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    Clinical Trial Results:
    A Phase 3 Study to Assess the Persistence of hSBA Response up to 48 Months After Completion of a Primary Series of Bivalent rLP2086, and the Safety, Tolerability, and Immunogenicity of a Booster Dose of Bivalent rLP2086

    Summary
    EudraCT number
    2011-005697-31
    Trial protocol
    CZ   SE   DE   DK   FI   PL  
    Global end of trial date
    05 Jan 2018

    Results information
    Results version number
    v4(current)
    This version publication date
    30 Dec 2020
    First version publication date
    21 Jul 2018
    Other versions
    v1 , v2 , v3
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    B1971033
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01543087
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 1-800-718-1021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Jun 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Stage 1 • To describe the immunogenicity of bivalent recombinant lipoprotein 2086 vaccine (rLP2086) as determined by serum bactericidal assay using human complement (hSBA) titers to 4 primary test strains at approximately 6, 12, 18, 24, 36, and 48 months after the last dose (second or third dose) of bivalent rLP2086 or saline in the primary study. Booster Stage • To describe the immune response as measured by hSBA titers to 4 primary test strains 1 month following the last vaccination with bivalent rLP2086 in the primary study, before the booster vaccination, and 1 month, 12 months, and 26 months after a single booster dose of bivalent rLP2086. • To evaluate the safety profile of bivalent rLP2086 as measured by the incidence of local reactions, systemic events, adverse events (AEs), serious adverse events (SAEs), newly diagnosed chronic medical conditions (NDCMCs), medically attended events, and immediate AEs following a booster vaccination of bivalent rLP2086.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 Sep 2012
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    26 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czechia: 153
    Country: Number of subjects enrolled
    Denmark: 216
    Country: Number of subjects enrolled
    Finland: 40
    Country: Number of subjects enrolled
    Germany: 54
    Country: Number of subjects enrolled
    Sweden: 42
    Country: Number of subjects enrolled
    United States: 193
    Worldwide total number of subjects
    698
    EEA total number of subjects
    505
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    73
    Adolescents (12-17 years)
    468
    Adults (18-64 years)
    157
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Total 698 subjects enrolled in this extension study, who were enrolled in any 1 of the primary studies B1971010 (NCT01323270), B1971012 (NCT01299480), and B1971015 (NCT01461980).

    Pre-assignment
    Screening details
    This study consisted of 2 stages: Stage 1 and Booster stage. Only subjects from primary studies B1971010 and B1971012 who received bivalent rLP2086 in the primary study and completed Stage 1 in this study, were eligible to participate in the booster stage.

    Period 1
    Period 1 title
    Stage 1
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)
    Arm description
    Subjects received quadrivalent meningococcal polysaccharide conjugate (MCV4) tetanus + acellular pertussis (Tdap) +Saline at Month 0, Saline only at Month 2 and 6 schedule in primary study B1971015 and were followed up for 48 months during the stage 1 of this study.
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 micrograms (mcg) of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Arm description
    Subject who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study. Only subjects from B1971010 and B1971012 studies received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 4: rLP2086 (0-and 6-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 5: rLP2086 (0- and 2-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 6: rLP2086 (0- and 4-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Number of subjects in period 1
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Started
    70
    103
    277
    116
    86
    46
    Safety Population
    70
    101
    277
    116
    86
    46
    Completed
    56
    93
    237
    108
    83
    46
    Not completed
    14
    10
    40
    8
    3
    0
         Protocol deviation
    -
    3
    -
    -
    -
    -
         No longer meets eligibility criteria
    1
    -
    1
    2
    -
    -
         Other than specified
    5
    -
    9
    -
    -
    -
         No longer willing to participate
    5
    3
    18
    6
    3
    -
         Lost to follow-up
    3
    4
    12
    -
    -
    -
    Period 2
    Period 2 title
    Booster Stage
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 micrograms (mcg) of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Arm description
    Subject who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study. Only subjects from B1971010 and B1971012 studies received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 4: rLP2086 (0-and 6-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 5: rLP2086 (0- and 2-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Arm title
    Group 6: rLP2086 (0- and 4-Month Schedule)
    Arm description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Arm type
    Experimental

    Investigational medicinal product name
    Bivalent rLP2086
    Investigational medicinal product code
    PF-05212366
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 0.5 mL of bivalent rLP2086 injection into the deltoid muscle.

    Number of subjects in period 2 [1]
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Started
    60
    92
    64
    56
    32
    Vaccinated
    59
    92
    64
    54
    32
    Completed
    59
    91
    64
    54
    32
    Not completed
    1
    1
    0
    2
    0
         Withdrawal before booster vaccination
    1
    -
    -
    2
    -
         Lost to follow-up
    -
    1
    -
    -
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Only subjects from primary studies B1971010 and B1971012 who completed Stage 1, received bivalent rLP2086 in primary study and agreed to participate in booster stage, where included in this period

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subjects received quadrivalent meningococcal polysaccharide conjugate (MCV4) tetanus + acellular pertussis (Tdap) +Saline at Month 0, Saline only at Month 2 and 6 schedule in primary study B1971015 and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 micrograms (mcg) of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subject who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study. Only subjects from B1971010 and B1971012 studies received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 4: rLP2086 (0-and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 5: rLP2086 (0- and 2-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 6: rLP2086 (0- and 4-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Total
    Number of subjects
    70 103 277 116 86 46 698
    Age categorical
    Units: Subjects
    Age Continuous
    The age of subjects enrolled in B1971033 is the age of subjects at Stage 1 enrollment.
    Units: years
        arithmetic mean (standard deviation)
    11.7 ± 0.7 15.9 ± 2.2 14.3 ± 2.8 15.8 ± 2.1 16.1 ± 2.4 15.9 ± 2.1 -
    Sex: Female, Male
    Units: Subjects
        Female
    32 55 144 67 38 26 362
        Male
    38 48 133 49 48 20 336
    Race/Ethnicity, Customized
    Units: Subjects
        White
    59 103 256 115 85 46 664
        Black
    9 0 12 1 0 0 22
        Other
    2 0 8 0 1 0 11
        Asian
    0 0 1 0 0 0 1
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    16 0 25 1 2 0 44
        Not Hispanic or Latino
    54 103 252 115 84 46 654
        Unknown or Not Reported
    0 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subjects received quadrivalent meningococcal polysaccharide conjugate (MCV4) tetanus + acellular pertussis (Tdap) +Saline at Month 0, Saline only at Month 2 and 6 schedule in primary study B1971015 and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 micrograms (mcg) of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subject who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study. Only subjects from B1971010 and B1971012 studies received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 4: rLP2086 (0-and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 5: rLP2086 (0- and 2-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 6: rLP2086 (0- and 4-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.
    Reporting group title
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 micrograms (mcg) of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subject who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study. Only subjects from B1971010 and B1971012 studies received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 4: rLP2086 (0-and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 5: rLP2086 (0- and 2-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Reporting group title
    Group 6: rLP2086 (0- and 4-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study, and received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately at Month 48) in booster stage of study B1971033.

    Subject analysis set title
    Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

    Subject analysis set title
    Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033

    Subject analysis set title
    Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Subject analysis set type
    Modified intention-to-treat
    Subject analysis set description
    Subjects received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971015.

    Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations

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    End point title
    Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 6 (Visit 1) After Primary Vaccinations [1] [2]
    End point description
    For immunogenicity assessment, serum bactericidal assay using human complement (hSBA) was performed with 4 primary Neisseria meningitidis serogroup B (MnB) test strains. 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). Modified intent-to-treat (mITT) population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain. Subjects who received bivalent rLP2086 in primary study B1971012, were entered in this study at Month 12 (Visit 2). Hence, no subjects enrolled from primary study B1971012 had serology results at Month 6.
    End point type
    Primary
    End point timeframe
    Month 6 (Visit 1 of study B1971033)
    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.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    70
    40
    123
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 7, 37, 18)
    14.3 (0.4 to 57.9)
    86.5 (71.2 to 95.5)
    83.3 (58.6 to 96.4)
        PMB2001 (A56) (n= 6, 36, 18)
    16.7 (0.4 to 64.1)
    72.2 (54.8 to 85.8)
    88.9 (65.3 to 98.6)
        PMB2948 (B24) (n= 7, 38, 17)
    0.0 (0.0 to 41.0)
    36.8 (21.8 to 54.0)
    35.3 (14.2 to 61.7)
        PMB2707 (B44) (n= 7, 37, 16)
    0.0 (0.0 to 41.0)
    64.9 (47.5 to 79.8)
    56.3 (29.9 to 80.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations

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    End point title
    Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 12 (Visit 2) After Primary Vaccinations [3] [4]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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). mITT population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain.
    End point type
    Primary
    End point timeframe
    Month 12 (Visit 2 of study B1971033)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    70
    101
    116
    86
    46
    40
    114
    123
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 69, 99, 113, 84, 46, 39, 111, 122)
    29.0 (18.7 to 41.2)
    41.4 (31.6 to 51.8)
    36.3 (27.4 to 45.9)
    44.0 (33.2 to 55.3)
    41.3 (27.0 to 56.8)
    69.2 (52.4 to 83.0)
    45.0 (35.6 to 54.8)
    61.5 (52.2 to 70.1)
        PMB2001(A56)(n= 69, 98, 106, 84, 42, 39, 109, 111)
    17.4 (9.3 to 28.4)
    73.5 (63.6 to 81.9)
    60.4 (50.4 to 69.7)
    69.0 (58.0 to 78.7)
    71.4 (55.4 to 84.3)
    66.7 (49.8 to 80.9)
    76.1 (67.0 to 83.8)
    63.1 (53.4 to 72.0)
        PMB2948(B24)(n= 70, 98, 103, 82, 46, 40, 108, 121)
    1.4 (0.0 to 7.7)
    40.8 (31.0 to 51.2)
    36.9 (27.6 to 47.0)
    41.5 (30.7 to 52.9)
    37.0 (23.2 to 52.5)
    37.5 (22.7 to 54.2)
    49.1 (39.3 to 58.9)
    24.0 (16.7 to 32.6)
        PMB2707(B44)(n=70, 100, 115, 85, 45, 40, 111, 120)
    1.4 (0.0 to 7.7)
    24.0 (16.0 to 33.6)
    16.5 (10.3 to 24.6)
    21.2 (13.1 to 31.4)
    22.2 (11.2 to 37.1)
    47.5 (31.5 to 63.9)
    22.5 (15.1 to 31.4)
    32.5 (24.2 to 41.7)
    No statistical analyses for this end point

    Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations

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    End point title
    Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 18 (Visit 3) After Primary Vaccinations [5] [6]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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). mITT population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain.
    End point type
    Primary
    End point timeframe
    Month 18 (Visit 3 of study B1971033)
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    70
    101
    116
    86
    46
    40
    114
    123
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 69, 97, 111, 85, 45, 38, 112, 117)
    23.2 (13.9 to 34.9)
    37.1 (27.5 to 47.5)
    47.7 (38.2 to 57.4)
    47.1 (36.1 to 58.2)
    51.1 (35.8 to 66.3)
    57.9 (40.8 to 73.7)
    44.6 (35.2 to 54.3)
    51.3 (41.9 to 60.6)
        PMB2001(A56)(n= 67, 94, 102, 83, 43, 39, 106, 114)
    11.9 (5.3 to 22.2)
    64.9 (54.4 to 74.5)
    57.8 (47.7 to 67.6)
    62.7 (51.3 to 73.0)
    62.8 (46.7 to 77.0)
    56.4 (39.6 to 72.2)
    72.6 (63.1 to 80.9)
    53.5 (43.9 to 62.9)
        PMB2948(B24)(n= 69, 96, 105, 81, 44, 38, 109, 113)
    5.8 (1.6 to 14.2)
    45.8 (35.6 to 56.3)
    31.4 (22.7 to 41.2)
    39.5 (28.8 to 51.0)
    50.0 (34.6 to 65.4)
    39.5 (24.0 to 56.6)
    46.8 (37.2 to 56.6)
    23.9 (16.4 to 32.8)
        PMB2707(B44)(n= 69, 98, 113, 86, 46, 38, 110, 115)
    0.0 (0.0 to 5.2)
    26.5 (18.1 to 36.4)
    15.9 (9.7 to 24.0)
    24.4 (15.8 to 34.9)
    28.3 (16.0 to 43.5)
    31.6 (17.5 to 48.7)
    18.2 (11.5 to 26.7)
    29.6 (21.4 to 38.8)
    No statistical analyses for this end point

    Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations

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    End point title
    Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 24 (Visit 4) After Primary Vaccinations [7] [8]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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). mITT population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain.
    End point type
    Primary
    End point timeframe
    Month 24 (Visit 4 of study B1971033)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    70
    101
    116
    86
    46
    40
    114
    123
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 68, 98, 109, 84, 46, 38, 107, 115)
    17.6 (9.5 to 28.8)
    34.7 (25.4 to 45.0)
    42.2 (32.8 to 52.0)
    44.0 (33.2 to 55.3)
    39.1 (25.1 to 54.6)
    50.0 (33.4 to 66.6)
    40.2 (30.8 to 50.1)
    49.6 (40.1 to 59.0)
        PMB2001(A56)(n= 66, 91, 104, 80, 45, 38, 102, 110)
    3.0 (0.4 to 10.5)
    69.2 (58.7 to 78.5)
    53.8 (43.8 to 63.7)
    58.8 (47.2 to 69.6)
    60.0 (44.3 to 74.3)
    57.9 (40.8 to 73.7)
    68.6 (58.7 to 77.5)
    36.4 (27.4 to 46.1)
        PMB2948(B24)(n= 68, 93, 110, 83, 45, 38, 107, 112)
    4.4 (0.9 to 12.4)
    43.0 (32.8 to 53.7)
    31.8 (23.3 to 41.4)
    37.3 (27.0 to 48.7)
    51.1 (35.8 to 66.3)
    39.5 (24.0 to 56.6)
    43.0 (33.5 to 52.9)
    25.9 (18.1 to 35.0)
        PMB2707(B44)(n= 67, 97, 108, 83, 46, 39, 109, 114)
    3.0 (0.4 to 10.4)
    23.7 (15.7 to 33.4)
    15.7 (9.4 to 24.0)
    22.9 (14.4 to 33.4)
    28.3 (16.0 to 43.5)
    38.5 (23.4 to 55.4)
    18.3 (11.6 to 26.9)
    27.2 (19.3 to 36.3)
    No statistical analyses for this end point

    Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations

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    End point title
    Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 36 (Visit 5) After Primary Vaccinations [9] [10]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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). mITT population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain.
    End point type
    Primary
    End point timeframe
    Month 36 (Visit 5 of study B1971033)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    70
    101
    116
    86
    46
    40
    114
    123
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 58, 96, 108, 82, 44, 38, 102, 107)
    27.6 (16.7 to 40.9)
    41.7 (31.7 to 52.2)
    42.6 (33.1 to 52.5)
    42.7 (31.8 to 54.1)
    34.1 (20.5 to 49.9)
    60.5 (43.4 to 76.0)
    39.2 (29.7 to 49.4)
    49.5 (39.7 to 59.4)
        PMB2001 (A56) (n= 57, 94, 99, 81, 42, 37, 92, 103)
    7.0 (1.9 to 17.0)
    58.5 (47.9 to 68.6)
    58.6 (48.2 to 68.4)
    59.3 (47.8 to 70.1)
    50.0 (34.2 to 65.8)
    54.1 (36.9 to 70.5)
    67.4 (56.8 to 76.8)
    35.0 (25.8 to 45.0)
        PMB2948(B24)(n= 59, 93, 107, 81, 43, 36, 100, 103)
    3.4 (0.4 to 11.7)
    41.9 (31.8 to 52.6)
    33.6 (24.8 to 43.4)
    48.1 (36.9 to 59.5)
    41.9 (27.0 to 57.9)
    38.9 (23.1 to 56.5)
    42.0 (32.2 to 52.3)
    30.1 (21.5 to 39.9)
        PMB2707(B44)(n= 59, 97, 109, 83, 44, 39, 103, 103)
    1.7 (0.0 to 9.1)
    21.6 (13.9 to 31.2)
    20.2 (13.1 to 28.9)
    21.7 (13.4 to 32.1)
    18.2 (8.2 to 32.7)
    33.3 (19.1 to 50.2)
    16.5 (9.9 to 25.1)
    24.3 (16.4 to 33.7)
    No statistical analyses for this end point

    Primary: Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations

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    End point title
    Percentage of Subjects in Stage 1 Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains at Month 48 (Visit 6) After Primary Vaccinations [11] [12]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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). mITT population included subjects who had at least 1 valid and determinate assay result in Stage 1 of Study B1971033. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain.
    End point type
    Primary
    End point timeframe
    Month 48 (Visit 6 of study B1971033)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3c: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    70
    101
    116
    86
    46
    40
    114
    123
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 55, 90, 101, 81, 46, 35, 100, 101)
    16.4 (7.8 to 28.8)
    41.1 (30.8 to 52.0)
    39.6 (30.0 to 49.8)
    45.7 (34.6 to 57.1)
    41.3 (27.0 to 56.8)
    51.4 (34.0 to 68.6)
    43.0 (33.1 to 53.3)
    34.7 (25.5 to 44.8)
        PMB2001 (A56) (n= 51, 85, 99, 75, 46, 33, 99, 94)
    2.0 (0.0 to 10.4)
    47.1 (36.1 to 58.2)
    57.6 (47.2 to 67.5)
    61.3 (49.4 to 72.4)
    47.8 (32.9 to 63.1)
    42.4 (25.5 to 60.8)
    58.6 (48.2 to 68.4)
    30.9 (21.7 to 41.2)
        PMB2948(B24)(n= 56, 90, 105, 82, 45, 34, 98, 101)
    7.1 (2.0 to 17.3)
    41.1 (30.8 to 52.0)
    30.5 (21.9 to 40.2)
    45.1 (34.1 to 56.5)
    42.2 (27.7 to 57.8)
    50.0 (32.4 to 67.6)
    40.8 (31.0 to 51.2)
    23.8 (15.9 to 33.3)
        PMB2707(B44)(n= 56, 92, 106, 82, 46, 34, 100, 100)
    3.6 (0.4 to 12.3)
    20.7 (12.9 to 30.4)
    18.9 (11.9 to 27.6)
    24.4 (15.6 to 35.1)
    23.9 (12.6 to 38.8)
    41.2 (24.6 to 59.3)
    18.0 (11.0 to 26.9)
    23.0 (15.2 to 32.5)
    No statistical analyses for this end point

    Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study

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    End point title
    Percentage of Booster Stage Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After Last Vaccination in Primary Study [13]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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 population included all eligible subjects who received scheduled investigational products, had received no prohibited vaccines or treatment, 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 with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage.
    End point type
    Primary
    End point timeframe
    1 month after last vaccination in primary study
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    59
    62
    54
    32
    31
    58
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 59, 61, 54, 32, 31, 57)
    89.8 (79.2 to 96.2)
    98.4 (91.2 to 100.0)
    77.8 (64.4 to 88.0)
    84.4 (67.2 to 94.7)
    100.0 (88.8 to 100.0)
    91.2 (80.7 to 97.1)
        PMB2001 (A56) (n= 58, 62, 54, 32, 31, 57)
    100.0 (93.8 to 100.0)
    98.4 (91.3 to 100.0)
    100.0 (93.4 to 100.0)
    96.9 (83.8 to 99.9)
    100.0 (88.8 to 100.0)
    98.2 (90.6 to 100.0)
        PMB2948 (B24) (n= 59, 60, 52, 29, 31, 58)
    88.1 (77.1 to 95.1)
    85.0 (73.4 to 92.9)
    71.2 (56.9 to 82.9)
    79.3 (60.3 to 92.0)
    93.5 (78.6 to 99.2)
    91.4 (81.0 to 97.1)
        PMB2707 (B44) (n= 58, 60, 52, 32, 31, 57)
    86.2 (74.6 to 93.9)
    81.7 (69.6 to 90.5)
    73.1 (59.0 to 84.4)
    87.5 (71.0 to 96.5)
    96.8 (83.3 to 99.9)
    89.5 (78.5 to 96.0)
    No statistical analyses for this end point

    Primary: Percentage of Booster Stage Subjects Achieving hSBA Titer Level >= Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6])

