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    Clinical Trial Results:
    A Phase I/II, observer-blind, randomised, placebo-controlled study to assess safety, immunogenicity and efficacy of GSK S. aureus candidate vaccine when administered to healthy adults (dose-escalation) and to adults 18 to 64 years of age with a recent S. aureus skin and soft tissue infection (SSTI)

    Summary
    EudraCT number
    		 2021-006215-29
    Trial protocol
    		 PL  
    Global end of trial date
    12 Mar 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Mar 2025
    First version publication date
    26 Mar 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    208833
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    Rue de l’Institut, 89, Rixensart, Belgium, 1330
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    21 Jun 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Mar 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To assess safety and reactogenicity of investigational S. aureus vaccine • To evaluate VE in the prevention of recurrent culture confirmed S. aureus SSTIs compared to placebo
    Protection of trial subjects
    The participants were observed closely for at least 60 minutes following the administration of vaccine/placebo, with appropriate medical treatment readily available in case of anaphylaxis and syncope.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jun 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 41
    Country: Number of subjects enrolled
    India: 63
    Country: Number of subjects enrolled
    New Zealand: 31
    Country: Number of subjects enrolled
    Poland: 14
    Country: Number of subjects enrolled
    South Africa: 21
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    United States: 51
    Worldwide total number of subjects
    226
    EEA total number of subjects
    14
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    226
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 In SLI and PoP, a total of 376 participants were screened, of which 149 were screening failures and 227 were enrolled. One of the enrolled participants was not included in the analysis population due to a protocol deviation.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Observer-blind

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj)
    Arm description
    		 Participants received 1 dose of the half dose formulation of the vaccine on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sa-5Ag half dose nonadjuvanted
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant

    Arm title
    		 Group 2 Dose-escalation Epoch: Full dose Non-Adj
    Arm description
    		 Participants received 1 dose of the full dose formulation of the vaccine on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sa-5Ag full dose nonadjuvanted
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant

    Arm title
    		 Group 3 Dose-escalation Epoch: Half dose Adj
    Arm description
    		 Participants received 1 dose of the half dose formulation of the vaccine with adjuvant on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sa-5Ag half dose adjuvanted
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant

    Arm title
    		 Group 4 Dose-escalation Epoch: Full dose Adj
    Arm description
    		 Participants received 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sa-5Ag full dose adjuvanted
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses per participant

    Arm title
    		 Dose-escalation Epoch: Placebo
    Arm description
    		 Participants received matching placebo on Day 1 for Group 1, Group 2 and Group 3, and on Day 1 and Day 61 for Group 4 of the escalation epoch.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant for Group 1, Group 2 and Group 3, and 2 doses per participant for Group 4

    Arm title
    		 Proof of Principle (PoP): Full dose Adj
    Arm description
    		 Participants were randomized to receive 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sa-5Ag full dose adjuvanted
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses per participant

    Arm title
    		 PoP: Placebo
    Arm description
    		 Participants were randomized to receive 2 doses of placebo on Day 1 and Day 61.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses per participant

    Number of subjects in period 1
    		Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Started
    6
    6
    6
    6
    8
    105
    89
    Completed
    6
    6
    6
    6
    8
    80
    79
    Not completed
    0
    0
    0
    0
    0
    25
    10
         Migrated / Moved from the Study Area
    -
    -
    -
    -
    -
    1
    2
         Consent withdrawn by subject
    -
    -
    -
    -
    -
    20
    5
         Other
    -
    -
    -
    -
    -
    1
    1
         Lost to follow-up
    -
    -
    -
    -
    -
    3
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj)
    Reporting group description
    		 Participants received 1 dose of the half dose formulation of the vaccine on Day 1.

    Reporting group title
    Group 2 Dose-escalation Epoch: Full dose Non-Adj
    Reporting group description
    		 Participants received 1 dose of the full dose formulation of the vaccine on Day 1.

    Reporting group title
    Group 3 Dose-escalation Epoch: Half dose Adj
    Reporting group description
    		 Participants received 1 dose of the half dose formulation of the vaccine with adjuvant on Day 1.

    Reporting group title
    Group 4 Dose-escalation Epoch: Full dose Adj
    Reporting group description
    		 Participants received 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

    Reporting group title
    Dose-escalation Epoch: Placebo
    Reporting group description
    		 Participants received matching placebo on Day 1 for Group 1, Group 2 and Group 3, and on Day 1 and Day 61 for Group 4 of the escalation epoch.

    Reporting group title
    Proof of Principle (PoP): Full dose Adj
    Reporting group description
    		 Participants were randomized to receive 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

    Reporting group title
    PoP: Placebo
    Reporting group description
    		 Participants were randomized to receive 2 doses of placebo on Day 1 and Day 61.

    Reporting group values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj PoP: Placebo Total
    Number of subjects
    		 6 6 6 6 8 105 89 226
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0 0 0 0 0
        Between 18 and 65 years
    		 6 6 6 6 8 105 89 226
        >=65 years
    		 0 0 0 0 0 0 0 0
    Sex: Female, Male
    Units: Participants
        MALE
    		 3 1 1 4 2 61 55 127
        FEMALE
    		 3 5 5 2 6 44 34 99
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 1 0 0 0 0 2 2 5
        Not Hispanic or Latino
    		 5 6 6 6 8 66 58 155
        Not reported
    		 0 0 0 0 0 37 29 66

    End points

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    End points reporting groups
    Reporting group title
    Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj)
    Reporting group description
    		 Participants received 1 dose of the half dose formulation of the vaccine on Day 1.

    Reporting group title
    Group 2 Dose-escalation Epoch: Full dose Non-Adj
    Reporting group description
    		 Participants received 1 dose of the full dose formulation of the vaccine on Day 1.

    Reporting group title
    Group 3 Dose-escalation Epoch: Half dose Adj
    Reporting group description
    		 Participants received 1 dose of the half dose formulation of the vaccine with adjuvant on Day 1.

    Reporting group title
    Group 4 Dose-escalation Epoch: Full dose Adj
    Reporting group description
    		 Participants received 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

    Reporting group title
    Dose-escalation Epoch: Placebo
    Reporting group description
    		 Participants received matching placebo on Day 1 for Group 1, Group 2 and Group 3, and on Day 1 and Day 61 for Group 4 of the escalation epoch.

    Reporting group title
    Proof of Principle (PoP): Full dose Adj
    Reporting group description
    		 Participants were randomized to receive 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

    Reporting group title
    PoP: Placebo
    Reporting group description
    		 Participants were randomized to receive 2 doses of placebo on Day 1 and Day 61.

    Primary: Dose-escalation safety lead-in: Number of participants with any and grade 3 solicited administration site adverse events (AEs) after each vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with any and grade 3 solicited administration site adverse events (AEs) after each vaccination [1] [2]
    End point description
    The solicited administration site AE(s) assessed are pain, redness and swelling. Any = any solicited administration site AE, regardless of intensity; Grade 3 Pain at injection site = Severe, significant pain at rest, that prevents normal everyday activities; Grade 3 redness/swelling = greater than (>)100 millimeter (mm) diameter. The analysis was performed on Solicited Safety Set (SSS) which included all subjects who received at least 1 dose of the study treatment (Exposed Set) who have solicited safety data. Analysis is presented for Dose-escalation safety lead-in participants. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination [day of administration and 6 subsequent days post-each vaccination; Vaccination 1 (V1) on Day 1 and Vaccination 2 (V2) on Day 61]
    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: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    [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: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    6
    6
    6
    8
    Units: Participants
        V1, Pain at injection site, Any (N=6;6;6;6;8)
    2
    3
    5
    5
    1
        V1, Pain at injection site, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Redness at injection site, Any (N=6;6;6;6;8)
    0
    1
    0
    2
    0
        V1, Redness at injection site, >100mm(N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Swelling at injection site, Any (N=6;6;6;6;8)
    0
    0
    0
    1
    0
        V1,Swelling at injection site, >100mm(N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V2, Pain at injection site, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    6
    0
        V2, Pain at injection site, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Redness at injection site, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    3
    0
        V2, Redness at injection site, >100mm(N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Swelling at injection site, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    3
    0
        V2,Swelling at injection site, >100mm(N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
    No statistical analyses for this end point

    Primary: PoP: Number of participants with any and grade 3 solicited administration site AEs after each vaccination

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    End point title
    		 PoP: Number of participants with any and grade 3 solicited administration site AEs after each vaccination [3] [4]
    End point description
    The solicited administration site AEs assessed are pain, redness and swelling. Any = any solicited administration site AE, regardless of intensity; Grade 3 Pain at injection site = Severe, significant pain at rest, that prevents normal everyday activities; Grade 3 redness/swelling = greater than (>)100 millimeter (mm) diameter. The analysis was performed on Solicited Safety Set (SSS). Analysis is presented for PoP participants.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination [day of administration and 6 subsequent days post-each vaccination; Vaccination 1 (V1) on Day 1 and Vaccination 2 (V2) on Day 61]
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [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: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    102
    88
    Units: Participants
        V1, Pain at injection site, Any (N=102;88)
    56
    11
        V1, Pain at injection site, Severe (N=102;88)
    2
    0
        V1, Redness at injection site, Any (N=102;88)
    4
    0
        V1, Redness at injection site, >100mm (N=102;88)
    1
    0
        V1, Swelling at injection site, Any (N=102;88)
    7
    1
        V1, Swelling at injection site, >100mm (N=102;88)
    2
    1
        V2, Pain at injection site, Any (N=66;47)
    42
    2
        V2, Pain at injection site, Severe (N=66;47)
    3
    0
        V2, Redness at injection site, Any (N=66;47)
    10
    0
        V2, Redness at injection site, >100mm (N=66;47)
    4
    0
        V2, Swelling at injection site, Any (N=66;47)
    13
    0
        V2, Swelling at injection site, >100mm (N=66;47)
    3
    0
    No statistical analyses for this end point

    Primary: Dose-escalation safety lead-in: Number of participants with any and Grade 3 solicited systemic AEs after each vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with any and Grade 3 solicited systemic AEs after each vaccination [5] [6]
    End point description
    The solicited systemic AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever. Any = any solicited systemic AE regardless of intensity; Grade 3 headache/fatigue/nausea/abdominal pain/myalgia/shivering = Severe: Prevents daily activity. Grade 3 vomiting = Severe: 6 or more times in 24 hours or requires intravenous hydration. Grade 3 diarrhea = Severe: 6 or more loose stools in 24 hours or requires intravenous hydration. Grade 3 fever = body temperature greater than (>) 40.0°C/104°F. The analysis was performed on Solicited Safety Set (SSS). Analysis is presented for Dose-escalation safety lead-in participants. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination [day of administration and 6 subsequent days post-each vaccination; Vaccination 1 (V1) on Day 1 and Vaccination 2 (V2) on Day 61]
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [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: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    6
    6
    6
    8
    Units: Participants
        V1, Abdominal Pain, Any (N=6;6;6;6;8)
    0
    1
    0
    0
    1
        V1, Abdominal Pain, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Diarrhea, Any (N=6;6;6;6;8)
    0
    1
    1
    1
    0
        V1, Diarrhea, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Fatigue, Any (N=6;6;6;6;8)
    1
    2
    3
    3
    2
        V1, Fatigue, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Fever, Any (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Fever (°C), > 40.0 (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Headache, Any (N=6;6;6;6;8)
    0
    3
    2
    1
    4
        V1, Headache, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Myalgia, Any (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Myalgia, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Nausea, Any (N=6;6;6;6;8)
    0
    1
    2
    0
    1
        V1, Nausea, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    1
        V1, Shivering, Any (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Shivering, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Vomiting, Any (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1, Vomiting, Severe (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V2, Abdominal Pain, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Abdominal Pain, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Diarrhea, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Diarrhea, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Fatigue, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    5
    0
        V2, Fatigue, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    1
    0
        V2, Fever, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    3
    0
        V2, Fever (°C), > 40.0 (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Headache, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    3
    0
        V2, Headache, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    1
    0
        V2, Myalgia, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Myalgia, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Nausea, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    2
    0
        V2, Nausea, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Shivering, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Shivering, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Vomiting, Any (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2, Vomiting, Severe (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
    No statistical analyses for this end point

    Primary: PoP: Number of participants with any and Grade 3 solicited systemic AEs after each vaccination

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    End point title
    		 PoP: Number of participants with any and Grade 3 solicited systemic AEs after each vaccination [7] [8]
    End point description
    The solicited systemic AE(s) assessed are headache, fatigue, nausea, vomiting, diarrhea, abdominal pain, myalgia, shivering and fever were assessed. Any = any solicited systemic AE regardless of intensity; Grade 3 headache/fatigue/nausea/abdominal pain/myalgia/shivering = Severe: Prevents daily activity. Grade 3 vomiting = Severe: 6 or more times in 24 hours or requires intravenous hydration. Grade 3 diarrhea = Severe: 6 or more loose stools in 24 hours or requires intravenous hydration. Grade 3 fever = body temperature greater than (>) 40.0°C/104°F. The analysis was performed on Solicited Safety Set (SSS). Analysis is presented for PoP participants.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination [day of administration and 6 subsequent days post-each vaccination; Vaccination 1 (V1) on Day 1 and Vaccination 2 (V2) on Day 61]
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [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: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    102
    88
    Units: Participants
        V1, Abdominal Pain, Any (N=102;88)
    6
    6
        V1, Abdominal Pain, Severe (N=102;88)
    0
    0
        V1, Diarrhea, Any (N=102;88)
    11
    4
        V1, Diarrhea, Severe (N=102;88)
    0
    0
        V1, Fatigue, Any (N=102;88)
    34
    21
        V1, Fatigue, Severe (N=102;88)
    2
    2
        V1, Fever, Any (N=102;88)
    4
    1
        V1, Fever (°C), > 40.0 (N=102;88)
    0
    0
        V1, Headache, Any (N=102;88)
    28
    26
        V1, Headache, Severe (N=102;88)
    1
    2
        V1, Myalgia, Any (N=102;88)
    16
    10
        V1, Myalgia, Severe (N=102;88)
    1
    0
        V1, Nausea, Any (N=102;88)
    8
    8
        V1, Nausea, Severe (N=102;88)
    0
    0
        V1, Shivering, Any (N=102;88)
    8
    5
        V1, Shivering, Severe (N=102;88)
    0
    0
        V1, Vomiting, Any (N=102;88)
    2
    1
        V1, Vomiting, Severe (N=102;88)
    0
    0
        V2, Abdominal Pain, Any (N=66;47)
    4
    0
        V2, Abdominal Pain, Severe (N=66;47)
    0
    0
        V2, Diarrhea, Any (N=66;47)
    4
    2
        V2, Diarrhea, Severe (N=66;47)
    0
    0
        V2, Fatigue, Any (N=66;47)
    33
    7
        V2, Fatigue, Severe (N=66;47)
    3
    1
        V2, Fever, Any (N=66;47)
    4
    1
        V2, Fever (°C), > 40.0 (N=66;47)
    0
    0
        V2, Headache, Any (N=66;47)
    24
    7
        V2, Headache, Severe (N=66;47)
    3
    0
        V2, Myalgia, Any (N=66;47)
    15
    2
        V2, Myalgia, Severe (N=66;47)
    3
    0
        V2, Nausea, Any (N=66;47)
    11
    4
        V2, Nausea, Severe (N=66;47)
    1
    0
        V2, Shivering, Any (N=66;47)
    11
    1
        V2, Shivering, Severe (N=66;47)
    2
    0
        V2, Vomiting, Any (N=66;47)
    3
    0
        V2, Vomiting, Severe (N=66;47)
    0
    0
    No statistical analyses for this end point

    Primary: Dose-escalation safety lead-in: Number of participants with unsolicited AEs (any, grade 3, related, related grade 3) after each vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with unsolicited AEs (any, grade 3, related, related grade 3) after each vaccination [9] [10]
    End point description
    An unsolicited adverse event is defined as an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. Any unsolicited AE, Grade 3 (G3) unsolicited AE, unsolicited AE causally related to the vaccination and G3 unsolicited AE causally related to the vaccination were assessed. A grade 3 AE is an AE that prevents normal, everyday activities. The analysis was performed on the Unsolicited Safety Set (USS) which included all subjects who received at least 1 dose of the study treatment (Exposed Set) that report unsolicited AEs/report not having unsolicited AEs. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    During 30 days after each vaccination [day of administration and 29 subsequent days post-each vaccination; Vaccination 1 (V1) on Day 1 and Vaccination 2 (V2) on Day 61]
    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: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    [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: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    6
    6
    6
    8
    Units: Participants
        V1,At least 1 unsolicited AE (N=6;6;6;6;8)
    1
    3
    1
    0
    0
        V1,At least 1 related unsolicited AE (N=6;6;6;6;8)
    1
    2
    0
    0
    0
        V1,At least 1 G3 unsolicited AE (N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V1,At least 1 G3 related unsol. AE(N=6;6;6;6;8)
    0
    0
    0
    0
    0
        V2,At least 1 unsolicited AE (N=0;0;0;6;2)
    99999
    99999
    99999
    2
    0
        V2,At least 1 related unsolicited AE (N=0;0;0;6;2)
    99999
    99999
    99999
    2
    0
        V2,At least 1 G3 unsolicited AE (N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
        V2,At least 1 G3 related unsol. AE(N=0;0;0;6;2)
    99999
    99999
    99999
    0
    0
    No statistical analyses for this end point

    Primary: PoP: Number of participants with unsolicited AEs (any, grade 3, related, related grade 3) after each vaccination

