    8.0 (-99999 to 99999)
    8.0 (-99999 to 99999)
    8.5 (7.5 to 9.6)
    8.3 (7.8 to 8.9)
    8.0 (-99999 to 99999)
    8.2 (7.8 to 8.8)
        T1:PMB2001(A56)(n=9,10,19,46,49,95,24,29,53)
    4.0 (-99999 to 99999)
    4.1 (3.9 to 4.3)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    4.2 (3.8 to 4.5)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
        T1:PMB2948(B24)(n=10, 11,21,46,51,97,31,30,61)
    4.4 (3.6 to 5.4)
    4.1 (4.0 to 4.3)
    4.2 (3.8 to 4.6)
    4.0 (-99999 to 99999)
    4.8 (3.2 to 7.4)
    4.1 (3.9 to 4.4)
    4.1 (3.9 to 4.3)
    4.0 (-99999 to 99999)
    4.4 (3.6 to 5.3)
        T1:PMB2707(B44)(n=9,10,19,46,49,95,24, 30,54)
    4.0 (-99999 to 99999)
    4.0 (4.0 to 4.1)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    4.1 (3.9 to 4.2)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
        T2:PMB80(A22)(n=10,9,19,45,50,95,30,29,59)
    32.0 (19.7 to 52.0)
    30.4 (24.3 to 38.1)
    8.3 (7.7 to 8.9)
    42.2 (22.6 to 79.1)
    23.5 (10.1 to 54.9)
    24.6 (17.8 to 34.2)
    36.8 (26.9 to 50.3)
    8.0 (-99999 to 99999)
    8.6 (7.4 to 10.0)
        T2:PMB2001(A56)(n =9,10,19,47,48,95,23,29,52)
    82.6 (51.4 to 132.9)
    110.6 (92.0 to 133.0)
    4.0 (-99999 to 99999)
    101.6 (64.0 to 161.2)
    68.6 (28.2 to 166.8)
    117.2 (89.7 to 153.0)
    104.6 (80.4 to 136.0)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
        T2:PMB2948(B24)(n =10,9,19,42,44,86,30,29,59)
    8.6 (6.1 to 12.2)
    7.2 (5.9 to 8.7)
    4.1 (3.9 to 4.4)
    10.6 (6.2 to 18.0)
    6.9 (4.1 to 11.5)
    6.0 (4.7 to 7.8)
    8.5 (6.4 to 11.3)
    4.0 (-99999 to 99999)
    4.3 (3.7 to 5.0)
        T2:PMB2707(B44)(n=9,10,19,47,47,94,23,29,52)
    22.2 (11.2 to 43.9)
    19.4 (15.1 to 24.9)
    40 (-99999 to 99999)
    23.5 (9.3 to 59.4)
    21.1 (6.5 to 68.3)
    22.1 (15.5 to 31.6)
    17.0 (11.8 to 24.4)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
        T3:PMB80(A22)(n=9,11,20,45,51,96,31,29,60)
    81.6 (46.6 to 142.8)
    67.3 (53.7 to 84.3)
    8.6 (7.9 to 9.3)
    80.6 (30.9 to 210.7)
    82.3 (36.5 to 185.8)
    63.0 (44.5 to 89.3)
    71.4 (52.7 to 96.6)
    8.6 (7.5 to 9.8)
    8.6 (7.7 to 9.6)
        T3:PMB2001(A56)(n=9, 10,19,47,48,95,24,30,54)
    142.8 (85.5 to 238.6)
    171.4 (141.6 to 207.4)
    4.2 (3.8 to 4.5)
    109.7 (70.4 to 171.1)
    181.0 (68.6 to 477.9)
    190.6 (146.9 to 247.4)
    154.4 (116.3 to 205.1)
    4.0 (-99999 to 99999)
    4.3 (3.7 to 4.9)
        T3:PMB2948(B24)(n =9,11,20,45,50,95,31, 29,60)
    18.4 (11.8 to 28.6)
    15.1 (12.3 to 18.6)
    4.3 (3.9 to 4.8)
    20.2 (11.1 to 36.6)
    17.0 (8.2 to 35.5)
    15.8 (11.4 to 21.8)
    14.5 (11.1 to 19.1)
    4.3 (3.7 to 4.9)
    4.4 (3.8 to 5.0)
        T3:PMB2707(B44)(n =9,10,19,47,94,24,30,54)
    32.0 (18.3 to 55.8)
    45.6 (35.2 to 59.0)
    4.0 (-99999 to 99999)
    29.6 (11.6 to 75.8)
    34.3 (15.0 to 78.2)
    46.3 (31.6 to 67.8)
    44.9 (31.3 to 64.5)
    4.0 (-99999 to 99999)
    4.0 (-99999 to 99999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs: Recorded from Vaccination 1 through 6 months after Vaccination 3. Subjects recorded local reactions and systemic events in e-diary within 7 days after Vaccination 1, 2 and 3. NSAEs: Recorded from Vaccination 1 through 1 month after Vaccination 3.