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    End point title
    Percentage of Booster Stage Subjects Achieving hSBA Titer Level >= Lower Limit of Quantitation for Each of the 4 Primary Strains Before Booster Vaccination (48 Months After Last Vaccination in Primary Study [Visit 6]) [14]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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 population included all eligible subjects who received scheduled investigational products, had received no prohibited vaccines or treatment, 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 with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage.
    End point type
    Primary
    End point timeframe
    Visit 6 of study B1971033 (48 months after last vaccination in primary study)
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    59
    62
    54
    32
    31
    58
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 59, 61, 54, 31, 31, 57)
    49.2 (35.9 to 62.5)
    55.7 (42.4 to 68.5)
    57.4 (43.2 to 70.8)
    48.4 (30.2 to 66.9)
    48.4 (30.2 to 66.9)
    56.1 (42.4 to 69.3)
        PMB2001 (A56) (n= 53, 62, 52, 30, 29, 55)
    43.4 (29.8 to 57.7)
    43.5 (31.0 to 56.7)
    51.9 (37.6 to 66.0)
    43.3 (25.5 to 62.6)
    41.4 (23.5 to 61.1)
    56.4 (42.3 to 69.7)
        PMB2948 (B24) (n= 59, 62, 54, 31, 30, 57)
    40.7 (28.1 to 54.3)
    40.3 (28.1 to 53.6)
    46.3 (32.6 to 60.4)
    45.2 (27.3 to 64.0)
    46.7 (28.3 to 65.7)
    49.1 (35.6 to 62.7)
        PMB2707 (B44) (n= 57, 62, 53, 32, 30, 57)
    36.8 (24.4 to 50.7)
    12.9 (5.7 to 23.9)
    37.7 (24.8 to 52.1)
    34.4 (18.6 to 53.2)
    33.3 (17.3 to 52.8)
    35.1 (22.9 to 48.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8)

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    End point title
    Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 1 Month After the Booster Vaccination (Visit 8) [15]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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 population included all eligible subjects who received scheduled investigational products,had received no prohibited vaccines or treatment, 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 with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage.
    End point type
    Primary
    End point timeframe
    Visit 8 (1 month following the booster vaccination on Month 49)
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    59
    62
    54
    32
    31
    58
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 59, 60, 53, 32, 31, 58)
    100.0 (93.9 to 100.0)
    96.7 (88.5 to 99.6)
    98.1 (89.9 to 100.0)
    100.0 (89.1 to 100.0)
    96.8 (83.3 to 99.9)
    100.0 (93.8 to 100.0)
        PMB2001 (A56) (n= 57, 62, 51, 32, 30, 56)
    100.0 (93.7 to 100.0)
    98.4 (91.3 to 100.0)
    100.0 (93.0 to 100.0)
    100.0 (89.1 to 100.0)
    100.0 (88.4 to 100.0)
    100.0 (93.6 to 100.0)
        PMB2948 (B24) (n= 58, 62, 54, 32, 31, 57)
    100.0 (93.8 to 100.0)
    96.8 (88.8 to 99.6)
    94.4 (84.6 to 98.8)
    100.0 (89.1 to 100.0)
    96.8 (83.3 to 99.9)
    100.0 (93.7 to 100.0)
        PMB2707 (B44) (n= 59, 61, 53, 32, 31, 58)
    100.0 (93.9 to 100.0)
    93.4 (84.1 to 98.2)
    100.0 (93.3 to 100.0)
    100.0 (89.1 to 100.0)
    100.0 (88.8 to 100.0)
    100.0 (93.8 to 100.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10)

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    End point title
    Percentage of Subjects Achieving hSBATiter Level Greater Than or Equal to (>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 12 Months After the Booster Vaccination(Visit 10) [16]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 primary MnB test strains. 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 population included all eligible subjects who received scheduled investigational products, had received no prohibited vaccines or treatment, 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 with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage.
    End point type
    Primary
    End point timeframe
    Visit 10 (12 months following the booster vaccination on Month 60)
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule) Group 3a: rLP2086 (0-, 2-, and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    59
    62
    54
    32
    31
    58
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 58, 60, 51, 31, 28, 54)
    74.1 (61.0 to 84.7)
    80.0 (67.7 to 89.2)
    82.4 (69.1 to 91.6)
    96.8 (83.3 to 99.9)
    89.3 (71.8 to 97.7)
    77.8 (64.4 to 88.0)
        PMB2001 (A56) (n= 55, 59, 50, 32, 24, 55)
    90.9 (80.0 to 97.0)
    81.4 (69.1 to 90.3)
    74.0 (59.7 to 85.4)
    100.0 (89.1 to 100.0)
    87.5 (67.6 to 97.3)
    89.1 (77.8 to 95.9)
        PMB2948 (B24) (n= 58, 62, 49, 32, 30, 54)
    65.5 (51.9 to 77.5)
    77.4 (65.0 to 87.1)
    65.3 (50.4 to 78.3)
    84.4 (67.2 to 94.7)
    66.7 (47.2 to 82.7)
    74.1 (60.3 to 85.0)
        PMB2707 (B44) (n= 56, 61, 52, 30, 30, 53)
    75.0 (61.6 to 85.6)
    59.0 (45.7 to 71.4)
    78.8 (65.3 to 88.9)
    93.3 (77.9 to 99.2)
    76.7 (57.7 to 90.1)
    81.1 (68.0 to 90.6)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11)

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    End point title
    Percentage of Subjects Achieving hSBA Titer Level Greater Than or Equal to(>=) Lower Limit of Quantitation (LLOQ) for Each of the 4 Primary Strains 26 Months After the Booster Vaccination(Visit 11) [17]
    End point description
    For immunogenicity assessment, hSBA was performed with 4 MnB test strains. 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 population set was used in the analysis. Here, ’n’ signifies number of subjects with valid and determinate hSBA titers for the given strain. Subjects of Group 3c (subjects from primary study B1971015) were not continued in booster stage. Subjects who received bivalent rLP2086 in primary study B1971010 were not analysed for this endpoint. Only subjects who received bivalent rLP2086 in primary study B1971012 on a 0-, 2-, and 6-month or a 0- and 6-month vaccination schedule were eligible to be followed for 26 months after booster vaccination.
    End point type
    Primary
    End point timeframe
    Visit 11 (26 months following the booster vaccination on Month 74)
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 4: rLP2086 (0-and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    62
    58
    Units: percentage of subjects
    number (confidence interval 95%)
        PMB80 (A22) (n= 42, 34)
    61.9 (45.6 to 76.4)
    73.5 (55.6 to 87.1)
        PMB2001 (A56) (n= 40, 29)
    57.5 (40.9 to 73.0)
    82.8 (64.2 to 94.2)
        PMB2948 (B24) (n= 42, 33)
    59.5 (43.3 to 74.4)
    78.8 (61.1 to 91.0)
        PMB2707 (B44) (n= 43, 33)
    62.8 (46.7 to 77.0)
    66.7 (48.2 to 82.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination

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    End point title
    Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination [18]
    End point description
    Local reactions were collected by using an e-diary and included pain at injection site, redness and swelling. Redness and swelling were graded as: none (0-2.0 centimetre [cm]), mild (2.5-5.0 cm), moderate (greater than [>] 5.0-10.0 cm) and severe (>10.0 cm). Pain was graded as: mild (does not interfere with activity), moderate (Interferes with activity) and severe (prevents daily activity). Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    Within 7 days after booster vaccination on Month 48
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
    number (confidence interval 95%)
        Pain at injection site:Any
    91.5 (81.3 to 97.2)
    93.5 (86.3 to 97.6)
    89.1 (78.8 to 95.5)
    88.9 (77.4 to 95.8)
    84.4 (67.2 to 94.7)
        Pain at injection site:Mild
    37.3 (25.0 to 50.9)
    29.3 (20.3 to 39.8)
    28.1 (17.6 to 40.8)
    35.2 (22.7 to 49.4)
    25.0 (11.5 to 43.4)
        Pain at injection site:Moderate
    40.7 (28.1 to 54.3)
    54.3 (43.6 to 64.8)
    51.6 (38.7 to 64.2)
    44.4 (30.9 to 58.6)
    46.9 (29.1 to 65.3)
        Pain at injection site:Severe
    13.6 (6.0 to 25.0)
    9.8 (4.6 to 17.8)
    9.4 (3.5 to 19.3)
    9.3 (3.1 to 20.3)
    12.5 (3.5 to 29.0)
        Redness:Any
    20.3 (11.0 to 32.8)
    20.7 (12.9 to 30.4)
    20.3 (11.3 to 32.2)
    27.8 (16.5 to 41.6)
    6.3 (0.8 to 20.8)
        Redness:Mild
    6.8 (1.9 to 16.5)
    5.4 (1.8 to 12.2)
    10.9 (4.5 to 21.2)
    5.6 (1.2 to 15.4)
    3.1 (0.1 to 16.2)
        Redness:Moderate
    11.9 (4.9 to 22.9)
    10.9 (5.3 to 19.1)
    7.8 (2.6 to 17.3)
    16.7 (7.9 to 29.3)
    3.1 (0.1 to 16.2)
        Redness:Severe
    1.7 (0.0 to 9.1)
    4.3 (1.2 to 10.8)
    1.6 (0.0 to 8.4)
    5.6 (1.2 to 15.4)
    0.0 (0.0 to 10.9)
        Swelling:Any
    18.6 (9.7 to 30.9)
    20.7 (12.9 to 30.4)
    17.2 (8.9 to 28.7)
    14.8 (6.6 to 27.1)
    9.4 (2.0 to 25.0)
        Swelling:Mild
    11.9 (4.9 to 22.9)
    8.7 (3.8 to 16.4)
    10.9 (4.5 to 21.2)
    3.7 (0.5 to 12.7)
    9.4 (2.0 to 25.0)
        Swelling:Moderate
    6.8 (1.9 to 16.5)
    10.9 (5.3 to 19.1)
    6.3 (1.7 to 15.2)
    11.1 (4.2 to 22.6)
    0.0 (0.0 to 10.9)
        Swelling:Severe
    0.0 (0.0 to 6.1)
    1.1 (0.0 to 5.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
    No statistical analyses for this end point

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

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    End point title
    Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination [19]
    End point description
    Systemic reactions included: fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at the injection site and joint pain, all other systemic reactions were recorded by using an e-diary. Fever was categorized as: 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and > 40.0 degree C. Vomiting was graded as: mild (1 to 2 times in 24 hours [hrs]), moderate (>2 times in 24 hrs) and severe (requires intravenous [IV] hydration); Diarrhea was graded as: mild (2 to 3 loose stools in 24 hrs), moderate (4 to 5 loose stools in 24 hrs) and severe (6 or more loose stools in 24 hrs); Headache, fatigue, chills, muscle pain and joint pain was graded as: mild (does not interfere with daily activities), moderate (some interference with activity) and severe (prevents daily routine activity). Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    Within 7 days after booster vaccination on Month 48
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
    number (confidence interval 95%)
        Fever >=38 degrees C
    5.1 (1.1 to 14.1)
    1.1 (0.0 to 5.9)
    4.7 (1.0 to 13.1)
    1.9 (0.0 to 9.9)
    3.1 (0.1 to 16.2)
        Fever 38.0 to <38.5 degrees C
    5.1 (1.1 to 14.1)
    1.1 (0.0 to 5.9)
    3.1 (0.4 to 10.8)
    0.0 (0.0 to 6.6)
    3.1 (0.1 to 16.2)
        Fever 38.5 to <39.0 degrees C
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    1.6 (0.0 to 8.4)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        Fever 39.0 to 40.0 degrees C
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Fever >40.0 degrees C
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Vomiting:Any
    1.7 (0.0 to 9.1)
    3.3 (0.7 to 9.2)
    3.1 (0.4 to 10.8)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        Vomiting:Mild
    1.7 (0.0 to 9.1)
    3.3 (0.7 to 9.2)
    1.6 (0.0 to 8.4)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        Vomiting:Moderate
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    1.6 (0.0 to 8.4)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Vomiting:Severe
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Diarrhea:Any
    10.2 (3.8 to 20.8)
    13.0 (6.9 to 21.7)
    4.7 (1.0 to 13.1)
    5.6 (1.2 to 15.4)
    18.8 (7.2 to 36.4)
        Diarrhea:Mild
    8.5 (2.8 to 18.7)
    12.0 (6.1 to 20.4)
    3.1 (0.4 to 10.8)
    5.6 (1.2 to 15.4)
    18.8 (7.2 to 36.4)
        Diarrhea:Moderate
    1.7 (0.0 to 9.1)
    1.1 (0.0 to 5.9)
    1.6 (0.0 to 8.4)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Diarrhea:Severe
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Headache:Any
    50.8 (37.5 to 64.1)
    47.8 (37.3 to 58.5)
    56.3 (43.3 to 68.6)
    48.1 (34.3 to 62.2)
    37.5 (21.1 to 56.3)
        Headache:Mild
    30.5 (19.2 to 43.9)
    28.3 (19.4 to 38.6)
    35.9 (24.3 to 48.9)
    22.2 (12.0 to 35.6)
    25.0 (11.5 to 43.4)
        Headache:Moderate
    20.3 (11.0 to 32.8)
    18.5 (11.1 to 27.9)
    20.3 (11.3 to 32.2)
    25.9 (15.0 to 39.7)
    12.5 (3.5 to 29.0)
        Headache:Severe
    0.0 (0.0 to 6.1)
    1.1 (0.0 to 5.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        Fatigue:Any
    62.7 (49.1 to 75.0)
    60.9 (50.1 to 70.9)
    62.5 (49.5 to 74.3)
    51.9 (37.8 to 65.7)
    65.6 (46.8 to 81.4)
        Fatigue:Mild
    27.1 (16.4 to 40.3)
    27.2 (18.4 to 37.4)
    35.9 (24.3 to 48.9)
    24.1 (13.5 to 37.6)
    31.3 (16.1 to 50.0)
        Fatigue:Moderate
    32.2 (20.6 to 45.6)
    31.5 (22.2 to 42.0)
    23.4 (13.8 to 35.7)
    24.1 (13.5 to 37.6)
    31.3 (16.1 to 50.0)
        Fatigue:Severe
    3.4 (0.4 to 11.7)
    2.2 (0.3 to 7.6)
    3.1 (0.4 to 10.8)
    3.7 (0.5 to 12.7)
    3.1 (0.1 to 16.2)
        Chills:Any
    23.7 (13.6 to 36.6)
    31.5 (22.2 to 42.0)
    20.3 (11.3 to 32.2)
    18.5 (9.3 to 31.4)
    28.1 (13.7 to 46.7)
        Chills:Mild
    13.6 (6.0 to 25.0)
    20.7 (12.9 to 30.4)
    12.5 (5.6 to 23.2)
    9.3 (3.1 to 20.3)
    18.8 (7.2 to 36.4)
        Chills:Moderate
    10.2 (3.8 to 20.8)
    9.8 (4.6 to 17.8)
    7.8 (2.6 to 17.3)
    7.4 (2.1 to 17.9)
    9.4 (2.0 to 25.0)
        Chills:Severe
    0.0 (0.0 to 6.1)
    1.1 (0.0 to 5.9)
    0.0 (0.0 to 5.6)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        Muscle pain:Any
    22.0 (12.3 to 34.7)
    29.3 (20.3 to 39.8)
    18.8 (10.1 to 30.5)
    24.1 (13.5 to 37.6)
    15.6 (5.3 to 32.8)
        Muscle pain: Mild
    16.9 (8.4 to 29.0)
    15.2 (8.6 to 24.2)
    7.8 (2.6 to 17.3)
    14.8 (6.6 to 27.1)
    6.3 (0.8 to 20.8)
        Muscle pain:Moderate
    5.1 (1.1 to 14.1)
    13.0 (6.9 to 21.7)
    7.8 (2.6 to 17.3)
    5.6 (1.2 to 15.4)
    9.4 (2.0 to 25.0)
        Muscle pain:Severe
    0.0 (0.0 to 6.1)
    1.1 (0.0 to 5.9)
    3.1 (0.4 to 10.8)
    3.7 (0.5 to 12.7)
    0.0 (0.0 to 10.9)
        Joint pain:Any
    11.9 (4.9 to 22.9)
    16.3 (9.4 to 25.5)
    14.1 (6.6 to 25.0)
    18.5 (9.3 to 31.4)
    21.9 (9.3 to 40.0)
        Joint pain:Mild
    8.5 (2.8 to 18.7)
    9.8 (4.6 to 17.8)
    7.8 (2.6 to 17.3)
    7.4 (2.1 to 17.9)
    12.5 (3.5 to 29.0)
        Joint pain:Moderate
    3.4 (0.4 to 11.7)
    6.5 (2.4 to 13.7)
    4.7 (1.0 to 13.1)
    9.3 (3.1 to 20.3)
    9.4 (2.0 to 25.0)
        Joint pain:Severe
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    1.6 (0.0 to 8.4)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        Use of antipyretic medication
    10.2 (3.8 to 20.8)
    14.1 (7.7 to 23.0)
    7.8 (2.6 to 17.3)
    13.0 (5.4 to 24.9)
    6.3 (0.8 to 20.8)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8)

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    End point title
    Percentage of Subjects With at Least 1 Adverse Event (AE), Serious Adverse Event (SAE), Newly Diagnosed Chronic Medical Condition (NDCMC) and Medically Attended Adverse Event (MAE) From Booster Vaccination Phase (Visit 7 to Visit 8) [20]
    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. AEs included both non-serious AEs and SAEs. An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. An MAE was defined as a non-serious AE that resulted in an evaluation at a medical facility. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    From Visit 7 (Month 48) to Visit 8 (Month 49) in Booster stage
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
    number (confidence interval 95%)
        AE
    6.8 (1.9 to 16.5)
    8.7 (3.8 to 16.4)
    12.5 (5.6 to 23.2)
    3.7 (0.5 to 12.7)
    12.5 (3.5 to 29.0)
        SAE
    0.0 (0.0 to 6.1)
    1.1 (0.0 to 5.9)
    0.0 (0.0 to 5.6)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        NDCMC
    0.0 (0.0 to 6.1)
    0.0 (0.0 to 3.9)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        MAE
    5.1 (1.1 to 14.1)
    4.3 (1.2 to 10.8)
    4.7 (1.0 to 13.1)
    0.0 (0.0 to 6.6)
    3.1 (0.1 to 16.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9)

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    End point title
    Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Follow-Up Phase (Visit 8 to Visit 9) [21]
    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. An MAE was defined as a non-serious AE (AE other than SAE) that resulted in an evaluation at a medical facility. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    Visit 8 (Month 49) to Visit 9 (Month 54) in Booster stage
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
    number (confidence interval 95%)
        SAE
    1.7 (0.0 to 9.1)
    0.0 (0.0 to 3.9)
    3.1 (0.4 to 10.8)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
        MAE
    28.8 (17.8 to 42.1)
    12.0 (6.1 to 20.4)
    10.9 (4.5 to 21.2)
    11.1 (4.2 to 22.6)
    21.9 (9.3 to 40.0)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9)

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    End point title
    Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 to Visit 9) [22]
    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. An MAE was defined as a non-serious AE (AE other than SAE) that resulted in an evaluation at a medical facility. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    From Visit 7 (time of booster vaccination, Month 48) to Visit 9 (6 months after booster vaccination, Month 54)
    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 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
    number (confidence interval 95%)
        SAE
    1.7 (0.0 to 9.1)
    1.1 (0.0 to 5.9)
    3.1 (0.4 to 10.8)
    1.9 (0.0 to 9.9)
    0.0 (0.0 to 10.9)
        MAE
    32.2 (20.6 to 45.6)
    15.2 (8.6 to 24.2)
    15.6 (7.8 to 26.9)
    11.1 (4.2 to 22.6)
    25.0 (11.5 to 43.4)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1)

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    End point title
    Percentage of Subjects With Newly Diagnosed Chronic Medical Condition;(NDCMC) From the 6-Month Safety Telephone call in the Primary Study Through 48 Months After the Last Dose in the Primary Study (Visit 6 in Stage 1) [23]
    End point description
    An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Stage 1 safety population included all subjects who had at least 1 blood draw in the study.
    End point type
    Primary
    End point timeframe
    Visit 1 of B1971033 (6-month safety telephone call after last dose in primary study) to Visit 6 of B1971033 (6 months after last primary dose to 48 months after last primary dose in primary study)
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 1:MCV4+Tdap+Saline (0-, 2-, and 6-Month Schedule) Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    70
    101
    277
    116
    86
    46
    Units: percentage of subjects
        number (confidence interval 95%)
    5.7 (1.6 to 14.0)
    5.0 (1.6 to 11.2)
    2.2 (0.8 to 4.7)
    2.6 (0.5 to 7.4)
    2.3 (0.3 to 8.1)
    2.2 (0.1 to 11.5)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10)

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    End point title
    Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 12 Months After Booster Vaccination (Visit 8 to Visit 10) [24]
    End point description
    An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    From Visit 8 (1 month after booster vaccination, Month 49) to Visit 10 (12 months after booster vaccination, Month 60)
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    1.7 (0.0 to 9.1)
    2.2 (0.3 to 7.6)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10)

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    End point title
    Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Stage Vaccination Through 12 Months After Booster Vaccination (Visit 7 to Visit 10) [25]
    End point description
    An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    From Visit 7 (time of booster vaccination, Month 48) to Visit 10 (12 months after booster vaccination, Month 60)
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    1.7 (0.0 to 9.1)
    2.2 (0.3 to 7.6)
    0.0 (0.0 to 5.6)
    0.0 (0.0 to 6.6)
    0.0 (0.0 to 10.9)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11)

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    End point title
    Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From 1 Month After Booster Vaccination Through 26 Months After Booster Vaccination (Visit 8 to Visit 11) [26]
    End point description
    An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available. Here, “Overall number of subjects analyzed" signifies those subjects who were evaluable for this endpoint. Subjects who received bivalent rLP2086 in primary study B1971012 on a 0-, 2-, and 6-month or a 0- and 6-month vaccination schedule were eligible to be follow up for 26 months after booster vaccination.
    End point type
    Primary
    End point timeframe
    From Visit 8 (1 month after booster vaccination, Month 49) to Visit 11 (26 months after booster vaccination, Month 74)
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 4: rLP2086 (0-and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    49
    37
    Units: percentage of subjects
        number (confidence interval 95%)
    0.0 (0.0 to 7.3)
    5.4 (0.7 to 18.2)
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11)

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    End point title
    Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Booster Vaccine Through 26 Months After Booster Vaccination (Visit 7 to Visit 11) [27]
    End point description
    An NDCMC was defined as a disease or medical condition, that was not identified previously and that was expected to be persistent or otherwise long-lasting in its effects. The investigator determined if the AE was an NDCMC. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available. Subjects who received bivalent rLP2086 in primary study B1971012 on a 0-, 2-, and 6-month or a 0- and 6-month vaccination schedule were eligible to be follow up for 26 months after booster vaccination. Here, “Overall number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    From Visit 7 (time of booster vaccination, Month 48) to Visit 11 (26 months after booster vaccination, Month 74)
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 4: rLP2086 (0-and 6-Month Schedule) Group 3b: rLP2086 (0-, 2-, and 6-Month Schedule)
    Number of subjects analysed
    49
    37
    Units: percentage of subjects
        number (confidence interval 95%)
    0.0 (0.0 to 7.3)
    5.4 (0.7 to 18.2)
    No statistical analyses for this end point

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

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    End point title
    Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination [28]
    End point description
    Immediate AE was defined as AEs occurring within the first 30 minutes after investigational product administration. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available.
    End point type
    Primary
    End point timeframe
    within 30 minutes after Booster Vaccination in Month 48
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    59
    92
    64
    54
    32
    Units: percentage of subjects
        number (confidence interval 95%)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    0.0 (0.0 to 0.0)
    No statistical analyses for this end point

    Primary: Number of Days Subjects Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9)

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    End point title
    Number of Days Subjects Missed Work or School Due to AE From Booster Vaccination Through 6 Months After Booster Vaccination (Visit 7 Through Visit 9) [29]
    End point description
    An AE was any untoward medical occurrence in a subject who received investigational product without regard to possibility of causal relationship. Number of days subjects missed work or school due to AE occurred following booster vaccination were reported here. Booster stage safety population included all subjects who had received the booster vaccination (Bivalent rLP2086 ) and for whom safety data was available. Here, “Overall number of subjects analyzed" signifies those subjects who were evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    From Visit 7 (time of booster vaccination, Month 48) Through Visit 9 (6 months after booster vaccination, Month 54)
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analysed for this endpoint.
    End point values
    Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Group 4: rLP2086 (0-and 6-Month Schedule) Group 5: rLP2086 (0- and 2-Month Schedule) Group 6: rLP2086 (0- and 4-Month Schedule)
    Number of subjects analysed
    12
    8
    8
    3
    6
    Units: days
        arithmetic mean (standard deviation)
    17.5 ± 28.14
    12.4 ± 9.72
    10.1 ± 9.1
    3.0 ± 2.65
    4.8 ± 2.56
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs and Non SAEs: Visit 7 (Booster vaccination, Month 48) to Visit 11 (Month 74) [26 months]. Local reactions and systemic events: Recorded by subjects in e-diary from Day 1 to Day 7 after booster vaccination in Month 48.
    Adverse event reporting additional description
    AEs were reported for those subjects who had received the booster vaccination (Bivalent rLP2086) and for whom safety information was available for disclosure.SAEs were not collected for stage 1 of the study.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Stage 2, Group2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

    Reporting group title
    Stage 2, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

    Reporting group title
    Stage 2, Group 4: rLP2086 (0-and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

    Reporting group title
    Stage 2, Group 5: rLP2086 (0- and 2-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

    Reporting group title
    Stage 2, Group 6: rLP2086 (0- and 4-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of study B1971033.

    Reporting group title
    Stage 1, Group 1:MCV4+Tdap+Saline (0-, 2-, 6-Month Schedule)
    Reporting group description
    Subjects received MCV4+Tdap+Saline at Month 0, Saline only at Month 2 and 6 schedule in primary study B1971015 and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Stage 1, Group 2: rLP2086 (0-, 1-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 1-, and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Stage 1, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0-, 2-, and 6-month schedule in primary study B1971010, B1971012 and B1971015 were included in this group, and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Stage 1, Group 4: rLP2086 (0-and 6-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 6-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Stage 1, Group 5: rLP2086 (0- and 2-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 2-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

    Reporting group title
    Stage 1, Group 6: rLP2086 (0- and 4-Month Schedule)
    Reporting group description
    Subjects who received bivalent rLP2086 vaccine on 0- and 4-month schedule in primary study B1971012 and were followed up for 48 months during the stage 1 of this study.

