Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 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
    		 v1
    This version publication date
    21 Jul 2018
    First version publication date
    21 Jul 2018
    Other versions
    		 v2 , v3 , v4

    Trial information

    		 Close Top of page
    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
    Interim
    Date of interim/final analysis
    29 Mar 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
    Czech Republic: 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

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Total 698 subjects enrolled in study, who completed 1 of primary studies B1971010, B1971012 and B1971015. This study consisted of 2 stages: Stage 1 and Booster stage. Only subjects from primary studies B1971010 and B1971012 who received bivalent rLP2086 in primary study and completed Stage 1 were eligible to participate in 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) and Tetanus, diphtheria, and acellular pertussis (Tdap) vaccine on 0- month, saline on a 0-, 2-, 6- month schedule in primary study B1971015.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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
    		 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 this study.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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
         No longer meets eligibility criteria
    1
    -
    1
    2
    -
    -
         No longer willing to participate
    5
    3
    18
    6
    3
    -
         Other than specified
    5
    -
    9
    -
    -
    -
         Lost to follow-up
    3
    4
    12
    -
    -
    -
         Protocol deviation
    -
    3
    -
    -
    -
    -
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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
    		 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 this study.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.
    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 those subjects from primary study who were eligible to participate in the Booster Stage have started this period.

    Baseline characteristics

    		 Close Top of page
    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) and Tetanus, diphtheria, and acellular pertussis (Tdap) vaccine on 0- month, saline on a 0-, 2-, 6- month schedule in primary study B1971015.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    Reporting group title
    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 this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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
    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

    		 Close Top of page
    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) and Tetanus, diphtheria, and acellular pertussis (Tdap) vaccine on 0- month, saline on a 0-, 2-, 6- month schedule in primary study B1971015.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    Reporting group title
    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 this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage 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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    Reporting group title
    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 this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

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

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Local Reactions Within 7 Days After Booster Vaccination [1]
    End point description
    Local reactions included pain at injection site, redness and swelling collected by using an e-diary. Redness and swelling were graded as: mild (2.5-5.0 centimeter [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
    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 analyzed 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

    		 Close Top of page
    End point title
    		 Percentage of Subjects Reporting Systemic Events and Antipyretic Use Within 7 Days After Booster Vaccination [2]
    End point description
    Systemic reactions included: fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain and joint pain, were recorded by using an e-diary. Fever was graded as: greater than equal to (>=) 38.0 degree celsius (C), 38.0 to less than (<) 38.5 degree C, 38.5 to <39.0 degree C, 39.0 to 40.0 degree C and greater than (>) 40.0°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 activity), 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
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed 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 Visit 7 to Visit 8 (Booster Vaccination Phase)

    		 Close Top of page
    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 Visit 7 to Visit 8 (Booster Vaccination Phase) [3]
    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 to Visit 8
    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 analyzed 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 Visit 8 to Visit 9 (Booster Follow-up Phase)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Visit 8 to Visit 9 (Booster Follow-up Phase) [4]
    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 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 8 to Visit 9
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed 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 Visit 7 to Visit 9

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Serious Adverse Event (SAE) and Medically Attended Adverse Event (MAE) From Visit 7 to Visit 9 [5]
    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 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 to Visit 9 (From booster vaccination through 6 months after booster vaccination)
    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 analyzed 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 to Visit 6 (Stage 1)

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From the 6-Month Safety Telephone call in the Primary Study to Visit 6 (Stage 1) [6]
    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 to Visit 6 (6 months after last primary dose to 48 months after last primary dose in primary study)
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed 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 Visit 8 to Visit 10

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Visit 8 to Visit 10 [7]
    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 to Visit 10 (From 1 month after booster vaccination through 12 months after booster vaccination)
    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 analyzed 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 Visit 7 to Visit 10

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Newly Diagnosed Chronic Medical Condition (NDCMC) From Visit 7 to Visit 10 [8]
    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 to Visit 10 (From booster vaccination through 12 months after booster vaccination)
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed 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 Visit 8 to Visit 11

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Visit 8 to Visit 11 [9]
    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. ‘Number of subjects analyzed’= subjects who were in the safety population for the specified analysis interval.
    End point type
    Primary
    End point timeframe
    From Visit 8 to Visit 11 (From 1 month after booster vaccination through 26 months after booster vaccination)
    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 analyzed 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
    0 [10]
    37
    49
    0 [11]
    0 [12]
    Units: percentage of subjects
        number (confidence interval 95%)
    ( to )
    5.4 (0.7 to 18.2)
    0.0 (0.0 to 7.3)
    ( to )
    ( to )
    Notes
    [10] - None of the subject analyzed for the specified time point.
    [11] - None of the subject analyzed for the specified time point.
    [12] - None of the subject analyzed for the specified time point.
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Visit 7 to Visit 11