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    End point title
    		 PoP: Number of participants with unsolicited AEs (any, grade 3, related, related grade 3) after each vaccination [11] [12]
    End point description
    An unsolicited adverse event is defined as an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. Any unsolicited AE, Grade 3 (G3) unsolicited AE, unsolicited AE causally related to the vaccination and G3 unsolicited AE causally related to the vaccination were assessed. A grade 3 AE is an AE that prevents normal, everyday activities. The analysis was performed on USS.
    End point type
    Primary
    End point timeframe
    During 30 days after each vaccination [day of administration and 29 subsequent days post-each vaccination; Vaccination 1 (V1) on Day 1 and Vaccination 2 (V2) on Day 61]
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [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: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    103
    89
    Units: Participants
        V1,At least 1 unsolicited AE (N=103;89)
    32
    26
        V1,At least 1 related unsolicited AE (N=103;89)
    16
    4
        V1,At least 1 G3 unsolicited AE (N=103;89)
    0
    1
        V1,At least 1 G3 related unsolicited AE (N=103;89)
    0
    0
        V2,At least 1 unsolicited AE (N=67;48)
    23
    7
        V2,At least 1 related unsolicited AE (N=67;48)
    12
    4
        V2,At least 1 G3 unsolicited AE (N=67;48)
    1
    1
        V2,At least 1 G3 related unsolicited AE (N=67;48)
    1
    1
    No statistical analyses for this end point

    Primary: Dose-escalation safety lead-in: Number of participants with serious AEs (SAEs) up to 1 year post first vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with serious AEs (SAEs) up to 1 year post first vaccination [13] [14]
    End point description
    A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. The analysis was performed on the Exposed Set (ES) that included all subjects who received at least 1 dose of the study treatment. The allocation in a group is done in function of the administered treatment.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 366
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    6
    6
    6
    8
    Units: Participants
        At least one SAE
    0
    0
    0
    0
    0
        At least one serious related AE
    0
    0
    0
    0
    0
        Any Grade 3 SAE
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Dose-escalation safety lead-in: Number of participants with SAEs up to 1 year post second vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with SAEs up to 1 year post second vaccination [15] [16]
    End point description
    A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. The analysis was performed on ES. Only participants that received a second vaccination on Day 61 were included in this analysis.
    End point type
    Primary
    End point timeframe
    From Day 61 to Day 426 (post vaccination at Day 61)
    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: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    2
    Units: Participants
        At least one SAE
    0
    0
        At least one serious related AE
    0
    0
        Any Grade 3 SAE
    0
    0
    No statistical analyses for this end point

    Primary: PoP: Number of participants with SAEs

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    End point title
    		 PoP: Number of participants with SAEs [17] [18]
    End point description
    A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. The analysis was performed on ES. The allocation in a group is done in function of the administered treatment.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 426
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    103
    89
    Units: Participants
        At least one SAE
    5
    5
        At least one serious related AE
    0
    0
        Any Grade 3 SAE
    3
    2
    No statistical analyses for this end point

    Primary: Dose-escalation safety lead-in: Number of participants with potential immune-mediated diseases (pIMDs) up to 1 year post first vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with potential immune-mediated diseases (pIMDs) up to 1 year post first vaccination [19] [20]
    End point description
    pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. The analysis was performed on ES.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 366
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    6
    6
    6
    8
    Units: Participants
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Dose-escalation safety lead-in: Number of participants with pIMDs up to 1 year post second vaccination

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    End point title
    		 Dose-escalation safety lead-in: Number of participants with pIMDs up to 1 year post second vaccination [21] [22]
    End point description
    pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. The analysis was performed on ES. Only participants that received a second vaccination on Day 61 were included in this analysis.
    End point type
    Primary
    End point timeframe
    From Day 61 to Day 426 (post vaccination at Day 61)
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint reports data only for the "dose-escalation epoch". Hence, the arms that correspond to only dose-escalation were included.
    End point values
    		 Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo
    Number of subjects analysed
    6
    2
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Primary: PoP: Number of participants with potential immune-mediated diseases (pIMDs)

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    End point title
    		 PoP: Number of participants with potential immune-mediated diseases (pIMDs) [23] [24]
    End point description
    pIMDs are defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. The analysis was performed on ES.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 426
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    103
    89
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Primary: Number of participants with maximum toxicity grade increase from baseline for haematological and biochemical laboratory parameters [On Day 8 compared to Baseline (Day 1)]

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    End point title
    		 Number of participants with maximum toxicity grade increase from baseline for haematological and biochemical laboratory parameters [On Day 8 compared to Baseline (Day 1)] [25]
    End point description
    The parameters were assessed using the FDA toxicity grading scale. Biochemical parameters: Creatinine, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT); Haematological parameters: Haemoglobin (Hb), white blood cells (WBC) decrease, WBC increase, Neutrophils (NEUT) decrease, Platelets (Plt) decrease, Lymphocytes (LYM) decrease, Eosinophils (EOS) increase. Hematological and biochemical laboratory results are defined as follows: <parameter>,<grade at baseline>,<grade at visit> (e.g. ALT, Grade 0, Grade 0). The analysis was performed on the Laboratory Safety Set that was a subset of the Unsolicited Safety Set. Only participants that had available data as per pre-assigned timepoints were included in this analysis. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    On Day 8 compared to Baseline (Day 1)
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    6
    6
    5
    6
    8
    29
    11
    Units: Participants
        ALT, Grade 0, Grade 0 (N=6;6;4;5;8;26;11)
    6
    6
    4
    5
    8
    26
    11
        ALT, Grade 1, Grade 0 (N=0;0;1;1;0;3;0)
    99999
    99999
    1
    1
    99999
    1
    99999
        ALT, Grade 1, Grade 1 (N=0;0;0;0;0;3;0)
    99999
    99999
    99999
    99999
    99999
    2
    99999
        AST, Grade 0, Grade 0 (N=6;6;5;5;8;29;11)
    6
    6
    5
    5
    8
    28
    11
        AST, Grade 0, Grade 1 (N=0;0;0;0;0;29;11)
    99999
    99999
    99999
    99999
    99999
    1
    0
        AST, Grade 1, Grade 0 (N=0;0;0;1;0;0;0)
    99999
    99999
    99999
    1
    99999
    99999
    99999
        Creatinine, Unknown, Grade 0 (N=0;0;0;0;0;0;1)
    99999
    99999
    99999
    99999
    99999
    99999
    1
        Creatinine, Grade 0, Grade 0 (N=6;6;5;6;8;29;10)
    6
    6
    5
    6
    8
    29
    10
        EOS Increase, Grade 0, Grade 0 (N=6;6;5;6;8;27;10)
    6
    6
    5
    6
    8
    27
    10
        EOS Increase, Grade 1, Grade 0 (N=0;0;0;0;0;2;1)
    99999
    99999
    99999
    99999
    99999
    0
    1
        EOS Increase, Grade 1, Grade 1 (N=0;0;0;0;0;2;1)
    99999
    99999
    99999
    99999
    99999
    2
    0
        Hb Decrease, Grade 0, Grade 0 (N=6;5;5;6;8;23;11)
    6
    5
    4
    6
    8
    20
    10
        Hb Decrease, Grade 0, Grade 1 (N=6;5;5;6;8;23;11)
    0
    0
    1
    0
    0
    3
    1
        Hb Decrease, Grade 1, Grade 0 (N=0;0;0;0;0;6;0)
    99999
    99999
    99999
    99999
    99999
    2
    99999
        Hb Decrease, Grade 1, Grade 1 (N=0;1;0;0;0;6;0)
    99999
    1
    99999
    99999
    99999
    4
    99999
        LYM Decrease, Grade 0, Grade 0 (N=6;6;4;6;8;29;11)
    6
    6
    4
    6
    8
    29
    11
        LYM Decrease, Grade 1, Grade 1 (N=0;0;1;0;0;0;0)
    99999
    99999
    1
    99999
    99999
    99999
    99999
        NEUT Decrease,Grade 0, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    7
    29
    11
        NEUT Decrease,Grade 0, Grade 1 (N=6;6;5;6;8;0;0)
    0
    0
    0
    0
    1
    0
    0
        Plt Decrease, Grade 0, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    29
    11
        WBC Decrease, Grade 0, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    29
    11
        WBC Increase, Grade 0, Grade 0 (N=6;6;4;6;7;28;11)
    6
    5
    4
    6
    7
    26
    11
        WBC Increase, Grade 0, Grade 1 (N=6;6;4;6;7;28;11)
    0
    1
    0
    0
    0
    2
    0
        WBC Increase, Grade 1, Grade 0 (N=0;0;1;0;1;1;0)
    99999
    99999
    1
    99999
    1
    1
    99999
    No statistical analyses for this end point

    Primary: Number of participants with maximum toxicity grade increase from baseline for haematological and biochemical laboratory parameters [On Day 68 compared to Baseline (Day 61)]

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    End point title
    		 Number of participants with maximum toxicity grade increase from baseline for haematological and biochemical laboratory parameters [On Day 68 compared to Baseline (Day 61)] [26] [27]
    End point description
    The parameters were assessed using the FDA toxicity grading scale. Biochemical parameters: Creatinine, AST, ALT; Haematological parameters: Hb, WBC decrease, WBC increase, NEUT decrease, Plt decrease, LYM decrease, EOS increase. Hematological and biochemical laboratory results are defined as follows: <parameter>,<grade at baseline>,<grade at visit> (e.g. ALT, Grade 0, Grade 0). The analysis was performed on the Laboratory Safety Set. Only participants that had available data as per pre-assigned timepoints were included in this analysis. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    On Day 68 compared to Baseline (Day 61)
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [27] - 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: This endpoint reports data for both "dose-escalation epoch" and "Proof of Principle (PoP)". Hence, the arms that correspond to dose-escalation and PoP were included.
    End point values
    		 Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    6
    2
    27
    11
    Units: Participants
        ALT, Unknown, Grade 0 (N=0;0;1;0)
    99999
    99999
    1
    99999
        ALT, Grade 0, Grade 0 (N=6;2;26;11)
    6
    2
    26
    11
        ALT, Grade 1, Grade 1 (N=0;0;1;0)
    99999
    99999
    1
    99999
        AST, Unknown, Grade 0 (N=0;0;1;0)
    99999
    99999
    1
    99999
        AST, Grade 0, Grade 0 (N=6;2;27;10)
    6
    2
    26
    10
        AST, Grade 0, Grade 1 (N=0;0;27;10)
    99999
    99999
    1
    0
        AST, Grade 1, Grade 0 (N=0;0;0;1)
    99999
    99999
    99999
    1
        Creatinine, Unknown, Grade 0 (N=0;0;1;0)
    99999
    99999
    1
    99999
        Creatinine, Grade 0, Grade 0 (N=6;2;27;11)
    6
    2
    27
    11
        EOS Increase, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    99999
        EOS Increase, Grade 0, Grade 0 (N=5;2;26;10)
    5
    2
    25
    10
        EOS Increase, Grade 0, Grade 1 (N=0;0;26;10)
    99999
    99999
    1
    0
        EOS Increase, Grade 1, Grade 1 (N=0;0;1;1)
    99999
    99999
    1
    1
        Hb Decrease, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    99999
        Hb Decrease, Grade 0, Grade 0 (N=5;2;23;9)
    5
    2
    21
    9
        Hb Decrease, Grade 0, Grade 1 (N=0;0;23;9)
    99999
    99999
    2
    0
        Hb Decrease, Grade 1, Grade 0 (N=0;0;4;2)
    99999
    99999
    2
    0
        Hb Decrease, Grade 1, Grade 1 (N=0;0;4;2)
    99999
    99999
    1
    2
        Hb Decrease, Grade 1, Grade 2 (N=0;0;4;2)
    99999
    99999
    1
    0
        LYM Decrease, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    0
        LYM Decrease, Grade 0, Grade 0 (N=5;2;27;11)
    5
    2
    26
    11
        LYM Decrease, Grade 0, Grade 1 (N=0;0;27;11)
    99999
    99999
    1
    0
        NEUT Decrease, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    99999
        NEUT Decrease, Grade 0, Grade 0 (N=5;2;25;11)
    5
    2
    25
    11
        NEUT Decrease, Grade 1, Grade 0 (N=0;0;2;0)
    99999
    99999
    1
    99999
        NEUT Decrease, Grade 1, Grade 1 (N=0;0;2;0)
    99999
    99999
    1
    99999
        Plt Decrease, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    99999
        Plt Decrease, Grade 0, Grade 0 (N=5;2;27;11)
    5
    2
    27
    11
        WBC Decrease, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    99999
        WBC Decrease, Grade 0, Grade 0 (N=5;2;26;11)
    5
    2
    26
    11
        WBC Decrease, Grade 1, Grade 0 (N=0;0;1;0)
    99999
    99999
    1
    99999
        WBC Increase, Unknown, Grade 0 (N=1;0;1;0)
    1
    99999
    1
    99999
        WBC Increase, Grade 0, Grade 0 (N=5;2;26;11)
    5
    2
    25
    10
        WBC Increase, Grade 0, Grade 1 (N=0;0;26;11)
    99999
    99999
    1
    1
        WBC Increase, Grade 1, Grade 0 (N=0;0;1;0)
    99999
    99999
    1
    99999
    No statistical analyses for this end point

    Primary: Number of participants with haematological and biochemical laboratory change from baseline values [On Day 8]

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    End point title
    		 Number of participants with haematological and biochemical laboratory change from baseline values [On Day 8] [28]
    End point description
    Biochemical parameters: Creatinine, AST, ALT; Haematological parameters: Hb, WBC decrease, WBC increase, NEUT decrease, Plt decrease, LYM decrease, EOS increase. Hematological and biochemical laboratory results are defined as follows: <parameter>,<any grade at baseline>,<grade at visit> (e.g. ALT, Any, Grade 0). The analysis was performed on the Laboratory Safety Set. Only participants that had available data as per pre-assigned timepoints were included in this analysis. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    On Day 8
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    6
    6
    5
    6
    8
    29
    11
    Units: Participants
        ALT, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    27
    11
        ALT, Any, Grade 1 (N=0;0;0;0;0;29;11)
    99999
    99999
    99999
    99999
    99999
    2
    0
        AST, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    28
    11
        AST, Any, Grade 1 (N=0;0;0;0;0;29;11)
    99999
    99999
    99999
    99999
    99999
    1
    0
        Creatinine, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    29
    11
        EOS Increase, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    27
    11
        EOS Increase, Any, Grade 1 (N=0;0;0;0;0;29;11)
    99999
    99999
    99999
    99999
    99999
    2
    0
        Hb Decrease, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    5
    4
    6
    8
    22
    10
        Hb Decrease, Any, Grade 1 (N=6;6;5;6;8;29;11)
    0
    1
    1
    0
    0
    7
    1
        LYM Decrease, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    4
    6
    8
    29
    11
        LYM Decrease, Any, Grade 1 (N=6;6;5;6;8;0;0)
    0
    0
    1
    0
    0
    99999
    99999
        NEUT Decrease, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    7
    29
    11
        NEUT Decrease, Any, Grade 1 (N=6;6;5;6;8;0;0)
    0
    0
    0
    0
    1
    99999
    99999
        Plt Decrease, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    29
    11
        WBC Decrease, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    6
    5
    6
    8
    29
    11
        WBC Increase, Any, Grade 0 (N=6;6;5;6;8;29;11)
    6
    5
    5
    6
    8
    27
    11
        WBC Increase, Any, Grade 1 (N=6;6;5;6;8;29;11)
    0
    1
    0
    0
    0
    2
    0
    No statistical analyses for this end point

    Primary: Number of participants with haematological and biochemical laboratory change from baseline values [On Day 68]

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    End point title
    		 Number of participants with haematological and biochemical laboratory change from baseline values [On Day 68] [29] [30]
    End point description
    Biochemical parameters: Creatinine, AST, ALT; Haematological parameters: Hb, WBC decrease, WBC increase, NEUT decrease, Plt decrease, LYM decrease, EOS increase. Hematological and biochemical laboratory results are defined as follows: <parameter>,<any grade at baseline>,<grade at visit> (e.g. ALT, Any, Grade 0). The analysis was performed on the Laboratory Safety Set. Only participants that had available data as per pre-assigned timepoints were included in this analysis. '99999' was entered as a placeholder value in those instances where there were 0 participants analyzed.
    End point type
    Primary
    End point timeframe
    On Day 68
    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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [30] - 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: This endpoint reports data for both "dose-escalation epoch" and "Proof of Principle (PoP)". Hence, the arms that correspond to dose-escalation and PoP were included.
    End point values
    		 Group 4 Dose-escalation Epoch: Full dose Adj Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    6
    2
    28
    11
    Units: Participants
        ALT, Any, Grade 0 (N=6;2;28;11)
    6
    2
    27
    11
        ALT, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    1
    0
        AST, Any, Grade 0 (N=6;2;28;11)
    6
    2
    27
    11
        AST, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    1
    0
        Creatinine, Any, Grade 0 (N=6;2;28;11)
    6
    2
    28
    11
        EOS Increase, Any, Grade 0 (N=6;2;28;11)
    6
    2
    26
    10
        EOS Increase, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    2
    1
        Hb Decrease, Any, Grade 0 (N=6;2;28;11)
    6
    2
    24
    9
        Hb Decrease, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    3
    2
        Hb Decrease, Any, Grade 2 (N=0;0;28;11)
    99999
    99999
    1
    0
        LYM Decrease, Any, Grade 0 (N=6;2;28;11)
    6
    2
    27
    11
        LYM Decrease, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    1
    0
        NEUT Decrease, Any, Grade 0 (N=6;2;28;11)
    6
    2
    27
    11
        NEUT Decrease, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    1
    0
        Plt Decrease, Any, Grade 0 (N=6;2;28;11)
    6
    2
    28
    11
        WBC Decrease, Any, Grade 0 (N=6;2;28;11)
    6
    2
    28
    11
        WBC Increase, Any, Grade 0 (N=6;2;28;11)
    6
    2
    27
    10
        WBC Increase, Any, Grade 1 (N=0;0;28;11)
    99999
    99999
    1
    1
    No statistical analyses for this end point

    Secondary: Number of participants with at least one culture confirmed case of recurrent Staphylococcus aureus (S. aureus) Skin and Soft Tissue Infection (SSTI) - Interim Analysis

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    End point title
    		 Number of participants with at least one culture confirmed case of recurrent Staphylococcus aureus (S. aureus) Skin and Soft Tissue Infection (SSTI) - Interim Analysis [31]
    End point description
    An interim analysis was performed after 13 cases of recurrent SA-SSTI were reported following 14 days from the study intervention dose 2. The analysis was performed on Interim analysis Proof of Principle (Pop) - modified Full Analysis Set (mFAS) which included all subjects who received full study treatment course to which they are randomised and have post-vaccination efficacy data.
    End point type
    Secondary
    End point timeframe
    From Day 75 to Day 426
    Notes
    [31] - 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: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    38
    21
    Units: Participants
    10
    3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    One-sided Group Sequential Design with non-binding beta, yielding two CIs based on cumulative alpha (92.5%) and beta (80.5%) spending.
    Comparison groups
    Proof of Principle (PoP): Full dose Adj v PoP: Placebo
    Number of subjects included in analysis
    59
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 > 0.8042
    Method
    		 Logrank
    Parameter type
    		 Vaccine Efficacy (VE)
    Point estimate
    -74.76
    Confidence interval
         level
    		 92.5%
         sides
    2-sided
         lower limit
    		 -680.61
         upper limit
    		 36.62
    Notes
    [32] - Vaccine Efficacy (VE) is defined as 1 minus the hazard ratio times 100.

    Secondary: Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI - Final Analysis [From Day 75 to Day 426]

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    End point title
    		 Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI - Final Analysis [From Day 75 to Day 426] [33]
    End point description
    After encountering futility at the interim analysis, an EOS analysis was conducted when at least one culture-confirmed case of recurrent SA-SSTI was identified 14 days after the second dose of the vaccine. For the final analysis, all the data collected by End of Study (EoS; Last Participant Last Visit) were analyzed for descriptive purposes. The analysis was performed on EoS analysis PoP mFAS.
    End point type
    Secondary
    End point timeframe
    From Day 75 to Day 426
    Notes
    [33] - 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: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    66
    48
    Units: Participants
    14
    8
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Proof of Principle (PoP): Full dose Adj v PoP: Placebo
    Number of subjects included in analysis
    114
    Analysis specification
    Pre-specified
    Analysis type
    		 other [34]
    Method
    Parameter type
    		 Vaccine Efficacy (VE)
    Point estimate
    -38.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -245.77
         upper limit
    		 40.86
    Notes
    [34] - Vaccine Efficacy (VE) is defined as 1 minus the hazard ratio times 100.

    Secondary: Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI - Final Analysis [From Day 15 to Day 426]

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    End point title
    		 Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI - Final Analysis [From Day 15 to Day 426] [35]
    End point description
    An EOS analysis was conducted when at least one culture-confirmed case of recurrent SA-SSTI was identified 14 days after the first dose of the vaccine. For the final analysis, all the data collected by End of Study (EoS; Last Participant Last Visit) were analyzed for descriptive purposes. The analysis was performed on the EOS Pop: Full Analysis Set (FAS) which included all subjects who received at least 1 dose of the study treatment and have post-vaccination efficacy data.
    End point type
    Secondary
    End point timeframe
    From Day 15 to Day 426
    Notes
    [35] - 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: This endpoint reports data only for the "Proof of Principle (PoP)". Hence, the arms that correspond to only PoP were included.
    End point values
    		 Proof of Principle (PoP): Full dose Adj PoP: Placebo
    Number of subjects analysed
    103
    89
    Units: Participants
    18
    10
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Proof of Principle (PoP): Full dose Adj v PoP: Placebo
    Number of subjects included in analysis
    192
    Analysis specification
    Pre-specified
    Analysis type
    		 other [36]
    Method
    Parameter type
    		 Vaccine Efficacy (VE)
    Point estimate
    -75.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -295.41
         upper limit
    		 17.46
    Notes
    [36] - Vaccine Efficacy (VE) is defined as 1 minus the hazard ratio times 100.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited AEs: from Day (D) 1 to D7 and D61 to D67 [for Group 4 (G4) and PoP epoch]. Unsolicited AEs: from D1 to D30 and D61 to D90 (for G4 and PoP epoch). SAEs and pIMDs: from D1 to D366 (dose escalation), D61 to D426 (for G4), D1 to D426 for PoP epoch.
    Adverse event reporting additional description
    Adverse events are reported on the Exposed Set, overall and per any dose administration.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 v22.1
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj)
    Reporting group description
    		 Participants received 1 dose of the half dose formulation of the vaccine on Day 1.

    Reporting group title
    Group 2 Dose-escalation Epoch: Full dose Non-Adj
    Reporting group description
    		 Participants received 1 dose of the full dose formulation of the vaccine on Day 1.

    Reporting group title
    Group 3 Dose-escalation Epoch: Half dose Adj
    Reporting group description
    		 Participants received 1 dose of the half dose formulation of the vaccine with adjuvant on Day 1.

    Reporting group title
    PoP: Placebo
    Reporting group description
    		 Participants were randomized to receive 2 doses of placebo on Day 1 and Day 61.

    Reporting group title
    Dose-escalation Epoch: Placebo
    Reporting group description
    		 Participants received matching placebo on Day 1 for Group 1, Group 2 and Group 3, and on Day 1 and Day 61 for Group 4 of the escalation epoch.

    Reporting group title
    Proof of Principle (PoP): Full dose Adj
    Reporting group description
    		 Participants were randomized to receive 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

    Reporting group title
    Group 4 Dose-escalation Epoch: Full dose Adj
    Reporting group description
    		 Participants received 2 doses of the full dose formulation of the vaccine with adjuvant on Day 1 and Day 61.

    Serious adverse events
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj PoP: Placebo Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj Group 4 Dose-escalation Epoch: Full dose Adj
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    5 / 89 (5.62%)
    0 / 8 (0.00%)
    5 / 103 (4.85%)
    0 / 6 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Large intestine benign neoplasm
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Thermal burn
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    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
    Cellulitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Furuncle
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Group 1 Dose-escalation Epoch: Half dose Non-Adjuvant(Non-Adj) Group 2 Dose-escalation Epoch: Full dose Non-Adj Group 3 Dose-escalation Epoch: Half dose Adj PoP: Placebo Dose-escalation Epoch: Placebo Proof of Principle (PoP): Full dose Adj Group 4 Dose-escalation Epoch: Full dose Adj
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 6 (50.00%)
    6 / 6 (100.00%)
    5 / 6 (83.33%)
    60 / 89 (67.42%)
    5 / 8 (62.50%)
    82 / 103 (79.61%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acrochordon
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Hot flush
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    6 / 89 (6.74%)
    0 / 8 (0.00%)
    20 / 103 (19.42%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    6
    0
    22
    0
    Fatigue
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    24 / 89 (26.97%)
    2 / 8 (25.00%)
    46 / 103 (44.66%)
    5 / 6 (83.33%)
         occurrences all number
    1
    2
    3
    29
    2
    70
    8
    Feeling hot
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Injection site macule
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site induration
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Injection site erythema
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    12 / 103 (11.65%)
    3 / 6 (50.00%)
         occurrences all number
    1
    1
    0
    0
    0
    16
    6
    Injection site mass
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site rash
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injection site pain
         subjects affected / exposed
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    5 / 6 (83.33%)
    13 / 89 (14.61%)
    1 / 8 (12.50%)
    65 / 103 (63.11%)
    6 / 6 (100.00%)
         occurrences all number
    2
    4
    5
    14
    1
    114
    13
    Injection site reaction
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vaccination site erythema
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    3 / 89 (3.37%)
    0 / 8 (0.00%)
    12 / 103 (11.65%)
    3 / 6 (50.00%)
         occurrences all number
    0
    0
    0
    3
    0
    12
    3
    Pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    4 / 103 (3.88%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    0
    Injection site swelling
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    16 / 103 (15.53%)
    3 / 6 (50.00%)
         occurrences all number
    0
    0
    0
    1
    0
    23
    5
    Reproductive system and breast disorders
    Menstruation irregular
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Rhinorrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    2 / 103 (1.94%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Dyspnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Cough
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    3 / 89 (3.37%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    1
    0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Psychiatric disorders
    Anxiety disorder
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Arthropod sting
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Fall
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 89 (2.25%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Muscle rupture
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Skin graft failure
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Skin laceration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Lethargy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    2 / 103 (1.94%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Headache
         subjects affected / exposed
    0 / 6 (0.00%)
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    28 / 89 (31.46%)
    4 / 8 (50.00%)
    40 / 103 (38.83%)
    3 / 6 (50.00%)
         occurrences all number
    0
    3
    2
    37
    4
    58
    4
    Dizziness
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Sciatica
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    4 / 103 (3.88%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    4
    0
    Neutropenia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Eye disorders
    Eye inflammation
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    4 / 89 (4.49%)
    0 / 8 (0.00%)
    14 / 103 (13.59%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    1
    8
    0
    17
    1
    Dyspepsia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Angular cheilitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Abdominal pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    6 / 89 (6.74%)
    1 / 8 (12.50%)
    10 / 103 (9.71%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    6
    1
    12
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Vomiting
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    5 / 103 (4.85%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    7
    0
    Toothache
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    10 / 89 (11.24%)
    1 / 8 (12.50%)
    18 / 103 (17.48%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    2
    12
    1
    23
    2
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pain of skin
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Photodermatosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 89 (2.25%)
    0 / 8 (0.00%)
    2 / 103 (1.94%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Eczema
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Acne
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Blister
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Dermatitis atopic
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Fibromyalgia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Exostosis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Arthralgia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    2 / 103 (1.94%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    0
    Back pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    1
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    2 / 103 (1.94%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    Myalgia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    10 / 89 (11.24%)
    0 / 8 (0.00%)
    27 / 103 (26.21%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    13
    0
    32
    2
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Infections and infestations
    Candida infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    COVID-19
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    3 / 89 (3.37%)
    0 / 8 (0.00%)
    4 / 103 (3.88%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    4
    0
    Ear infection staphylococcal
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Eye infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Laryngitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    Impetigo
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Hordeolum
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    Herpes simplex
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Furuncle
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Otitis externa
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Skin infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Staphylococcal skin infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    Viral infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 89 (1.12%)
    0 / 8 (0.00%)
    0 / 103 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 89 (0.00%)
    0 / 8 (0.00%)
    1 / 103 (0.97%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 May 2020
    The reason for this amendment was to make some minor corrections, remove the blood sample for cell mediated immunity (CMI) assessment at Visit 10 of proof of principle (PoP) phase to simplify study procedures, and to comply with selected recommendations from Center for Biologics Evaluation and Research (CBER). This protocol amendment 1 outlines also measures that may be applicable during special circumstances (e.g., COVID-19 pandemic), in order to protect participant’s welfare and safety and promote data integrity.
    09 Apr 2021
    The main reasons for this protocol amendment have been to simplify the study procedures for the proof of principle (PoP) phase, including those related to the screening of subjects and to outline specific measures related to an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) that may be applicable during the subjects’ participation in the study. Additionally, some minor corrections have been made as well.
    16 Jun 2021
    The sponsor is updating the clinical research phase of the study from Phase I to Phase I/II to account for the design of the study which, in its Proof of Principle epoch, aims to also generate evidence on the efficacy of the vaccine to prevent recurrences of Skin and Soft Tissue Infections due to Staphylococcus aureus in the target population.
    30 Nov 2021
    The aim of this protocol amendment is to facilitate the enrolment of subjects with S. aureus SSTIs for the PoP phase (Phase II) of the study, by extending the allowed upper age limit from 50 to 64 years, allowing enrolment of subjects with well-controlled type 2 diabetes mellitus and/or arterial hypertension, and extending the interval between S. aureus SSTI microbiological diagnosis and signature of the informed consent from 14 days to 30 days. In addition, correction of typographical error, minor edits for clarification, and the alignment of some sections to the current Company protocol template have also been made.
    22 Jun 2022
    The aim of this protocol amendment is to add that during study conduct a presentation of the placebo in a prefilled syringe (PFS) may be used. In addition, correction of typographical error, minor edits for clarification, and the alignment of some sections to the current Company protocol template have also been made.
    06 Oct 2022
    The aim of this protocol amendment is to ensure consistency across the different protocol sections related to the interim efficacy analysis, with reference to the possibility to continue the enrolment up to the planned number of events needed for the key efficacy endpoint evaluation (i.e. 27 events of recurrent S. aureus SSTI), and in case futility or efficacy criteria are met at the interim analysis based on 13 events of recurrent S. aureus SSTI. In addition, correction of typographical errors, and minor edits for clarification have been made.

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

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