    Serious adverse events
    Stage 2, Group2: rLP2086 (0-, 1-, and 6-Month Schedule) Stage 2, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Stage 2, Group 4: rLP2086 (0-and 6-Month Schedule) Stage 2, Group 5: rLP2086 (0- and 2-Month Schedule) Stage 2, Group 6: rLP2086 (0- and 4-Month Schedule) Stage 1, Group 1:MCV4+Tdap+Saline (0-, 2-, 6-Month Schedule) Stage 1, Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Stage 1, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Stage 1, Group 4: rLP2086 (0-and 6-Month Schedule) Stage 1, Group 5: rLP2086 (0- and 2-Month Schedule) Stage 1, Group 6: rLP2086 (0- and 4-Month Schedule)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    2 / 64 (3.13%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Meniscus injury
    Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Influenza like illness
    Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
    Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
    Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pyelonephritis
    Additional description: SAEs were not collected for stage 1 of the study, hence actual population exposed is "0". Current presentation is a resolution of database limitation.
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    Stage 2, Group2: rLP2086 (0-, 1-, and 6-Month Schedule) Stage 2, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Stage 2, Group 4: rLP2086 (0-and 6-Month Schedule) Stage 2, Group 5: rLP2086 (0- and 2-Month Schedule) Stage 2, Group 6: rLP2086 (0- and 4-Month Schedule) Stage 1, Group 1:MCV4+Tdap+Saline (0-, 2-, 6-Month Schedule) Stage 1, Group 2: rLP2086 (0-, 1-, and 6-Month Schedule) Stage 1, Group 3: rLP2086 (0-, 2-, and 6-Month Schedule) Stage 1, Group 4: rLP2086 (0-and 6-Month Schedule) Stage 1, Group 5: rLP2086 (0- and 2-Month Schedule) Stage 1, Group 6: rLP2086 (0- and 4-Month Schedule)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    56 / 59 (94.92%)
    90 / 92 (97.83%)
    62 / 64 (96.88%)
    53 / 54 (98.15%)
    31 / 32 (96.88%)
    4 / 70 (5.71%)
    0 / 101 (0.00%)
    1 / 277 (0.36%)
    0 / 116 (0.00%)
    2 / 86 (2.33%)
    1 / 46 (2.17%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Immune system disorders
    Mite allergy
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    1 / 86 (1.16%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Withdrawal syndrome
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Chills
    alternative assessment type: Systematic
         subjects affected / exposed
    14 / 59 (23.73%)
    29 / 92 (31.52%)
    13 / 64 (20.31%)
    10 / 54 (18.52%)
    9 / 32 (28.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    14
    29
    13
    10
    9
    0
    0
    0
    0
    0
    0
    Fatigue
    alternative assessment type: Systematic
         subjects affected / exposed
    37 / 59 (62.71%)
    56 / 92 (60.87%)
    40 / 64 (62.50%)
    28 / 54 (51.85%)
    21 / 32 (65.63%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    37
    56
    40
    28
    21
    0
    0
    0
    0
    0
    0
    Injection site erythema (redness)
    alternative assessment type: Systematic
         subjects affected / exposed
    12 / 59 (20.34%)
    19 / 92 (20.65%)
    13 / 64 (20.31%)
    15 / 54 (27.78%)
    2 / 32 (6.25%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    12
    19
    13
    15
    2
    0
    0
    0
    0
    0
    0
    Injection site pain (tenderness at injection site)
    alternative assessment type: Systematic
         subjects affected / exposed
    54 / 59 (91.53%)
    86 / 92 (93.48%)
    57 / 64 (89.06%)
    48 / 54 (88.89%)
    27 / 32 (84.38%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    54
    86
    57
    48
    27
    0
    0
    0
    0
    0
    0
    Injection site swelling (swelling)
    alternative assessment type: Systematic
         subjects affected / exposed
    11 / 59 (18.64%)
    19 / 92 (20.65%)
    11 / 64 (17.19%)
    8 / 54 (14.81%)
    3 / 32 (9.38%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    11
    19
    11
    8
    3
    0
    0
    0
    0
    0
    0
    Pyrexia (fever)
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 59 (5.08%)
    1 / 92 (1.09%)
    3 / 64 (4.69%)
    1 / 54 (1.85%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    1
    3
    1
    1
    0
    0
    0
    0
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastrointestinal somatic symptom disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Generalised anxiety disorder
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Persistent depressive disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Testicular pain
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Fall
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    2 / 54 (3.70%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Head injury
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Joint injury
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Laceration
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Muscle injury
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    Neck injury
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Road traffic accident
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vasoplegia syndrome
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Wrist fracture
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    2 / 54 (3.70%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Borrelia test positive
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cardiac arrest
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Brain injury
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Disturbance in attention
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Headache
    alternative assessment type: Systematic
         subjects affected / exposed
    30 / 59 (50.85%)
    44 / 92 (47.83%)
    36 / 64 (56.25%)
    26 / 54 (48.15%)
    12 / 32 (37.50%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    30
    44
    36
    26
    12
    0
    0
    0
    0
    0
    0
    Orthostatic intolerance
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    1 / 70 (1.43%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Eye disorders
    Myopia
         subjects affected / exposed
    2 / 59 (3.39%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    2
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypermetropia
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    1 / 46 (2.17%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Gastric ulcer
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Impaired gastric emptying
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Diarrhoea
    alternative assessment type: Systematic
         subjects affected / exposed
    6 / 59 (10.17%)
    12 / 92 (13.04%)
    3 / 64 (4.69%)
    3 / 54 (5.56%)
    6 / 32 (18.75%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    6
    12
    3
    3
    6
    0
    0
    0
    0
    0
    0
    Vomiting
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 59 (1.69%)
    3 / 92 (3.26%)
    2 / 64 (3.13%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    3
    2
    1
    0
    0
    0
    0
    0
    0
    0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    1 / 70 (1.43%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Eczema
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Psoriasis
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Arthralgia
    alternative assessment type: Systematic
         subjects affected / exposed
    7 / 59 (11.86%)
    15 / 92 (16.30%)
    9 / 64 (14.06%)
    10 / 54 (18.52%)
    7 / 32 (21.88%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    7
    15
    9
    10
    7
    0
    0
    0
    0
    0
    0
    Myalgia
    alternative assessment type: Systematic
         subjects affected / exposed
    13 / 59 (22.03%)
    27 / 92 (29.35%)
    12 / 64 (18.75%)
    13 / 54 (24.07%)
    5 / 32 (15.63%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    13
    27
    12
    13
    5
    0
    0
    0
    0
    0
    0
    Osteochondrosis
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    1 / 70 (1.43%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    1 / 70 (1.43%)
    0 / 101 (0.00%)
    1 / 277 (0.36%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Electrolyte imbalance
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vitamin K deficiency
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Body tinea
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Cervicitis
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Chlamydial infection
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    1 / 86 (1.16%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    0
    0
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    1 / 64 (1.56%)
    1 / 54 (1.85%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    0
    0
    0
    0
    0
    0
    Genitourinary chlamydia infection
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Impetigo
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Infection
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Influenza
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    2
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Laryngitis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Lower respiratory tract infection viral
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 59 (5.08%)
    2 / 92 (2.17%)
    5 / 64 (7.81%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    2
    5
    1
    0
    0
    0
    0
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Otitis media acute
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    3 / 59 (5.08%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    0
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    2 / 64 (3.13%)
    0 / 54 (0.00%)
    2 / 32 (6.25%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    2
    2
    0
    2
    0
    0
    0
    0
    0
    0
    Tooth infection
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Tracheitis
         subjects affected / exposed
    3 / 59 (5.08%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    3
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 92 (2.17%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    2
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Infectious mononucleosis
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
    0 / 70 (0.00%)
    0 / 101 (0.00%)
    0 / 277 (0.00%)
    0 / 116 (0.00%)
    0 / 86 (0.00%)
    0 / 46 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Mar 2012
    Addition of the benefit-risk assessment in the protocol.
    19 Dec 2013
    Updation of requirement to report serious adverse events back to the primary studies after the active reporting phase, Addition of Section 7.1.2 on the Luminex assay for antigen detection for MCV4, collection of newly diagnosed chronic medical conditions.
    08 Jan 2015
    Addition of a booster dose (booster stage), primary safety objective/endpoints describing the safety profile of bivalent rLP2086 booster vaccination. Updation of safety reporting requirements to reflect receipt of the booster dose.
    18 Apr 2017
    Extension of booster stage follow-up duration from 12 months to 26 months, Addition of an additional blood draw visit (Visit 11) to assess immune response 26 months after the booster dose, Updation of the primary and objectives and corresponding endpoint relating to immunogenicity assessment for the booster stage follow-up at 26 months, primary safety endpoint relating to the booster stage follow-up at 26 months. Addition of Visit 11 to the adverse event, Visit 11 to data analysis for immunogenicity and safety endpoints.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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