    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
    20.0
    Reporting groups
    Reporting group title
    Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of 60 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Reporting group title
    Group 3: HAV/Saline (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of saline on 2- month and HAV vaccine on a 0-, 6- month schedule.

    Reporting group title
    Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months)
    Reporting group description
    		 Subjects from >=12 months to <24 months of age, received intramuscular injection of 120 µg of bivalent rLP2086 vaccine on a 0-, 2-, 6- month schedule.

    Serious adverse events
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 44 (9.09%)
    8 / 132 (6.06%)
    19 / 220 (8.64%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Accidental exposure to product
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebellar ataxia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Crying
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Eyelid ptosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Enteritis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polydipsia psychogenic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Croup infectious
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterovirus infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    3 / 220 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media chronic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    3 / 220 (1.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral tonsillitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Group 1: 60-µg bivalent rLP2086 (>=12 months to <24 months) Group 3: HAV/Saline (>=12 months to <24 months) Group 2: 120-µg bivalent rLP2086 (>=12 months to <24 months)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 44 (97.73%)
    113 / 132 (85.61%)
    209 / 220 (95.00%)
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    3 / 220 (1.36%)
         occurrences all number
    0
    0
    3
    Injection site erythema
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Injection site erythema (redness)
    alternative assessment type: Systematic
         subjects affected / exposed
    30 / 44 (68.18%)
    28 / 132 (21.21%)
    137 / 220 (62.27%)
         occurrences all number
    59
    40
    249
    Injection site pain (tenderness at injection site)
    alternative assessment type: Systematic
         subjects affected / exposed
    35 / 44 (79.55%)
    41 / 132 (31.06%)
    160 / 220 (72.73%)
         occurrences all number
    72
    62
    361
    Injection site pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    4 / 220 (1.82%)
         occurrences all number
    1
    0
    5
    Injection site swelling (swelling)
    alternative assessment type: Systematic
         subjects affected / exposed
    17 / 44 (38.64%)
    20 / 132 (15.15%)
    103 / 220 (46.82%)
         occurrences all number
    33
    26
    154
    Pyrexia
         subjects affected / exposed
    1 / 44 (2.27%)
    6 / 132 (4.55%)
    18 / 220 (8.18%)
         occurrences all number
    1
    6
    18
    Vaccination site pain
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 132 (0.76%)
    2 / 220 (0.91%)
         occurrences all number
    1
    1
    2
    Vessel puncture site bruise
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia (fever)
    alternative assessment type: Systematic
         subjects affected / exposed
    16 / 44 (36.36%)
    20 / 132 (15.15%)
    82 / 220 (37.27%)
         occurrences all number
    23
    22
    118
    Immune system disorders
    Food allergy
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 132 (2.27%)
    8 / 220 (3.64%)
         occurrences all number
    1
    3
    9
    Rhinorrhoea
         subjects affected / exposed
    2 / 44 (4.55%)
    2 / 132 (1.52%)
    11 / 220 (5.00%)
         occurrences all number
    2
    3
    14
    Rhinitis allergic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences all number
    1
    0
    3
    Psychiatric disorders
    Irritability
         subjects affected / exposed
    5 / 44 (11.36%)
    5 / 132 (3.79%)
    21 / 220 (9.55%)
         occurrences all number
    6
    7
    31
    Irritability1
    alternative assessment type: Systematic
         subjects affected / exposed
    31 / 44 (70.45%)
    69 / 132 (52.27%)
    176 / 220 (80.00%)
         occurrences all number
    61
    116
    369
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    3 / 220 (1.36%)
         occurrences all number
    0
    1
    4
    Arthropod sting
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Concussion
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 132 (2.27%)
    0 / 220 (0.00%)
         occurrences all number
    0
    3
    0
    Contusion
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    5 / 220 (2.27%)
         occurrences all number
    0
    2
    6
    Craniocerebral injury
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    0 / 220 (0.00%)
         occurrences all number
    0
    2
    0
    Excoriation
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences all number
    1
    1
    0
    Face injury
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    0 / 220 (0.00%)
         occurrences all number
    0
    2
    0
    Fall
         subjects affected / exposed
    2 / 44 (4.55%)
    7 / 132 (5.30%)
    5 / 220 (2.27%)
         occurrences all number
    2
    9
    6
    Hand fracture
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Laceration
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    4 / 220 (1.82%)
         occurrences all number
    1
    0
    4
    Lip injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    3 / 220 (1.36%)
         occurrences all number
    0
    0
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    2
    0
    0
    Somnolence (drowsiness)
    alternative assessment type: Systematic
         subjects affected / exposed
    23 / 44 (52.27%)
    40 / 132 (30.30%)
    127 / 220 (57.73%)
         occurrences all number
    32
    56
    234
    Somnolence
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    3 / 220 (1.36%)
         occurrences all number
    0
    3
    3
    Ear and labyrinth disorders
    Eustachian tube disorder
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 132 (0.76%)
    1 / 220 (0.45%)
         occurrences all number
    1
    1
    1
    Middle ear effusion
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 132 (2.27%)
    8 / 220 (3.64%)
         occurrences all number
    0
    4
    9
    Eye disorders
    Anisometropia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Astigmatism
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Conjunctivitis allergic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Hypermetropia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences all number
    1
    0
    1
    Gastrointestinal disorders
    Aphthous ulcer
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 132 (0.00%)
    1 / 220 (0.45%)
         occurrences all number
    3
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 44 (2.27%)
    5 / 132 (3.79%)
    11 / 220 (5.00%)
         occurrences all number
    2
    6
    15
    Enteritis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Flatulence
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Teething
         subjects affected / exposed
    0 / 44 (0.00%)
    4 / 132 (3.03%)
    8 / 220 (3.64%)
         occurrences all number
    0
    5
    10
    Vomiting
         subjects affected / exposed
    1 / 44 (2.27%)
    5 / 132 (3.79%)
    8 / 220 (3.64%)
         occurrences all number
    1
    5
    8
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 132 (1.52%)
    4 / 220 (1.82%)
         occurrences all number
    1
    2
    4
    Dermatitis contact
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    4 / 220 (1.82%)
         occurrences all number
    0
    1
    4
    Dermatitis diaper
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    3 / 220 (1.36%)
         occurrences all number
    0
    0
    3
    Dermatitis
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 132 (2.27%)
    3 / 220 (1.36%)
         occurrences all number
    0
    3
    3
    Eczema
         subjects affected / exposed
    0 / 44 (0.00%)
    4 / 132 (3.03%)
    4 / 220 (1.82%)
         occurrences all number
    0
    4
    4
    Miliaria
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 132 (0.76%)
    1 / 220 (0.45%)
         occurrences all number
    2
    1
    1
    Rash generalised
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Rash
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    3 / 220 (1.36%)
         occurrences all number
    0
    1
    3
    Urticaria
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    4 / 220 (1.82%)
         occurrences all number
    0
    2
    5
    Musculoskeletal and connective tissue disorders
    Synovitis
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    0 / 220 (0.00%)
         occurrences all number
    0
    2
    0
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    3 / 220 (1.36%)
         occurrences all number
    0
    2
    4
    Bronchitis
         subjects affected / exposed
    5 / 44 (11.36%)
    11 / 132 (8.33%)
    22 / 220 (10.00%)
         occurrences all number
    9
    12
    27
    Cellulitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences all number
    1
    0
    2
    Conjunctivitis
         subjects affected / exposed
    1 / 44 (2.27%)
    13 / 132 (9.85%)
    22 / 220 (10.00%)
         occurrences all number
    1
    15
    23
    Croup infectious
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    9 / 220 (4.09%)
         occurrences all number
    0
    2
    9
    Enterobiasis
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    2 / 220 (0.91%)
         occurrences all number
    0
    2
    2
    Gastroenteritis viral
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 132 (2.27%)
    10 / 220 (4.55%)
         occurrences all number
    1
    4
    12
    Exanthema subitum
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 132 (0.00%)
    3 / 220 (1.36%)
         occurrences all number
    0
    0
    3
    Gastroenteritis
         subjects affected / exposed
    4 / 44 (9.09%)
    11 / 132 (8.33%)
    29 / 220 (13.18%)
         occurrences all number
    5
    11
    35
    Hand-foot-and-mouth disease
         subjects affected / exposed
    2 / 44 (4.55%)
    6 / 132 (4.55%)
    10 / 220 (4.55%)
         occurrences all number
    2
    6
    11
    Impetigo
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 132 (2.27%)
    3 / 220 (1.36%)
         occurrences all number
    1
    3
    3
    Laryngitis
         subjects affected / exposed
    2 / 44 (4.55%)
    5 / 132 (3.79%)
    3 / 220 (1.36%)
         occurrences all number
    3
    5
    3
    Infected bite
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences all number
    2
    0
    2
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    4 / 220 (1.82%)
         occurrences all number
    0
    2
    4
    Molluscum contagiosum
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    7 / 44 (15.91%)
    7 / 132 (5.30%)
    3 / 220 (1.36%)
         occurrences all number
    8
    11
    4
    Otitis externa
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    0 / 220 (0.00%)
         occurrences all number
    0
    2
    0
    Otitis media acute
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 132 (1.52%)
    2 / 220 (0.91%)
         occurrences all number
    1
    2
    2
    Otitis media
         subjects affected / exposed
    3 / 44 (6.82%)
    20 / 132 (15.15%)
    27 / 220 (12.27%)
         occurrences all number
    3
    32
    38
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    1 / 220 (0.45%)
         occurrences all number
    0
    2
    1
    Pharyngitis
         subjects affected / exposed
    6 / 44 (13.64%)
    15 / 132 (11.36%)
    18 / 220 (8.18%)
         occurrences all number
    7
    18
    19
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 132 (1.52%)
    7 / 220 (3.18%)
         occurrences all number
    0
    2
    7
    Respiratory tract infection viral
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 132 (0.76%)
    3 / 220 (1.36%)
         occurrences all number
    4
    1
    5
    Respiratory tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 132 (0.76%)
    4 / 220 (1.82%)
         occurrences all number
    0
    1
    5
    Rhinitis
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 132 (2.27%)
    8 / 220 (3.64%)
         occurrences all number
    3
    4
    11
    Skin candida
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    0 / 220 (0.00%)
         occurrences all number
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    4 / 44 (9.09%)
    9 / 132 (6.82%)
    6 / 220 (2.73%)
         occurrences all number
    5
    9
    7
    Tracheitis
         subjects affected / exposed
    1 / 44 (2.27%)
    5 / 132 (3.79%)
    1 / 220 (0.45%)
         occurrences all number
    1
    6
    1
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 44 (13.64%)
    34 / 132 (25.76%)
    58 / 220 (26.36%)
         occurrences all number
    9
    61
    103
    Urinary tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 132 (2.27%)
    7 / 220 (3.18%)
         occurrences all number
    0
    3
    7
    Varicella
         subjects affected / exposed
    2 / 44 (4.55%)
    3 / 132 (2.27%)
    5 / 220 (2.27%)
         occurrences all number
    2
    3
    5
    Viral infection
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 132 (1.52%)
    3 / 220 (1.36%)
         occurrences all number
    1
    2
    3
    Viral pharyngitis
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 132 (0.76%)
    0 / 220 (0.00%)
         occurrences all number
    2
    1
    0
    Viral tonsillitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 132 (0.00%)
    2 / 220 (0.91%)
         occurrences all number
    1
    0
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    5 / 44 (11.36%)
    23 / 132 (17.42%)
    45 / 220 (20.45%)
         occurrences all number
    6
    32
    91
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 132 (1.52%)
    1 / 220 (0.45%)
         occurrences all number
    1
    4
    1
    Decreased appetite (loss of appetite)
    alternative assessment type: Systematic
         subjects affected / exposed
    22 / 44 (50.00%)
    50 / 132 (37.88%)
    142 / 220 (64.55%)
         occurrences all number
    35
    76
    250

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Feb 2015
    Updation of description of control vaccine (pediatric HAV vaccine) and removal of references to a specific brand of control vaccine (Havrix Junior), clinical experience section for bivalent rLP2086, background section to include current licensure status of Bexsero and Trumenba, clarification of administration site instructions, correction of typographical errors related to data monitoring comittee (blinded to unblinded).
    19 Apr 2016
    Updation of unblinding strategy based on the actual enrollment rate, required freezer temperature for storing serum samples, adverse event reporting section, clarification of the performance of primary analysis and timing of stages of the study, incorporation of updates from administrative change letters of the date 02 September 2015 and 12 November 2015, deletion of appendix detailing the enrollment plan.

    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.
    The data for the immunogenicity outcome measures at 6, 12, and 24 months after Vaccination 3 and 1 month after the Booster dose are not available due to lab delays. The results will be posted as soon as the data is available.
    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.

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