    		 Close Top of page
    End point title
    		 Percentage of Subjects With Newly Diagnosed Chronic Medical Condition (NDCMC) From Visit 7 to Visit 11 [13]
    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. ‘Number of subjects analyzed’= subjects who were in the safety population for the specified analysis interval.
    End point type
    Primary
    End point timeframe
    From Visit 7 to Visit 11 (From booster vaccination through 26 months after booster vaccination)
    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 analyzed 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
    0 [14]
    37
    49
    0 [15]
    0 [16]
    Units: percentage of subjects
        number (confidence interval 95%)
    ( to )
    5.4 (0.7 to 18.2)
    0.0 (0.0 to 7.3)
    ( to )
    ( to )
    Notes
    [14] - None of the subject analyzed for the specified time point.
    [15] - None of the subject analyzed for the specified time point.
    [16] - None of the subject analyzed for the specified time point.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Percentage of Subjects With at Least 1 Immediate Adverse Event (AE) After Booster Vaccination [17]
    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 days after booster vaccination
    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 analyzed 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 Visit 7 Through Visit 9

    		 Close Top of page
    End point title
    		 Number of Days Subjects Missed Work or School Due to AE From Visit 7 Through Visit 9 [18]
    End point description
    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 Through Visit 9 (From booster vaccination through 6 months after booster vaccination)
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive data was planned to be analyzed 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: days
    12
    12
    8
    3
    6
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    SAEs: Recorded from Booster vaccination through visit 7 to 11 (Month 26). Subjects recorded local reactions and systemic events in e-diary within 7 days after booster vaccination. NSAEs: Recorded from Booster vaccination through visit 7 to 11 (Month 26).
    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.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    Reporting group title
    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 this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    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, received intramuscular injection of 120 mcg of bivalent rLP2086 vaccine at Visit 7 (approximately Month 48) in booster stage of this study.

    Serious adverse events
    		 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 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%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Meniscus injury
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    1 / 54 (1.85%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pyelonephritis
         subjects affected / exposed
    0 / 59 (0.00%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 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 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%)
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    0
    0
    0
    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%)
         occurrences all number
    0
    0
    0
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    14
    29
    13
    10
    9
    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%)
         occurrences all number
    37
    56
    40
    28
    21
    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%)
         occurrences all number
    12
    19
    13
    15
    2
    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%)
         occurrences all number
    54
    86
    57
    48
    27
    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%)
         occurrences all number
    11
    19
    11
    8
    3
    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%)
         occurrences all number
    3
    1
    3
    1
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    1
    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%)
         occurrences all number
    1
    1
    0
    2
    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%)
         occurrences all number
    0
    1
    1
    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%)
         occurrences all number
    0
    0
    1
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    1
    1
    0
    0
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    0
    0
    0
    2
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    0
    2
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    2
    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%)
         occurrences all number
    0
    0
    0
    1
    1
    Syncope
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    30
    44
    36
    26
    12
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    2
    1
    0
    0
    0
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    6
    12
    3
    3
    6
    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%)
         occurrences all number
    1
    3
    2
    1
    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%)
         occurrences all number
    0
    0
    0
    0
    1
    Eczema
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 92 (1.09%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    0
    1
    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%)
         occurrences all number
    0
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    1
    0
    1
    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%)
         occurrences all number
    7
    15
    9
    10
    7
    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%)
         occurrences all number
    13
    27
    12
    13
    5
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    0
    1
    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%)
         occurrences all number
    0
    0
    0
    1
    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%)
         occurrences all number
    1
    0
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    0
    1
    1
    1
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    0
    1
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    2
    0
    0
    0
    1
    Laryngitis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    1
    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%)
         occurrences all number
    3
    2
    5
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    0
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    3 / 59 (5.08%)
    0 / 92 (0.00%)
    1 / 64 (1.56%)
    0 / 54 (0.00%)
    1 / 32 (3.13%)
         occurrences all number
    3
    0
    1
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 92 (0.00%)
    0 / 64 (0.00%)
    0 / 54 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    2
    2
    0
    2
    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%)
         occurrences all number
    0
    0
    0
    1
    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%)
         occurrences all number
    3
    0
    0
    0
    1
    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%)
         occurrences all number
    1
    2
    0
    0
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    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%)
         occurrences all number
    1
    0
    0
    0
    0

    More information

    		 Close Top of page

    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.
    Immunogenicity data will be posted when it is available.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 02:44:07 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA