Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   44366   clinical trials with a EudraCT protocol, of which   7389   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1/2a, observer-blind, randomized, controlled, two-stage, multi country study to evaluate the safety, reactogenicity, and immune response of the trivalent vaccine against invasive nontyphoidal Salmonella (iNTS) and Typhoid Fever in healthy European and African adults

    Summary
    EudraCT number
    		 2021-005178-25
    Trial protocol
    		 BE  
    Global end of trial date
    07 Jan 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jan 2026
    First version publication date
    07 Jan 2026
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    216152
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    79 New Oxford Street, London, WC1A1DG, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 044 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
    28 Feb 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Jan 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and reactogenicity profile of GSK Vaccines Institute for Global Health (GVGH) invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) vaccine in healthy European/African adults
    Protection of trial subjects
    All study activities at the study center were performed by trained clinical staff authorized by the study Investigator. The attendance of the study participants to in-person study visit posed risks that do not extend the risks associated with clinic visits for routine immunization. Considering the measures taken to minimize possible risks to the participants in this study, the potential risks associated with the study interventions and study assessments were balanced by the potential benefits that were provided to the participants. Study participants were observed for a minimum of 60 minutes after the administration of study interventions with appropriate medical attention available in case of anaphylaxis.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Sep 2022
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 5 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 50
    Country: Number of subjects enrolled
    Malawi: 105
    Worldwide total number of subjects
    155
    EEA total number of subjects
    50
    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)
    155
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 This study was conducted in Europe and Africa.

    Pre-assignment
    Screening details
    		 Stage 1: Of the 51 participants enrolled, 1 withdrew after post-screening procedures before randomization and did not receive the study intervention. Stage 2: Of the 107 participants enrolled, 2 withdrew after post-screening procedures before randomization and did not receive the study intervention

    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, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Stage 1: iNTS-TCV low dose group
    Arm description
    		 European participants were randomized to receive 3 doses of Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Experimental

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

    Investigational medicinal product name
    iNTS-TCV low dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Arm title
    		 Stage 1: iNTS-GMMA + TCV low dose group
    Arm description
    		 European participants were randomized to receive 3 doses of iNTS-Generalized modules for membrane antigens (GMMA) low dose vaccine and 3 doses of TCV low dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TCV low dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Investigational medicinal product name
    iNTS-GMMA low dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Arm title
    		 Stage 1: iNTS-TCV full dose group
    Arm description
    		 European participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Experimental

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

    Investigational medicinal product name
    iNTS-TCV full dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for suspension for injection, Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Arm title
    		 Stage 1: iNTS-GMMA + TCV full dose group
    Arm description
    		 European participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TCV full dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Investigational medicinal product name
    iNTS-GMMA full dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Arm title
    		 Stage 1: Placebo group
    Arm description
    		 European participants were randomized to receive 3 doses of Placebo and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Placebo

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

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

    Arm title
    		 Stage 2: iNTS-TCV full dose group
    Arm description
    		 African participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Placebo

    Investigational medicinal product name
    iNTS-TCV full dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

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

    Arm title
    		 Stage 2: iNTS-GMMA + TCV full dose group
    Arm description
    		 African participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose intramuscularly, in different arms, on Day 1, Day 57 and Day 169.
    Arm type
    		 Experimental

    Investigational medicinal product name
    iNTS-GMMA full dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Investigational medicinal product name
    TCV full dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses per participant

    Arm title
    		 Stage 2: Control group
    Arm description
    		 African participants were randomized to receive MENVEO as comparator and 1 dose of saline on Day 1, BOOSTRIX as comparator and 1 dose of saline on Day 57 and TYPHIM VI as comparator and 1 dose of saline on Day 169.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Menveo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant

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

    Investigational medicinal product name
    Typhim Vi
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant

    Investigational medicinal product name
    Boostrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose per participant

    Number of subjects in period 1
    		Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Started
    4
    4
    16
    16
    10
    45
    45
    15
    Completed
    4
    4
    14
    15
    10
    45
    43
    15
    Not completed
    0
    0
    2
    1
    0
    0
    2
    0
         Consent withdrawn by subject
    -
    -
    2
    1
    -
    -
    1
    -
         Not specified
    -
    -
    -
    -
    -
    -
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Stage 1: iNTS-TCV low dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-GMMA + TCV low dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-Generalized modules for membrane antigens (GMMA) low dose vaccine and 3 doses of TCV low dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-TCV full dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-GMMA + TCV full dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: Placebo group
    Reporting group description
    		 European participants were randomized to receive 3 doses of Placebo and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: iNTS-TCV full dose group
    Reporting group description
    		 African participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: iNTS-GMMA + TCV full dose group
    Reporting group description
    		 African participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: Control group
    Reporting group description
    		 African participants were randomized to receive MENVEO as comparator and 1 dose of saline on Day 1, BOOSTRIX as comparator and 1 dose of saline on Day 57 and TYPHIM VI as comparator and 1 dose of saline on Day 169.

    Reporting group values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group Total
    Number of subjects
    		 4 4 16 16 10 45 45 15 155
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 4 4 16 16 10 45 45 15 155
        From 65-84 years
    		 0 0 0 0 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 21.8 ( 2.5 ) 35.8 ( 12.0 ) 36.8 ( 11.1 ) 33.1 ( 11.3 ) 34.7 ( 9.5 ) 28.2 ( 6.3 ) 28.5 ( 6.3 ) 29.7 ( 9.1 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 4 1 11 10 10 26 23 5 90
        Male
    		 0 3 5 6 0 19 22 10 65
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 0 0 0 0 0 45 45 14 104
        White
    		 4 4 15 16 9 0 0 0 48
        American Indian or Alaska Native
    		 0 0 0 0 0 0 0 1 1
        Other
    		 0 0 1 0 1 0 0 0 2

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Stage 1: iNTS-TCV low dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-GMMA + TCV low dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-Generalized modules for membrane antigens (GMMA) low dose vaccine and 3 doses of TCV low dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-TCV full dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-GMMA + TCV full dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: Placebo group
    Reporting group description
    		 European participants were randomized to receive 3 doses of Placebo and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: iNTS-TCV full dose group
    Reporting group description
    		 African participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: iNTS-GMMA + TCV full dose group
    Reporting group description
    		 African participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: Control group
    Reporting group description
    		 African participants were randomized to receive MENVEO as comparator and 1 dose of saline on Day 1, BOOSTRIX as comparator and 1 dose of saline on Day 57 and TYPHIM VI as comparator and 1 dose of saline on Day 169.

    Primary: Stage 1: Number of participants with any solicited administration site events after the first study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any solicited administration site events after the first study intervention administration [1] [2]
    End point description
    The solicited administration site events included redness (erythema), pain, and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received first dose of the study intervention and who had solicited safety data in the 7 days following first intervention.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
    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: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
        Redness, iNTS-TCV low dose
    1
    0
    0
    0
    0
        Redness, Saline
    0
    0
    0
    0
    0
        Redness, iNTS-GMMA low dose
    0
    0
    0
    0
    0
        Redness, TCV low dose
    0
    0
    0
    0
    0
        Redness, iNTS-TCV full dose
    0
    0
    4
    0
    0
        Redness, iNTS-GMMA full dose
    0
    0
    0
    5
    0
        Redness, TCV full dose
    0
    0
    0
    0
    0
        Redness, Placebo
    0
    0
    0
    0
    0
        Pain, iNTS-TCV low dose
    4
    0
    0
    0
    0
        Pain, saline
    0
    0
    1
    0
    3
        Pain, iNTS-GMMA low dose
    0
    4
    0
    0
    0
        Pain, TCV low dose
    0
    1
    0
    0
    0
        Pain, iNTS-TCV full dose
    0
    0
    16
    0
    0
        Pain, iNTS-GMMA full dose
    0
    0
    0
    16
    0
        Pain, TCV full dose
    0
    0
    0
    1
    0
        Pain, Placebo
    0
    0
    0
    0
    3
        Swelling, iNTS-TCV Low
    1
    0
    0
    0
    0
        Swelling, saline
    0
    0
    0
    0
    0
        Swelling, TCV low dose
    0
    0
    0
    0
    0
        Swelling, iNTS-GMMA low dose
    0
    1
    0
    0
    0
        Swelling, iNTS-TCV full dose
    0
    0
    4
    0
    0
        Swelling, TCV full dose
    0
    0
    0
    0
    0
        Swelling, iNTS-GMMA full dose
    0
    0
    0
    3
    0
        Swelling, Placebo
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any solicited administration site events after the second study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any solicited administration site events after the second study intervention administration [3] [4]
    End point description
    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received second dose of the study intervention and who had solicited safety data in the 7 days following second intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    15
    15
    10
    Units: Participants
        Redness, iNTS-TCV low dose
    0
    0
    0
    0
    0
        Redness, Saline
    0
    0
    0
    0
    0
        Redness, iNTS-GMMA low dose
    0
    0
    0
    0
    0
        Redness, TCV low dose
    0
    0
    0
    0
    0
        Redness, iNTS-TCV full dose
    0
    0
    6
    0
    0
        Redness, iNTS-GMMA full dose
    0
    0
    0
    3
    0
        Redness, TCV full dose
    0
    0
    0
    0
    0
        Redness, Placebo
    0
    0
    0
    0
    0
        Pain, iNTS-TCV low dose
    4
    0
    0
    0
    0
        Pain, saline
    2
    0
    0
    0
    2
        Pain, iNTS-GMMA low dose
    0
    4
    0
    0
    0
        Pain, TCV low dose
    0
    1
    0
    0
    0
        Pain, iNTS-TCV full dose
    0
    0
    15
    0
    0
        Pain, iNTS-GMMA full dose
    0
    0
    0
    14
    0
        Pain, TCV full dose
    0
    0
    0
    7
    0
        Pain, Placebo
    0
    0
    0
    0
    5
        Swelling, iNTS-TCV Low dose
    0
    0
    0
    0
    0
        Swelling, saline
    0
    0
    0
    0
    0
        Swelling, TCV low dose
    0
    0
    0
    0
    0
        Swelling, iNTS-GMMA low dose
    0
    0
    0
    0
    0
        Swelling, iNTS-TCV full dose
    0
    0
    2
    0
    0
        Swelling, TCV full dose
    0
    0
    0
    0
    0
        Swelling, iNTS-GMMA full dose
    0
    0
    0
    1
    0
        Swelling, Placebo
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any solicited administration site events after the third study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any solicited administration site events after the third study intervention administration [5] [6]
    End point description
    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received third dose of the study intervention and who had solicited safety data in the 7 days following third intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    13
    14
    10
    Units: Participants
        Redness, iNTS-TCV low dose
    0
    0
    0
    0
    0
        Redness, Saline
    0
    0
    0
    0
    0
        Redness, iNTS-GMMA low dose
    0
    0
    0
    0
    0
        Redness, TCV low dose
    0
    0
    0
    0
    0
        Redness, iNTS-TCV full dose
    0
    0
    3
    0
    0
        Redness, iNTS-GMMA full dose
    0
    0
    0
    4
    0
        Redness, TCV full dose
    0
    0
    0
    4
    0
        Redness, Placebo
    0
    0
    0
    0
    0
        Pain, iNTS-TCV low dose
    4
    0
    0
    0
    0
        Pain, saline
    1
    0
    1
    0
    1
        Pain, iNTS-GMMA low dose
    0
    3
    0
    0
    0
        Pain, TCV low dose
    0
    0
    0
    0
    0
        Pain, iNTS-TCV full dose
    0
    0
    11
    0
    0
        Pain, iNTS-GMMA full dose
    0
    0
    0
    14
    0
        Pain, TCV full dose
    0
    0
    0
    2
    0
        Pain, Placebo
    0
    0
    0
    0
    5
        Swelling, iNTS-TCV Low
    0
    0
    0
    0
    0
        Swelling, saline
    0
    0
    0
    0
    0
        Swelling, TCV low dose
    0
    0
    0
    0
    0
        Swelling, iNTS-GMMA low dose
    0
    0
    0
    0
    0
        Swelling, iNTS-TCV full dose
    0
    0
    2
    0
    0
        Swelling, TCV full dose
    0
    0
    0
    0
    0
        Swelling, iNTS-GMMA full dose
    0
    0
    0
    1
    0
        Swelling, Placebo
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any solicited systemic events after the first study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any solicited systemic events after the first study intervention administration [7] [8]
    End point description
    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (>=) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received first dose of the study intervention and who had solicited safety data in the 7 days following first intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
        Arthralgia
    0
    1
    3
    3
    0
        Fatigue
    2
    3
    7
    11
    2
        Headache
    3
    2
    6
    5
    1
        Myalgia
    4
    2
    6
    6
    0
        Fever
    0
    0
    1
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any solicited systemic events after the second study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any solicited systemic events after the second study intervention administration [9] [10]
    End point description
    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received second dose of the study intervention and who had solicited safety data in the 7 days following second intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
    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: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    15
    15
    10
    Units: Participants
        Arthralgia
    1
    0
    1
    2
    0
        Fatigue
    2
    1
    7
    6
    1
        Headache
    1
    1
    5
    6
    0
        Myalgia
    2
    0
    4
    4
    1
        Fever
    0
    1
    2
    1
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any solicited systemic events after the third study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any solicited systemic events after the third study intervention administration [11] [12]
    End point description
    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received third dose of the study intervention and who had solicited safety data in the 7 days following third intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    13
    14
    10
    Units: Participants
        Arthralgia
    0
    1
    1
    2
    0
        Fatigue
    0
    1
    4
    7
    0
        Headache
    0
    1
    3
    7
    3
        Myalgia
    1
    1
    5
    10
    0
        Fever
    0
    0
    1
    1
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any unsolicited adverse events (AE) after the first study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any unsolicited adverse events (AE) after the first study intervention administration [13] [14]
    End point description
    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the unsolicited safety set, which included all participants who received the first dose of the study intervention and reported having/not having unsolicited AEs during the specified timepoints.
    End point type
    Primary
    End point timeframe
    Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
    4
    2
    14
    13
    4
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any unsolicited AEs after the second study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any unsolicited AEs after the second study intervention administration [15] [16]
    End point description
    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the unsolicited safety set, which included all participants who received the second dose of the study intervention and reported having/not having unsolicited AEs during the specified timepoints.
    End point type
    Primary
    End point timeframe
    Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)
    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: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    15
    15
    10
    Units: Participants
    3
    1
    8
    8
    2
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any unsolicited AEs after the third study intervention administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any unsolicited AEs after the third study intervention administration [17] [18]
    End point description
    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the unsolicited safety set, which included all participants who received the third dose of the study intervention and reported having/not having unsolicited AEs during the specified timepoints. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    13
    14
    10
    Units: Participants
    0
    1
    3
    5
    5
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants with any Serious AEs (SAEs)

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with any Serious AEs (SAEs) [19] [20]
    End point description
    An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set, which included all participants who received at least 1 dose of the study intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
    0
    0
    0
    1
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants with any AEs/SAEs Leading to Withdrawal from the Study

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants with any AEs/SAEs Leading to Withdrawal from the Study [21] [22]
    End point description
    A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for him/her since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants with any AEs/SAEs Leading to Withholding Further Study Intervention Administration

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants with any AEs/SAEs Leading to Withholding Further Study Intervention Administration [23] [24]
    End point description
    An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement. An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. AEs/SAEs that lead to withholding of the study intervention administration were considered under this outcome measure. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
    0
    0
    1
    1
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 8

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 8 [25] [26]
    End point description
    Assessed hepatic laboratory parameters included alanine aminotransferase [ALT] and aspartate aminotransferase [AST], and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 8 (7 days after the first study intervention administration) 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [26] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
        ALT|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        AST|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - below (Day 8)
    0
    2
    0
    0
    0
        ALT|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        AST|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Platelets|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        WBC|Within (baseline) - below (Day 8)
    0
    0
    0
    0
    1
        ALT|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        AST|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - below (Day 8)
    0
    0
    0
    0
    0
        ALT|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        AST|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 8)
    0
    0
    1
    1
    0
        Basophils|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - within (Day 8)
    0
    1
    0
    0
    0
        WBC|Below (baseline) - within (Day 8)
    1
    0
    0
    0
    0
        ALT|Within (baseline) - within (Day 8)
    4
    4
    13
    16
    10
        AST|Within (baseline) - within (Day 8)
    3
    4
    14
    16
    9
        Creatinine|Within (baseline) - within (Day 8)
    2
    3
    14
    13
    8
        Urea Nitrogen|Within (baseline) - within (Day 8)
    4
    4
    15
    15
    10
        Basophils|Within (baseline) - within (Day 8)
    4
    4
    16
    16
    10
        Eosinophils|Within (baseline) - within (Day 8)
    4
    4
    15
    16
    10
        Hemoglobin|Within (baseline) - within (Day 8)
    4
    4
    16
    16
    9
        Lymphocytes|Within (baseline) - within (Day 8)
    4
    4
    15
    15
    10
        Monocytes|Within (baseline) - within (Day 8)
    4
    4
    15
    16
    10
        Neutrophils|Within (baseline) - within (Day 8)
    3
    4
    12
    15
    9
        Platelets|Within (baseline) - within (Day 8)
    3
    3
    11
    15
    10
        WBC|Within (baseline) - within (Day 8)
    3
    2
    15
    16
    9
        ALT|Above (baseline) - within (Day 8)
    0
    0
    1
    0
    0
        AST|Above (baseline) - within (Day 8)
    1
    0
    0
    0
    1
        Creatinine|Above (baseline) - within (Day 8)
    1
    0
    0
    1
    0
        Urea Nitrogen|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 8)
    1
    0
    3
    1
    0
        Platelets|Above (baseline) - within (Day 8)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - within (Day 8)
    0
    0
    1
    0
    0
        ALT|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        AST|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        AST|Within (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - above (Day 8)
    0
    1
    1
    1
    2
        Urea Nitrogen|Within (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 8)
    0
    0
    1
    0
    0
        Hemoglobin|Within (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - above (Day 8)
    0
    0
    0
    1
    0
        Monocytes|Within (baseline) - above (Day 8)
    0
    0
    1
    0
    0
        Neutrophils|Within (baseline) - above (Day 8)
    0
    0
    1
    0
    1
        Platelets|Within (baseline) - above (Day 8)
    0
    0
    5
    1
    0
        WBC|Within (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        ALT|Above (baseline) - above (Day 8)
    0
    0
    2
    0
    0
        AST|Above (baseline) - above (Day 8)
    0
    0
    2
    0
    0
        Creatinine|Above (baseline) - above (Day 8)
    1
    0
    1
    1
    0
        Urea Nitrogen|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    1
        Lymphocytes|Above (baseline) - above (Day 8)
    0
    0
    1
    0
    0
        Monocytes|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - above (Day 8)
    1
    0
    0
    0
    0
        WBC|Above (baseline) - above (Day 8)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 64

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 64 [27] [28]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [28] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    15
    15
    10
    Units: Participants
        ALT|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        AST|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - below (Day 64)
    0
    1
    0
    0
    0
        ALT|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        AST|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Platelets|Within (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        WBC|Within (baseline) - below (Day 64)
    1
    0
    1
    0
    0
        ALT|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        AST|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - below (Day 64)
    0
    0
    0
    0
    0
        ALT|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        AST|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 64)
    1
    0
    0
    0
    0
        Basophils|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    1
        Lymphocytes|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - within (Day 64)
    0
    1
    0
    0
    0
        WBC|Below (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - within (Day 64)
    4
    4
    12
    14
    10
        AST|Within (baseline) - within (Day 64)
    2
    4
    13
    14
    10
        Creatinine|Within (baseline) - within (Day 64)
    3
    4
    14
    13
    7
        Urea Nitrogen|Within (baseline) - within (Day 64)
    3
    4
    15
    14
    10
        Basophils|Within (baseline) - within (Day 64)
    4
    4
    15
    15
    10
        Eosinophils|Within (baseline) - within (Day 64)
    4
    4
    15
    15
    10
        Hemoglobin|Within (baseline) - within (Day 64)
    4
    4
    15
    15
    9
        Lymphocytes|Within (baseline) - within (Day 64)
    4
    4
    15
    15
    9
        Monocytes|Within (baseline) - within (Day 64)
    4
    4
    15
    15
    10
        Neutrophils|Within (baseline) - within (Day 64)
    3
    4
    11
    14
    6
        Platelets|Within (baseline) - within (Day 64)
    3
    3
    13
    13
    10
        WBC|Within (baseline) - within (Day 64)
    3
    3
    14
    15
    7
        ALT|Above (baseline) - within (Day 64)
    0
    0
    2
    0
    0
        AST|Above (baseline) - within (Day 64)
    1
    0
    1
    1
    0
        Creatinine|Above (baseline) - within (Day 64)
    0
    0
    0
    1
    2
        Urea Nitrogen|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 64)
    0
    0
    1
    1
    2
        Platelets|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - within (Day 64)
    0
    0
    0
    0
    2
        ALT|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        AST|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - above (Day 64)
    0
    0
    0
    1
    0
        AST|Within (baseline) - above (Day 64)
    1
    0
    0
    0
    0
        Creatinine|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    1
        Urea Nitrogen|Within (baseline) - above (Day 64)
    0
    0
    0
    1
    0
        Basophils|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    1
        Monocytes|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - above (Day 64)
    1
    0
    2
    0
    0
        Platelets|Within (baseline) - above (Day 64)
    0
    0
    1
    2
    0
        WBC|Within (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        ALT|Above (baseline) - above (Day 64)
    0
    0
    1
    0
    0
        AST|Above (baseline) - above (Day 64)
    0
    0
    1
    0
    0
        Creatinine|Above (baseline) - above (Day 64)
    1
    0
    1
    1
    0
        Urea Nitrogen|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 64)
    0
    0
    1
    0
    2
        Platelets|Above (baseline) - above (Day 64)
    1
    0
    1
    0
    0
        WBC|Above (baseline) - above (Day 64)
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 176

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 176 [29] [30]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 176 (7 days after the third study intervention administration) compared to Baseline (Day 169)
    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 this 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    13
    14
    10
    Units: Participants
        ALT|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        AST|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - below (Day 176)
    1
    0
    0
    0
    0
        Basophils|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        AST|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Platelets|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        WBC|Within (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        ALT|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        AST|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - below (Day 176)
    0
    0
    0
    0
    0
        ALT|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        AST|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 176)
    0
    0
    0
    1
    0
        Lymphocytes|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - within (Day 176)
    0
    0
    0
    1
    0
        WBC|Below (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - within (Day 176)
    4
    3
    11
    13
    10
        AST|Within (baseline) - within (Day 176)
    4
    3
    12
    14
    10
        Creatinine|Within (baseline) - within (Day 176)
    3
    3
    10
    10
    6
        Urea Nitrogen|Within (baseline) - within (Day 176)
    3
    3
    13
    13
    10
        Basophils|Within (baseline) - within (Day 176)
    4
    3
    13
    14
    10
        Eosinophils|Within (baseline) - within (Day 176)
    4
    3
    12
    14
    10
        Hemoglobin|Within (baseline) - within (Day 176)
    4
    3
    13
    13
    9
        Lymphocytes|Within (baseline) - within (Day 176)
    4
    3
    13
    14
    10
        Monocytes|Within (baseline) - within (Day 176)
    4
    3
    13
    14
    10
        Neutrophils|Within (baseline) - within (Day 176)
    1
    3
    8
    11
    8
        Platelets|Within (baseline) - within (Day 176)
    2
    3
    9
    12
    10
        WBC|Within (baseline) - within (Day 176)
    4
    3
    13
    12
    9
        ALT|Above (baseline) - within (Day 176)
    0
    0
    1
    0
    0
        AST|Above (baseline) - within (Day 176)
    0
    0
    1
    0
    0
        Creatinine|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    1
        Urea Nitrogen|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 176)
    1
    0
    2
    1
    1
        Platelets|Above (baseline) - within (Day 176)
    0
    0
    1
    0
    0
        WBC|Above (baseline) - within (Day 176)
    0
    0
    0
    1
    0
        ALT|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        AST|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - above (Day 176)
    0
    0
    1
    1
    0
        AST|Within (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - above (Day 176)
    0
    0
    2
    3
    2
        Urea Nitrogen|Within (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 176)
    0
    0
    1
    0
    0
        Hemoglobin|Within (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - above (Day 176)
    2
    0
    2
    1
    1
        Platelets|Within (baseline) - above (Day 176)
    2
    0
    2
    1
    0
        WBC|Within (baseline) - above (Day 176)
    0
    0
    0
    1
    1
        ALT|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        AST|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - above (Day 176)
    1
    0
    1
    1
    1
        Urea Nitrogen|Above (baseline) - above (Day 176)
    0
    0
    0
    1
    0
        Basophils|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    1
        Lymphocytes|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 176)
    0
    0
    1
    1
    0
        Platelets|Above (baseline) - above (Day 176)
    0
    0
    1
    0
    0
        WBC|Above (baseline) - above (Day 176)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 29

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 29 [31] [32]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [32] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: Participants
        ALT|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        AST|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - below (Day 29)
    0
    1
    0
    0
    0
        ALT|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        AST|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Platelets|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        WBC|Within (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        ALT|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        AST|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - below (Day 29)
    0
    0
    0
    0
    0
        ALT|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        AST|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 29)
    0
    0
    1
    1
    0
        Basophils|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - within (Day 29)
    0
    1
    0
    0
    0
        WBC|Below (baseline) - within (Day 29)
    1
    1
    0
    0
    0
        ALT|Within (baseline) - within (Day 29)
    4
    4
    13
    16
    10
        AST|Within (baseline) - within (Day 29)
    3
    4
    14
    16
    9
        Creatinine|Within (baseline) - within (Day 29)
    2
    4
    15
    14
    8
        Urea Nitrogen|Within (baseline) - within (Day 29)
    4
    4
    15
    15
    10
        Basophils|Within (baseline) - within (Day 29)
    4
    4
    16
    16
    10
        Eosinophils|Within (baseline) - within (Day 29)
    4
    4
    15
    16
    10
        Hemoglobin|Within (baseline) - within (Day 29)
    4
    4
    16
    15
    9
        Lymphocytes|Within (baseline) - within (Day 29)
    4
    4
    15
    16
    10
        Monocytes|Within (baseline) - within (Day 29)
    4
    4
    16
    15
    10
        Neutrophils|Within (baseline) - within (Day 29)
    3
    4
    12
    14
    9
        Platelets|Within (baseline) - within (Day 29)
    2
    3
    14
    16
    10
        WBC|Within (baseline) - within (Day 29)
    3
    2
    14
    15
    10
        ALT|Above (baseline) - within (Day 29)
    0
    0
    1
    0
    0
        AST|Above (baseline) - within (Day 29)
    1
    0
    2
    0
    1
        Creatinine|Above (baseline) - within (Day 29)
    1
    0
    0
    2
    0
        Urea Nitrogen|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 29)
    0
    0
    1
    1
    0
        Platelets|Above (baseline) - within (Day 29)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - within (Day 29)
    0
    0
    1
    0
    0
        ALT|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        AST|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        AST|Within (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - above (Day 29)
    0
    0
    0
    0
    2
        Urea Nitrogen|Within (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 29)
    0
    0
    1
    0
    0
        Hemoglobin|Within (baseline) - above (Day 29)
    0
    0
    0
    1
    0
        Lymphocytes|Within (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - above (Day 29)
    0
    0
    0
    1
    0
        Neutrophils|Within (baseline) - above (Day 29)
    0
    0
    1
    1
    1
        Platelets|Within (baseline) - above (Day 29)
    1
    0
    2
    0
    0
        WBC|Within (baseline) - above (Day 29)
    0
    0
    1
    1
    0
        ALT|Above (baseline) - above (Day 29)
    0
    0
    2
    0
    0
        AST|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - above (Day 29)
    1
    0
    1
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    1
        Lymphocytes|Above (baseline) - above (Day 29)
    0
    0
    1
    0
    0
        Monocytes|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 29)
    1
    0
    2
    0
    0
        Platelets|Above (baseline) - above (Day 29)
    1
    0
    0
    0
    0
        WBC|Above (baseline) - above (Day 29)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 85

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 85 [33] [34]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [34] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    15
    15
    10
    Units: Participants
        ALT|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        AST|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - below (Day 85)
    0
    1
    0
    0
    0
        WBC|Below (baseline) - below (Day 85)
    0
    1
    0
    0
    0
        ALT|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        AST|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 85)
    0
    0
    0
    1
    0
        Lymphocytes|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Platelets|Within (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        WBC|Within (baseline) - below (Day 85)
    0
    1
    0
    0
    0
        ALT|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        AST|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - below (Day 85)
    0
    0
    0
    0
    0
        ALT|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        AST|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 85)
    1
    0
    0
    0
    0
        Basophils|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    1
        Lymphocytes|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - within (Day 85)
    4
    4
    11
    15
    10
        AST|Within (baseline) - within (Day 85)
    3
    4
    13
    13
    10
        Creatinine|Within (baseline) - within (Day 85)
    3
    4
    12
    11
    7
        Urea Nitrogen|Within (baseline) - within (Day 85)
    3
    4
    15
    15
    10
        Basophils|Within (baseline) - within (Day 85)
    4
    4
    15
    15
    10
        Eosinophils|Within (baseline) - within (Day 85)
    4
    4
    15
    15
    10
        Hemoglobin|Within (baseline) - within (Day 85)
    4
    4
    15
    14
    9
        Lymphocytes|Within (baseline) - within (Day 85)
    4
    4
    15
    14
    10
        Monocytes|Within (baseline) - within (Day 85)
    4
    4
    15
    15
    10
        Neutrophils|Within (baseline) - within (Day 85)
    4
    4
    13
    14
    6
        Platelets|Within (baseline) - within (Day 85)
    3
    3
    13
    15
    10
        WBC|Within (baseline) - within (Day 85)
    4
    2
    15
    14
    7
        ALT|Above (baseline) - within (Day 85)
    0
    0
    2
    0
    0
        AST|Above (baseline) - within (Day 85)
    1
    0
    2
    1
    0
        Creatinine|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    1
        Urea Nitrogen|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    4
        Platelets|Above (baseline) - within (Day 85)
    0
    0
    1
    0
    0
        WBC|Above (baseline) - within (Day 85)
    0
    0
    0
    0
    3
        ALT|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        AST|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - above (Day 85)
    0
    0
    1
    0
    0
        AST|Within (baseline) - above (Day 85)
    0
    0
    0
    1
    0
        Creatinine|Within (baseline) - above (Day 85)
    0
    0
    2
    2
    1
        Urea Nitrogen|Within (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Lymphocytes|Within (baseline) - above (Day 85)
    0
    0
    0
    1
    0
        Monocytes|Within (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Platelets|Within (baseline) - above (Day 85)
    0
    0
    1
    0
    0
        WBC|Within (baseline) - above (Day 85)
    0
    0
    0
    1
    0
        ALT|Above (baseline) - above (Day 85)
    0
    0
    1
    0
    0
        AST|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - above (Day 85)
    1
    0
    1
    2
    1
        Urea Nitrogen|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 85)
    0
    0
    2
    1
    0
        Platelets|Above (baseline) - above (Day 85)
    1
    0
    0
    0
    0
        WBC|Above (baseline) - above (Day 85)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 197

    		 Close Top of page
    End point title
    		 Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 197 [35] [36]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [36] - 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: <The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    13
    14
    10
    Units: Participants
        ALT|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        AST|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - below (Day 197)
    0
    0
    0
    1
    0
        WBC|Below (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        AST|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 197)
    0
    0
    1
    1
    0
        Lymphocytes|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 197)
    0
    0
    1
    0
    0
        Platelets|Within (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        WBC|Within (baseline) - below (Day 197)
    0
    1
    1
    0
    0
        ALT|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        AST|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        Platelets|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        WBC|Above (baseline) - below (Day 197)
    0
    0
    0
    0
    0
        ALT|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        AST|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 197)
    1
    0
    0
    0
    0
        Basophils|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - within (Day 197)
    4
    3
    10
    14
    10
        AST|Within (baseline) - within (Day 197)
    4
    3
    12
    13
    10
        Creatinine|Within (baseline) - within (Day 197)
    2
    3
    11
    13
    7
        Urea Nitrogen|Within (baseline) - within (Day 197)
    3
    3
    13
    13
    10
        Basophils|Within (baseline) - within (Day 197)
    4
    3
    13
    14
    10
        Eosinophils|Within (baseline) - within (Day 197)
    4
    3
    13
    14
    10
        Hemoglobin|Within (baseline) - within (Day 197)
    4
    3
    11
    12
    9
        Lymphocytes|Within (baseline) - within (Day 197)
    4
    3
    13
    13
    10
        Monocytes|Within (baseline) - within (Day 197)
    4
    3
    13
    14
    10
        Neutrophils|Within (baseline) - within (Day 197)
    3
    3
    9
    11
    9
        Platelets|Within (baseline) - within (Day 197)
    3
    2
    11
    13
    10
        WBC|Within (baseline) - within (Day 197)
    4
    2
    12
    12
    10
        ALT|Above (baseline) - within (Day 197)
    0
    0
    1
    0
    0
        AST|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Creatinine|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Basophils|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Lymphocytes|Above (baseline) - within (Day 197)
    0
    0
    0
    1
    0
        Monocytes|Above (baseline) - within (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 197)
    1
    0
    2
    1
    0
        Platelets|Above (baseline) - within (Day 197)
    0
    0
    1
    0
    0
        WBC|Above (baseline) - within (Day 197)
    0
    0
    0
    1
    0
        ALT|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        AST|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Basophils|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Platelets|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        WBC|Below (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        ALT|Within (baseline) - above (Day 197)
    0
    0
    2
    0
    0
        AST|Within (baseline) - above (Day 197)
    0
    0
    0
    1
    0
        Creatinine|Within (baseline) - above (Day 197)
    1
    0
    1
    0
    1
        Urea Nitrogen|Within (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Basophils|Within (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 197)
    0
    0
    1
    1
    0
        Lymphocytes|Within (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Within (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Within (baseline) - above (Day 197)
    0
    0
    0
    1
    0
        Platelets|Within (baseline) - above (Day 197)
    1
    1
    0
    0
    0
        WBC|Within (baseline) - above (Day 197)
    0
    0
    0
    1
    0
        ALT|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        AST|Above (baseline) - above (Day 197)
    0
    0
    1
    0
    0
        Creatinine|Above (baseline) - above (Day 197)
    1
    0
    1
    1
    2
        Urea Nitrogen|Above (baseline) - above (Day 197)
    0
    0
    0
    1
    0
        Basophils|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    1
        Lymphocytes|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 197)
    0
    0
    1
    1
    1
        Platelets|Above (baseline) - above (Day 197)
    0
    0
    1
    0
    0
        WBC|Above (baseline) - above (Day 197)
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any solicited administration site events after the first study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any solicited administration site events after the first study intervention administration [37] [38]
    End point description
    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received first dose of the study intervention and who had solicited safety data in the 7 days following first intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
    Notes
    [37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [38] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
        Redness, iNTS-TCV full dose
    2
    0
    0
        Redness, saline
    0
    0
    0
        Redness, TCV full dose
    0
    3
    0
        Redness, iNTS-GMMA full dose
    0
    7
    0
        Redness, control
    0
    0
    0
        Pain, iNTS-TCV full dose
    38
    0
    0
        Pain, saline
    16
    0
    5
        Pain, TCV full dose
    0
    20
    0
        Pain, iNTS-GMMA full dose
    0
    41
    0
        Pain, control
    0
    0
    6
        Swelling, iNTS-TCV full dose
    7
    0
    0
        Swelling, saline
    1
    0
    0
        Swelling, TCV full dose
    0
    2
    0
        Swelling, iNTS-GMMA full dose
    0
    10
    0
        Swelling, control
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any solicited administration site events after the second study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any solicited administration site events after the second study intervention administration [39] [40]
    End point description
    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received second dose of the study intervention and who had solicited safety data in the 7 days following second intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
    Notes
    [39] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [40] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    43
    15
    Units: Participants
        Redness, iNTS-TCV full dose
    1
    0
    0
        Redness, saline
    1
    0
    0
        Redness, TCV full dose
    0
    2
    0
        Redness, iNTS-GMMA full dose
    0
    3
    0
        Redness, control
    0
    0
    1
        Pain, iNTS-TCV full dose
    35
    0
    0
        Pain, saline
    14
    0
    5
        Pain, TCV full dose
    0
    24
    0
        Pain, iNTS-GMMA full dose
    0
    41
    0
        Pain, control
    0
    0
    9
        Swelling, iNTS-TCV full dose
    6
    0
    0
        Swelling, saline
    2
    0
    0
        Swelling, TCV full dose
    0
    6
    0
        Swelling, iNTS-GMMA full dose
    0
    11
    0
        Swelling, control
    0
    0
    2
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any solicited administration site events after the third study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any solicited administration site events after the third study intervention administration [41] [42]
    End point description
    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received third dose of the study intervention and who had solicited safety data in the 7 days following third intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
    Notes
    [41] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [42] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    42
    38
    14
    Units: Participants
        Redness, iNTS-TCV full dose
    4
    0
    0
        Redness, saline
    0
    0
    0
        Redness, TCV full dose
    0
    1
    0
        Redness, iNTS-GMMA full dose
    0
    3
    0
        Redness, control
    0
    0
    0
        Pain, iNTS-TCV full dose
    32
    0
    0
        Pain, saline
    10
    0
    6
        Pain, TCV full dose
    0
    19
    0
        Pain, iNTS-GMMA full dose
    0
    35
    0
        Pain, control
    0
    0
    8
        Swelling, iNTS-TCV full dose
    5
    0
    0
        Swelling, saline
    2
    0
    1
        Swelling, TCV full dose
    0
    2
    0
        Swelling, iNTS-GMMA full dose
    0
    9
    0
        Swelling, control
    0
    0
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any solicited systemic events after the first study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any solicited systemic events after the first study intervention administration [43] [44]
    End point description
    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature >=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received first dose of the study intervention and who had solicited safety data in the 7 days following first intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
    Notes
    [43] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [44] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
        Arthralgia
    12
    10
    3
        Fatigue
    23
    20
    4
        Headache
    26
    24
    5
        Myalgia
    23
    21
    3
        Fever
    8
    6
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any solicited systemic events after the second study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any solicited systemic events after the second study intervention administration [45] [46]
    End point description
    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature >=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received second dose of the study intervention and who had solicited safety data in the 7 days following second intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
    Notes
    [45] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [46] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    43
    15
    Units: Participants
        Arthralgia
    11
    11
    5
        Fatigue
    18
    24
    4
        Headache
    22
    26
    5
        Myalgia
    18
    20
    5
        Fever
    5
    5
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any solicited systemic events after the third study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any solicited systemic events after the third study intervention administration [47] [48]
    End point description
    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature >=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the Solicited safety set, which included all participants who received third dose of the study intervention and who had solicited safety data in the 7 days following third intervention. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
    Notes
    [47] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [48] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    42
    38
    14
    Units: Participants
        Arthralgia
    13
    15
    3
        Fatigue
    18
    18
    2
        Headache
    21
    23
    2
        Myalgia
    17
    18
    4
        Fever
    4
    9
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any unsolicited AE after the first study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any unsolicited AE after the first study intervention administration [49] [50]
    End point description
    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the unsolicited safety set, which included all participants who received the first dose of the study intervention and reported having/not having unsolicited AEs during the specified timepoints. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)
    Notes
    [49] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [50] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
    21
    24
    8
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any unsolicited AE after the second study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any unsolicited AE after the second study intervention administration [51] [52]
    End point description
    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the unsolicited safety set, which included all participants who received the second dose of the study intervention and reported having/not having unsolicited AEs during the specified timepoints. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)
    Notes
    [51] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [52] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    43
    15
    Units: Participants
    13
    17
    3
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any unsolicited AE after the third study intervention administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any unsolicited AE after the third study intervention administration [53] [54]
    End point description
    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the unsolicited safety set, which included all participants who received the third dose of the study intervention and reported having/not having unsolicited AEs during the specified timepoints. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)
    Notes
    [53] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [54] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    42
    38
    14
    Units: Participants
    13
    12
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants with any SAEs

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with any SAEs [55] [56]
    End point description
    An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
    Notes
    [55] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [56] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
    0
    1
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants with any AEs/SAEs Leading to Withdrawal from the Study

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants with any AEs/SAEs Leading to Withdrawal from the Study [57] [58]
    End point description
    Any AEs including SAEs that lead to withdrawal from the study are considered under this outcome measure. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for him/her since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)
    Notes
    [57] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [58] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants with any AEs/SAEs Leading to Withholding Further Study Intervention Administration

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants with any AEs/SAEs Leading to Withholding Further Study Intervention Administration [59] [60]
    End point description
    AEs/SAEs that lead to withholding of the study intervention administration were considered under this outcome measure. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)
    Notes
    [59] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [60] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 8

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 8 [61] [62]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 8 (7 days after the first study intervention administration) compared to Baseline (Day 1)
    Notes
    [61] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [62] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
        ALT|Below (baseline) - below (Day 8)
    0
    0
    0
        AST|Below (baseline) - below (Day 8)
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 8)
    2
    3
    0
        Urea Nitrogen|Below (baseline) - below (Day 8)
    6
    5
    1
        Basophils|Below (baseline) - below (Day 8)
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 8)
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 8)
    1
    0
    0
        Lymphocytes|Below (baseline) - below (Day 8)
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 8)
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 8)
    0
    0
    0
        Platelets|Below (baseline) - below (Day 8)
    1
    0
    0
        WBC|Below (baseline) - below (Day 8)
    0
    0
    0
        ALT|Within (baseline) - below (Day 8)
    2
    1
    0
        AST|Within (baseline) - below (Day 8)
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 8)
    1
    1
    1
        Urea Nitrogen|Within (baseline) - below (Day 8)
    11
    4
    0
        Basophils|Within (baseline) - below (Day 8)
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 8)
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 8)
    1
    1
    0
        Lymphocytes|Within (baseline) - below (Day 8)
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 8)
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 8)
    0
    0
    0
        Platelets|Within (baseline) - below (Day 8)
    0
    0
    0
        WBC|Within (baseline) - below (Day 8)
    0
    1
    0
        ALT|Above (baseline) - below (Day 8)
    0
    0
    0
        AST|Above (baseline) - below (Day 8)
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 8)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 8)
    0
    0
    0
        Basophils|Above (baseline) - below (Day 8)
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 8)
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 8)
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 8)
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 8)
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 8)
    0
    0
    0
        Platelets|Above (baseline) - below (Day 8)
    0
    0
    0
        WBC|Above (baseline) - below (Day 8)
    0
    0
    0
        ALT|Below (baseline) - within (Day 8)
    0
    0
    0
        AST|Below (baseline) - within (Day 8)
    1
    0
    0
        Creatinine|Below (baseline) - within (Day 8)
    1
    0
    1
        Urea Nitrogen|Below (baseline) - within (Day 8)
    6
    7
    3
        Basophils|Below (baseline) - within (Day 8)
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 8)
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 8)
    0
    0
    0
        Lymphocytes|Below (baseline) - within (Day 8)
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 8)
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 8)
    0
    0
    0
        Platelets|Below (baseline) - within (Day 8)
    0
    1
    0
        WBC|Below (baseline) - within (Day 8)
    0
    0
    0
        ALT|Within (baseline) - within (Day 8)
    36
    35
    13
        AST|Within (baseline) - within (Day 8)
    37
    43
    12
        Creatinine|Within (baseline) - within (Day 8)
    41
    41
    13
        Urea Nitrogen|Within (baseline) - within (Day 8)
    22
    29
    11
        Basophils|Within (baseline) - within (Day 8)
    45
    44
    15
        Eosinophils|Within (baseline) - within (Day 8)
    44
    45
    15
        Hemoglobin|Within (baseline) - within (Day 8)
    38
    39
    11
        Lymphocytes|Within (baseline) - within (Day 8)
    43
    43
    13
        Monocytes|Within (baseline) - within (Day 8)
    39
    44
    15
        Neutrophils|Within (baseline) - within (Day 8)
    41
    42
    15
        Platelets|Within (baseline) - within (Day 8)
    35
    32
    11
        WBC|Within (baseline) - within (Day 8)
    41
    41
    14
        ALT|Above (baseline) - within (Day 8)
    3
    5
    2
        AST|Above (baseline) - within (Day 8)
    2
    2
    3
        Creatinine|Above (baseline) - within (Day 8)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 8)
    0
    0
    0
        Basophils|Above (baseline) - within (Day 8)
    0
    1
    0
        Eosinophils|Above (baseline) - within (Day 8)
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 8)
    1
    2
    0
        Lymphocytes|Above (baseline) - within (Day 8)
    0
    0
    2
        Monocytes|Above (baseline) - within (Day 8)
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 8)
    1
    1
    0
        Platelets|Above (baseline) - within (Day 8)
    0
    1
    1
        WBC|Above (baseline) - within (Day 8)
    0
    2
    1
        ALT|Below (baseline) - above (Day 8)
    0
    0
    0
        AST|Below (baseline) - above (Day 8)
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 8)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 8)
    0
    0
    0
        Basophils|Below (baseline) - above (Day 8)
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 8)
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 8)
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 8)
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 8)
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 8)
    0
    0
    0
        Platelets|Below (baseline) - above (Day 8)
    0
    0
    0
        WBC|Below (baseline) - above (Day 8)
    0
    0
    0
        ALT|Within (baseline) - above (Day 8)
    2
    2
    0
        AST|Within (baseline) - above (Day 8)
    3
    0
    0
        Creatinine|Within (baseline) - above (Day 8)
    0
    0
    0
        Urea Nitrogen|Within (baseline) - above (Day 8)
    0
    0
    0
        Basophils|Within (baseline) - above (Day 8)
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 8)
    1
    0
    0
        Hemoglobin|Within (baseline) - above (Day 8)
    1
    1
    2
        Lymphocytes|Within (baseline) - above (Day 8)
    1
    2
    0
        Monocytes|Within (baseline) - above (Day 8)
    6
    1
    0
        Neutrophils|Within (baseline) - above (Day 8)
    3
    1
    0
        Platelets|Within (baseline) - above (Day 8)
    5
    5
    1
        WBC|Within (baseline) - above (Day 8)
    3
    1
    0
        ALT|Above (baseline) - above (Day 8)
    2
    2
    0
        AST|Above (baseline) - above (Day 8)
    2
    0
    0
        Creatinine|Above (baseline) - above (Day 8)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 8)
    0
    0
    0
        Basophils|Above (baseline) - above (Day 8)
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 8)
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 8)
    3
    2
    2
        Lymphocytes|Above (baseline) - above (Day 8)
    1
    0
    0
        Monocytes|Above (baseline) - above (Day 8)
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 8)
    0
    1
    0
        Platelets|Above (baseline) - above (Day 8)
    4
    6
    2
        WBC|Above (baseline) - above (Day 8)
    1
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 64

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 64 [63] [64]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)
    Notes
    [63] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [64] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    43
    15
    Units: Participants
        ALT|Below (baseline) - below (Day 64)
    0
    0
    0
        AST|Below (baseline) - below (Day 64)
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 64)
    3
    3
    0
        Urea Nitrogen|Below (baseline) - below (Day 64)
    6
    5
    4
        Basophils|Below (baseline) - below (Day 64)
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 64)
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 64)
    1
    0
    0
        Lymphocytes|Below (baseline) - below (Day 64)
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 64)
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 64)
    0
    0
    0
        Platelets|Below (baseline) - below (Day 64)
    1
    0
    0
        WBC|Below (baseline) - below (Day 64)
    0
    0
    0
        ALT|Within (baseline) - below (Day 64)
    1
    1
    0
        AST|Within (baseline) - below (Day 64)
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 64)
    1
    2
    0
        Urea Nitrogen|Within (baseline) - below (Day 64)
    4
    8
    1
        Basophils|Within (baseline) - below (Day 64)
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 64)
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 64)
    0
    1
    0
        Lymphocytes|Within (baseline) - below (Day 64)
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 64)
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 64)
    0
    1
    0
        Platelets|Within (baseline) - below (Day 64)
    0
    0
    0
        WBC|Within (baseline) - below (Day 64)
    1
    0
    0
        ALT|Above (baseline) - below (Day 64)
    0
    0
    0
        AST|Above (baseline) - below (Day 64)
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 64)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 64)
    0
    0
    0
        Basophils|Above (baseline) - below (Day 64)
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 64)
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 64)
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 64)
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 64)
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 64)
    0
    0
    0
        Platelets|Above (baseline) - below (Day 64)
    0
    0
    0
        WBC|Above (baseline) - below (Day 64)
    0
    0
    0
        ALT|Below (baseline) - within (Day 64)
    1
    0
    0
        AST|Below (baseline) - within (Day 64)
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 64)
    0
    4
    1
        Urea Nitrogen|Below (baseline) - within (Day 64)
    9
    2
    2
        Basophils|Below (baseline) - within (Day 64)
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 64)
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 64)
    1
    0
    0
        Lymphocytes|Below (baseline) - within (Day 64)
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 64)
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 64)
    0
    0
    0
        Platelets|Below (baseline) - within (Day 64)
    0
    0
    0
        WBC|Below (baseline) - within (Day 64)
    0
    0
    0
        ALT|Within (baseline) - within (Day 64)
    38
    35
    12
        AST|Within (baseline) - within (Day 64)
    40
    39
    11
        Creatinine|Within (baseline) - within (Day 64)
    41
    34
    14
        Urea Nitrogen|Within (baseline) - within (Day 64)
    26
    28
    8
        Basophils|Within (baseline) - within (Day 64)
    44
    43
    15
        Eosinophils|Within (baseline) - within (Day 64)
    40
    43
    15
        Hemoglobin|Within (baseline) - within (Day 64)
    37
    37
    13
        Lymphocytes|Within (baseline) - within (Day 64)
    43
    42
    15
        Monocytes|Within (baseline) - within (Day 64)
    44
    41
    15
        Neutrophils|Within (baseline) - within (Day 64)
    41
    39
    15
        Platelets|Within (baseline) - within (Day 64)
    34
    35
    12
        WBC|Within (baseline) - within (Day 64)
    40
    41
    15
        ALT|Above (baseline) - within (Day 64)
    2
    4
    0
        AST|Above (baseline) - within (Day 64)
    1
    4
    0
        Creatinine|Above (baseline) - within (Day 64)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 64)
    0
    0
    0
        Basophils|Above (baseline) - within (Day 64)
    1
    0
    0
        Eosinophils|Above (baseline) - within (Day 64)
    1
    0
    0
        Hemoglobin|Above (baseline) - within (Day 64)
    1
    2
    0
        Lymphocytes|Above (baseline) - within (Day 64)
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 64)
    1
    1
    0
        Neutrophils|Above (baseline) - within (Day 64)
    2
    1
    0
        Platelets|Above (baseline) - within (Day 64)
    1
    0
    0
        WBC|Above (baseline) - within (Day 64)
    2
    0
    0
        ALT|Below (baseline) - above (Day 64)
    0
    0
    0
        AST|Below (baseline) - above (Day 64)
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 64)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 64)
    0
    0
    0
        Basophils|Below (baseline) - above (Day 64)
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 64)
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 64)
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 64)
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 64)
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 64)
    0
    0
    0
        Platelets|Below (baseline) - above (Day 64)
    0
    0
    0
        WBC|Below (baseline) - above (Day 64)
    0
    0
    0
        ALT|Within (baseline) - above (Day 64)
    2
    1
    1
        AST|Within (baseline) - above (Day 64)
    1
    0
    1
        Creatinine|Within (baseline) - above (Day 64)
    0
    0
    0
        Urea Nitrogen|Within (baseline) - above (Day 64)
    0
    0
    0
        Basophils|Within (baseline) - above (Day 64)
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 64)
    1
    0
    0
        Hemoglobin|Within (baseline) - above (Day 64)
    1
    0
    0
        Lymphocytes|Within (baseline) - above (Day 64)
    2
    1
    0
        Monocytes|Within (baseline) - above (Day 64)
    0
    1
    0
        Neutrophils|Within (baseline) - above (Day 64)
    1
    1
    0
        Platelets|Within (baseline) - above (Day 64)
    3
    3
    0
        WBC|Within (baseline) - above (Day 64)
    1
    2
    0
        ALT|Above (baseline) - above (Day 64)
    1
    2
    2
        AST|Above (baseline) - above (Day 64)
    3
    0
    3
        Creatinine|Above (baseline) - above (Day 64)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 64)
    0
    0
    0
        Basophils|Above (baseline) - above (Day 64)
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 64)
    3
    0
    0
        Hemoglobin|Above (baseline) - above (Day 64)
    4
    3
    2
        Lymphocytes|Above (baseline) - above (Day 64)
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 64)
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 64)
    1
    1
    0
        Platelets|Above (baseline) - above (Day 64)
    6
    5
    3
        WBC|Above (baseline) - above (Day 64)
    1
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 176

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 176 [65] [66]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 176 (7 days after the third study intervention administration) compared to Baseline (Day 169)
    Notes
    [65] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [66] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    42
    38
    14
    Units: Participants
        ALT|Below (baseline) - below (Day 176)
    0
    0
    0
        AST|Below (baseline) - below (Day 176)
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 176)
    4
    3
    1
        Urea Nitrogen|Below (baseline) - below (Day 176)
    5
    5
    2
        Basophils|Below (baseline) - below (Day 176)
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 176)
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 176)
    2
    0
    0
        Lymphocytes|Below (baseline) - below (Day 176)
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 176)
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 176)
    0
    0
    0
        Platelets|Below (baseline) - below (Day 176)
    1
    0
    0
        WBC|Below (baseline) - below (Day 176)
    0
    0
    0
        ALT|Within (baseline) - below (Day 176)
    0
    0
    0
        AST|Within (baseline) - below (Day 176)
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 176)
    3
    1
    0
        Urea Nitrogen|Within (baseline) - below (Day 176)
    7
    5
    5
        Basophils|Within (baseline) - below (Day 176)
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 176)
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 176)
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 176)
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 176)
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 176)
    0
    0
    0
        Platelets|Within (baseline) - below (Day 176)
    0
    0
    0
        WBC|Within (baseline) - below (Day 176)
    0
    0
    0
        ALT|Above (baseline) - below (Day 176)
    0
    0
    0
        AST|Above (baseline) - below (Day 176)
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 176)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 176)
    0
    0
    0
        Basophils|Above (baseline) - below (Day 176)
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 176)
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 176)
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 176)
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 176)
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 176)
    0
    0
    0
        Platelets|Above (baseline) - below (Day 176)
    0
    0
    0
        WBC|Above (baseline) - below (Day 176)
    0
    0
    0
        ALT|Below (baseline) - within (Day 176)
    0
    0
    0
        AST|Below (baseline) - within (Day 176)
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 176)
    0
    1
    0
        Urea Nitrogen|Below (baseline) - within (Day 176)
    7
    0
    2
        Basophils|Below (baseline) - within (Day 176)
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 176)
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 176)
    0
    0
    0
        Lymphocytes|Below (baseline) - within (Day 176)
    0
    0
    14
        Monocytes|Below (baseline) - within (Day 176)
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 176)
    0
    0
    0
        Platelets|Below (baseline) - within (Day 176)
    0
    1
    0
        WBC|Below (baseline) - within (Day 176)
    0
    0
    0
        ALT|Within (baseline) - within (Day 176)
    37
    34
    14
        AST|Within (baseline) - within (Day 176)
    34
    33
    13
        Creatinine|Within (baseline) - within (Day 176)
    35
    33
    13
        Urea Nitrogen|Within (baseline) - within (Day 176)
    23
    28
    5
        Basophils|Within (baseline) - within (Day 176)
    42
    38
    14
        Eosinophils|Within (baseline) - within (Day 176)
    42
    38
    14
        Hemoglobin|Within (baseline) - within (Day 176)
    25
    28
    7
        Lymphocytes|Within (baseline) - within (Day 176)
    40
    36
    0
        Monocytes|Within (baseline) - within (Day 176)
    39
    37
    14
        Neutrophils|Within (baseline) - within (Day 176)
    40
    35
    14
        Platelets|Within (baseline) - within (Day 176)
    29
    24
    11
        WBC|Within (baseline) - within (Day 176)
    41
    36
    14
        ALT|Above (baseline) - within (Day 176)
    3
    2
    0
        AST|Above (baseline) - within (Day 176)
    3
    3
    0
        Creatinine|Above (baseline) - within (Day 176)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 176)
    0
    0
    0
        Basophils|Above (baseline) - within (Day 176)
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 176)
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 176)
    5
    4
    3
        Lymphocytes|Above (baseline) - within (Day 176)
    1
    0
    0
        Monocytes|Above (baseline) - within (Day 176)
    1
    1
    0
        Neutrophils|Above (baseline) - within (Day 176)
    0
    0
    0
        Platelets|Above (baseline) - within (Day 176)
    1
    0
    0
        WBC|Above (baseline) - within (Day 176)
    0
    0
    0
        ALT|Below (baseline) - above (Day 176)
    0
    0
    0
        AST|Below (baseline) - above (Day 176)
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 176)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 176)
    0
    0
    0
        Basophils|Below (baseline) - above (Day 176)
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 176)
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 176)
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 176)
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 176)
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 176)
    0
    0
    0
        Platelets|Below (baseline) - above (Day 176)
    0
    0
    0
        WBC|Below (baseline) - above (Day 176)
    0
    0
    0
        ALT|Within (baseline) - above (Day 176)
    1
    2
    0
        AST|Within (baseline) - above (Day 176)
    3
    1
    0
        Creatinine|Within (baseline) - above (Day 176)
    0
    0
    0
        Urea Nitrogen|Within (baseline) - above (Day 176)
    0
    0
    0
        Basophils|Within (baseline) - above (Day 176)
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 176)
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 176)
    4
    2
    0
        Lymphocytes|Within (baseline) - above (Day 176)
    0
    1
    0
        Monocytes|Within (baseline) - above (Day 176)
    1
    0
    0
        Neutrophils|Within (baseline) - above (Day 176)
    2
    1
    0
        Platelets|Within (baseline) - above (Day 176)
    6
    4
    1
        WBC|Within (baseline) - above (Day 176)
    1
    0
    0
        ALT|Above (baseline) - above (Day 176)
    1
    0
    0
        AST|Above (baseline) - above (Day 176)
    2
    1
    1
        Creatinine|Above (baseline) - above (Day 176)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 176)
    0
    0
    0
        Basophils|Above (baseline) - above (Day 176)
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 176)
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 176)
    6
    4
    4
        Lymphocytes|Above (baseline) - above (Day 176)
    1
    1
    0
        Monocytes|Above (baseline) - above (Day 176)
    1
    0
    0
        Neutrophils|Above (baseline) - above (Day 176)
    0
    2
    0
        Platelets|Above (baseline) - above (Day 176)
    5
    9
    2
        WBC|Above (baseline) - above (Day 176)
    0
    2
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 29

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 29 [67] [68]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)
    Notes
    [67] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [68] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    45
    15
    Units: Participants
        ALT|Below (baseline) - below (Day 29)
    0
    0
    0
        AST|Below (baseline) - below (Day 29)
    1
    0
    0
        Creatinine|Below (baseline) - below (Day 29)
    3
    2
    1
        Urea Nitrogen|Below (baseline) - below (Day 29)
    4
    3
    3
        Basophils|Below (baseline) - below (Day 29)
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 29)
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 29)
    0
    0
    0
        Lymphocytes|Below (baseline) - below (Day 29)
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 29)
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 29)
    0
    0
    0
        Platelets|Below (baseline) - below (Day 29)
    1
    0
    0
        WBC|elow (baseline) - below (Day 29)
    0
    0
    0
        ALT|Within (baseline) - below (Day 29)
    3
    1
    0
        AST|Within (baseline) - below (Day 29)
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 29)
    1
    0
    0
        Urea Nitrogen|Within (baseline) - below (Day 29)
    8
    6
    3
        Basophils|Within (baseline) - below (Day 29)
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 29)
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 29)
    1
    0
    0
        Lymphocytes|Within (baseline) - below (Day 29)
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 29)
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 29)
    1
    0
    0
        Platelets|Within (baseline) - below (Day 29)
    0
    0
    0
        WBC|Within (baseline) - below (Day 29)
    0
    0
    1
        ALT|Above (baseline) - below (Day 29)
    0
    0
    0
        AST|Above (baseline) - below (Day 29)
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 29)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 29)
    0
    0
    0
        Basophils|Above (baseline) - below (Day 29)
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 29)
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 29)
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 29)
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 29)
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 29)
    0
    0
    0
        Platelets|Above (baseline) - below (Day 29)
    0
    0
    0
        WBC|Above (baseline) - below (Day 29)
    0
    0
    0
        ALT|Below (baseline) - within (Day 29)
    0
    0
    0
        AST|Below (baseline) - within (Day 29)
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 29)
    0
    1
    0
        Urea Nitrogen|Below (baseline) - within (Day 29)
    8
    9
    1
        Basophils|Below (baseline) - within (Day 29)
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 29)
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 29)
    1
    0
    0
        Lymphocytes|Below (baseline) - within (Day 29)
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 29)
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 29)
    0
    0
    0
        Platelets|Below (baseline) - within (Day 29)
    0
    1
    0
        WBC|Below (baseline) - within (Day 29)
    0
    0
    0
        ALT|Within (baseline) - within (Day 29)
    35
    31
    12
        AST|Within (baseline) - within (Day 29)
    39
    41
    11
        Creatinine|Within (baseline) - within (Day 29)
    41
    42
    14
        Urea Nitrogen|Within (baseline) - within (Day 29)
    25
    27
    8
        Basophils|Within (baseline) - within (Day 29)
    45
    44
    15
        Eosinophils|Within (baseline) - within (Day 29)
    45
    45
    15
        Hemoglobin|Within (baseline) - within (Day 29)
    38
    39
    12
        Lymphocytes|Within (baseline) - within (Day 29)
    44
    44
    13
        Monocytes|Within (baseline) - within (Day 29)
    44
    45
    15
        Neutrophils|Within (baseline) - within (Day 29)
    41
    43
    15
        Platelets|Within (baseline) - within (Day 29)
    39
    36
    12
        WBC|Within (baseline) - within (Day 29)
    43
    43
    13
        ALT|Above (baseline) - within (Day 29)
    5
    5
    2
        AST|Above (baseline) - within (Day 29)
    3
    0
    1
        Creatinine|Above (baseline) - within (Day 29)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 29)
    0
    0
    0
        Basophils|Above (baseline) - within (Day 29)
    0
    1
    0
        Eosinophils|Above (baseline) - within (Day 29)
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 29)
    0
    1
    0
        Lymphocytes|Above (baseline) - within (Day 29)
    1
    0
    2
        Monocytes|Above (baseline) - within (Day 29)
    0
    0
    0
        Neutrophils|Above (baseline) - within (Day 29)
    1
    1
    0
        Platelets|Above (baseline) - within (Day 29)
    2
    2
    0
        WBC|Above (baseline) - within (Day 29)
    0
    2
    1
        ALT|Below (baseline) - above (Day 29)
    0
    0
    0
        AST|Below (baseline) - above (Day 29)
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 29)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 29)
    0
    0
    0
        Basophils|Below (baseline) - above (Day 29)
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 29)
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 29)
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 29)
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 29)
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 29)
    0
    0
    0
        Platelets|Below (baseline) - above (Day 29)
    0
    0
    0
        WBC|Below (baseline) - above (Day 29)
    0
    0
    0
        ALT|Within (baseline) - above (Day 29)
    2
    6
    1
        AST|Within (baseline) - above (Day 29)
    1
    2
    1
        Creatinine|Within (baseline) - above (Day 29)
    0
    0
    0
        Urea Nitrogen|Within (baseline) - above (Day 29)
    0
    0
    0
        Basophils|Within (baseline) - above (Day 29)
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 29)
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 29)
    1
    2
    1
        Lymphocytes|Within (baseline) - above (Day 29)
    0
    1
    0
        Monocytes|Within (baseline) - above (Day 29)
    1
    0
    0
        Neutrophils|Within (baseline) - above (Day 29)
    2
    0
    0
        Platelets|Within (baseline) - above (Day 29)
    1
    1
    0
        WBC|Within (baseline) - above (Day 29)
    1
    0
    0
        ALT|Above (baseline) - above (Day 29)
    0
    2
    0
        AST|Above (baseline) - above (Day 29)
    1
    2
    2
        Creatinine|Above (baseline) - above (Day 29)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 29)
    0
    0
    0
        Basophils|Above (baseline) - above (Day 29)
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 29)
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 29)
    4
    3
    2
        Lymphocytes|Above (baseline) - above (Day 29)
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 29)
    0
    0
    0
        Neutrophils|Above (baseline) - above (Day 29)
    0
    1
    0
        Platelets|Above (baseline) - above (Day 29)
    2
    5
    3
        WBC|Above (baseline) - above (Day 29)
    1
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 85

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 85 [69] [70]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)
    Notes
    [69] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [70] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    43
    15
    Units: Participants
        ALT|Below (baseline) - below (Day 85)
    1
    0
    0
        AST|Below (baseline) - below (Day 85)
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 85)
    3
    4
    1
        Urea Nitrogen|Below (baseline) - below (Day 85)
    9
    4
    3
        Basophils|Below (baseline) - below (Day 85)
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 85)
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 85)
    1
    0
    0
        Lymphocytes|Below (baseline) - below (Day 85)
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 85)
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 85)
    0
    0
    0
        Platelets|Below (baseline) - below (Day 85)
    1
    0
    0
        WBC|Below (baseline) - below (Day 85)
    0
    0
    0
        ALT|Within (baseline) - below (Day 85)
    0
    1
    0
        AST|Within (baseline) - below (Day 85)
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 85)
    3
    1
    1
        Urea Nitrogen|Within (baseline) - below (Day 85)
    3
    6
    1
        Basophils|Within (baseline) - below (Day 85)
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 85)
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 85)
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 85)
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 85)
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 85)
    0
    0
    0
        Platelets|Within (baseline) - below (Day 85)
    1
    0
    0
        WBC|Within (baseline) - below (Day 85)
    0
    0
    0
        ALT|Above (baseline) - below (Day 85)
    0
    0
    0
        AST|Above (baseline) - below (Day 85)
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 85)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 85)
    0
    0
    0
        Basophils|Above (baseline) - below (Day 85)
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 85)
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 85)
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 85)
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 85)
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 85)
    0
    0
    0
        Platelets|Above (baseline) - below (Day 85)
    1
    0
    0
        WBC|Above (baseline) - below (Day 85)
    0
    0
    0
        ALT|Below (baseline) - within (Day 85)
    0
    0
    0
        AST|Below (baseline) - within (Day 85)
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 85)
    0
    3
    0
        Urea Nitrogen|Below (baseline) - within (Day 85)
    6
    3
    3
        Basophils|Below (baseline) - within (Day 85)
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 85)
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 85)
    1
    0
    0
        Lymphocytes|Below (baseline) - within (Day 85)
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 85)
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 85)
    0
    0
    0
        Platelets|Below (baseline) - within (Day 85)
    0
    0
    0
        WBC|Below (baseline) - within (Day 85)
    0
    0
    0
        ALT|Within (baseline) - within (Day 85)
    39
    33
    13
        AST|Within (baseline) - within (Day 85)
    40
    36
    12
        Creatinine|Within (baseline) - within (Day 85)
    39
    35
    13
        Urea Nitrogen|Within (baseline) - within (Day 85)
    27
    30
    8
        Basophils|Within (baseline) - within (Day 85)
    43
    43
    15
        Eosinophils|Within (baseline) - within (Day 85)
    41
    43
    15
        Hemoglobin|Within (baseline) - within (Day 85)
    36
    38
    12
        Lymphocytes|Within (baseline) - within (Day 85)
    43
    42
    15
        Monocytes|Within (baseline) - within (Day 85)
    44
    42
    15
        Neutrophils|Within (baseline) - within (Day 85)
    41
    41
    14
        Platelets|Within (baseline) - within (Day 85)
    33
    37
    12
        WBC|Within (baseline) - within (Day 85)
    42
    43
    15
        ALT|Above (baseline) - within (Day 85)
    2
    6
    2
        AST|Above (baseline) - within (Day 85)
    2
    2
    1
        Creatinine|Above (baseline) - within (Day 85)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 85)
    0
    0
    0
        Basophils|Above (baseline) - within (Day 85)
    1
    0
    0
        Eosinophils|Above (baseline) - within (Day 85)
    1
    0
    0
        Hemoglobin|Above (baseline) - within (Day 85)
    1
    2
    0
        Lymphocytes|Above (baseline) - within (Day 85)
    0
    0
    0
        Monocytes|Above (baseline) - within (Day 85)
    1
    0
    0
        Neutrophils|Above (baseline) - within (Day 85)
    3
    1
    1
        Platelets|Above (baseline) - within (Day 85)
    3
    1
    1
        WBC|Above (baseline) - within (Day 85)
    3
    0
    0
        ALT|Below (baseline) - above (Day 85)
    0
    0
    0
        AST|Below (baseline) - above (Day 85)
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 85)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 85)
    0
    0
    0
        Basophils|Below (baseline) - above (Day 85)
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 85)
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 85)
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 85)
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 85)
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 85)
    0
    0
    0
        Platelets|Below (baseline) - above (Day 85)
    0
    0
    0
        WBC|Below (baseline) - above (Day 85)
    0
    0
    0
        ALT|Within (baseline) - above (Day 85)
    2
    3
    0
        AST|Within (baseline) - above (Day 85)
    1
    3
    0
        Creatinine|Within (baseline) - above (Day 85)
    0
    0
    0
        Urea Nitrogen|Within (baseline) - above (Day 85)
    0
    0
    0
        Basophils|Within (baseline) - above (Day 85)
    1
    0
    0
        Eosinophils|Within (baseline) - above (Day 85)
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 85)
    2
    0
    1
        Lymphocytes|Within (baseline) - above (Day 85)
    2
    1
    0
        Monocytes|Within (baseline) - above (Day 85)
    0
    0
    0
        Neutrophils|Within (baseline) - above (Day 85)
    1
    0
    0
        Platelets|Within (baseline) - above (Day 85)
    3
    1
    0
        WBC|Within (baseline) - above (Day 85)
    0
    0
    0
        ALT|Above (baseline) - above (Day 85)
    1
    0
    0
        AST|Above (baseline) - above (Day 85)
    2
    2
    2
        Creatinine|Above (baseline) - above (Day 85)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 85)
    0
    0
    0
        Basophils|Above (baseline) - above (Day 85)
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 85)
    3
    0
    0
        Hemoglobin|Above (baseline) - above (Day 85)
    4
    3
    2
        Lymphocytes|Above (baseline) - above (Day 85)
    0
    0
    0
        Monocytes|Above (baseline) - above (Day 85)
    0
    1
    0
        Neutrophils|Above (baseline) - above (Day 85)
    0
    1
    0
        Platelets|Above (baseline) - above (Day 85)
    3
    4
    2
        WBC|Above (baseline) - above (Day 85)
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 197

    		 Close Top of page
    End point title
    		 Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 197 [71] [72]
    End point description
    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Primary
    End point timeframe
    At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)
    Notes
    [71] - 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 this primary endpoint was descriptive i.e. No statistical hypothesis test was performed.
    [72] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    42
    38
    14
    Units: Participants
        ALT|Below (baseline) - below (Day 197)
    0
    0
    0
        AST|Below (baseline) - below (Day 197)
    0
    0
    0
        Creatinine|Below (baseline) - below (Day 197)
    4
    4
    1
        Urea Nitrogen|Below (baseline) - below (Day 197)
    4
    3
    3
        Basophils|Below (baseline) - below (Day 197)
    0
    0
    0
        Eosinophils|Below (baseline) - below (Day 197)
    0
    0
    0
        Hemoglobin|Below (baseline) - below (Day 197)
    1
    0
    0
        Lymphocytes|Below (baseline) - below (Day 197)
    0
    0
    0
        Monocytes|Below (baseline) - below (Day 197)
    0
    0
    0
        Neutrophils|Below (baseline) - below (Day 197)
    0
    0
    0
        Platelets|Below (baseline) - below (Day 197)
    1
    0
    0
        WBC|Below (baseline) - below (Day 197)
    0
    0
    0
        ALT|Within (baseline) - below (Day 197)
    0
    0
    0
        AST|Within (baseline) - below (Day 197)
    0
    0
    0
        Creatinine|Within (baseline) - below (Day 197)
    2
    1
    0
        Urea Nitrogen|Within (baseline) - below (Day 197)
    9
    5
    1
        Basophils|Within (baseline) - below (Day 197)
    0
    0
    0
        Eosinophils|Within (baseline) - below (Day 197)
    0
    0
    0
        Hemoglobin|Within (baseline) - below (Day 197)
    0
    0
    0
        Lymphocytes|Within (baseline) - below (Day 197)
    0
    0
    0
        Monocytes|Within (baseline) - below (Day 197)
    0
    0
    0
        Neutrophils|Within (baseline) - below (Day 197)
    0
    1
    0
        Platelets|Within (baseline) - below (Day 197)
    0
    0
    0
        WBC|Within (baseline) - below (Day 197)
    0
    0
    0
        ALT|Above (baseline) - below (Day 197)
    0
    0
    0
        AST|Above (baseline) - below (Day 197)
    0
    0
    0
        Creatinine|Above (baseline) - below (Day 197)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - below (Day 197)
    0
    0
    0
        Basophils|Above (baseline) - below (Day 197)
    0
    0
    0
        Eosinophils|Above (baseline) - below (Day 197)
    0
    0
    0
        Hemoglobin|Above (baseline) - below (Day 197)
    0
    0
    0
        Lymphocytes|Above (baseline) - below (Day 197)
    0
    0
    0
        Monocytes|Above (baseline) - below (Day 197)
    0
    0
    0
        Neutrophils|Above (baseline) - below (Day 197)
    0
    0
    0
        Platelets|Above (baseline) - below (Day 197)
    1
    0
    0
        WBC]|Above (baseline) - below (Day 197)
    0
    0
    0
        ALT|Below (baseline) - within (Day 197)
    0
    0
    0
        AST|Below (baseline) - within (Day 197)
    0
    0
    0
        Creatinine|Below (baseline) - within (Day 197)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - within (Day 197)
    8
    2
    1
        Basophils|Below (baseline) - within (Day 197)
    0
    0
    0
        Eosinophils|Below (baseline) - within (Day 197)
    0
    0
    0
        Hemoglobin|Below (baseline) - within (Day 197)
    1
    0
    0
        Lymphocytes|Below (baseline) - within (Day 197)
    0
    0
    0
        Monocytes|Below (baseline) - within (Day 197)
    0
    0
    0
        Neutrophils|Below (baseline) - within (Day 197)
    0
    0
    0
        Platelets|Below (baseline) - within (Day 197)
    0
    1
    0
        WBC|Below (baseline) - within (Day 197)
    0
    0
    0
        ALT|Within (baseline) - within (Day 197)
    38
    30
    13
        AST|Within (baseline) - within (Day 197)
    36
    32
    12
        Creatinine|Within (baseline) - within (Day 197)
    35
    33
    13
        Urea Nitrogen|Within (baseline) - within (Day 197)
    21
    28
    9
        Basophils|Within (baseline) - within (Day 197)
    42
    38
    14
        Eosinophils|Within (baseline) - within (Day 197)
    42
    38
    14
        Hemoglobin|Within (baseline) - within (Day 197)
    28
    29
    6
        Lymphocytes|Within (baseline) - within (Day 197)
    39
    37
    14
        Monocytes|Within (baseline) - within (Day 197)
    39
    37
    14
        Neutrophils|Within (baseline) - within (Day 197)
    42
    33
    14
        Platelets|Within (baseline) - within (Day 197)
    33
    28
    11
        WBC|Within (baseline) - within (Day 197)
    41
    36
    14
        ALT|Above (baseline) - within (Day 197)
    3
    2
    0
        AST|Above (baseline) - within (Day 197)
    2
    2
    0
        Creatinine|Above (baseline) - within (Day 197)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - within (Day 197)
    0
    0
    0
        Basophils|Above (baseline) - within (Day 197)
    0
    0
    0
        Eosinophils|Above (baseline) - within (Day 197)
    0
    0
    0
        Hemoglobin|Above (baseline) - within (Day 197)
    6
    2
    3
        Lymphocytes|Above (baseline) - within (Day 197)
    1
    1
    0
        Monocytes|Above (baseline) - within (Day 197)
    1
    1
    0
        Neutrophils|Above (baseline) - within (Day 197)
    0
    1
    0
        Platelets|Above (baseline) - within (Day 197)
    4
    5
    0
        WBC|Above (baseline) - within (Day 197)
    0
    1
    0
        ALT|Below (baseline) - above (Day 197)
    0
    0
    0
        AST|Below (baseline) - above (Day 197)
    0
    0
    0
        Creatinine|Below (baseline) - above (Day 197)
    0
    0
    0
        Urea Nitrogen|Below (baseline) - above (Day 197)
    0
    0
    0
        Basophils|Below (baseline) - above (Day 197)
    0
    0
    0
        Eosinophils|Below (baseline) - above (Day 197)
    0
    0
    0
        Hemoglobin|Below (baseline) - above (Day 197)
    0
    0
    0
        Lymphocytes|Below (baseline) - above (Day 197)
    0
    0
    0
        Monocytes|Below (baseline) - above (Day 197)
    0
    0
    0
        Neutrophils|Below (baseline) - above (Day 197)
    0
    0
    0
        Platelets|Below (baseline) - above (Day 197)
    0
    0
    0
        WBC|Below (baseline) - above (Day 197)
    0
    0
    0
        ALT|Within (baseline) - above (Day 197)
    0
    6
    1
        AST|Within (baseline) - above (Day 197)
    1
    2
    1
        Creatinine|Within (baseline) - above (Day 197)
    1
    0
    0
        Urea Nitrogen|Within (baseline) - above (Day 197)
    0
    0
    0
        Basophils|Within (baseline) - above (Day 197)
    0
    0
    0
        Eosinophils|Within (baseline) - above (Day 197)
    0
    0
    0
        Hemoglobin|Within (baseline) - above (Day 197)
    1
    1
    1
        Lymphocytes|Within (baseline) - above (Day 197)
    1
    0
    0
        Monocytes|Within (baseline) - above (Day 197)
    1
    0
    0
        Neutrophils|Within (baseline) - above (Day 197)
    0
    2
    0
        Platelets|Within (baseline) - above (Day 197)
    2
    0
    1
        WBC|Within (baseline) - above (Day 197)
    1
    0
    0
        ALT|Above (baseline) - above (Day 197)
    1
    0
    0
        AST|Above (baseline) - above (Day 197)
    3
    2
    1
        Creatinine|Above (baseline) - above (Day 197)
    0
    0
    0
        Urea Nitrogen|Above (baseline) - above (Day 197)
    0
    0
    0
        Basophils|Above (baseline) - above (Day 197)
    0
    0
    0
        Eosinophils|Above (baseline) - above (Day 197)
    0
    0
    0
        Hemoglobin|Above (baseline) - above (Day 197)
    5
    6
    4
        Lymphocytes|Above (baseline) - above (Day 197)
    1
    0
    0
        Monocytes|Above (baseline) - above (Day 197)
    1
    0
    0
        Neutrophils|Above (baseline) - above (Day 197)
    0
    1
    0
        Platelets|Above (baseline) - above (Day 197)
    1
    4
    2
        WBC|Above (baseline) - above (Day 197)
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Stage 1 and Stage 2: Number of participants with any SAEs

    		 Close Top of page
    End point title
    		 Stage 1 and Stage 2: Number of participants with any SAEs
    End point description
    An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    4
    4
    16
    16
    10
    45
    45
    15
    Units: Participants
    0
    0
    0
    0
    0
    0
    1
    1
    No statistical analyses for this end point

    Secondary: Stage 1 and Stage 2: Number of participants with any AEs/SAEs leading to withdrawal from the study

    		 Close Top of page
    End point title
    		 Stage 1 and Stage 2: Number of participants with any AEs/SAEs leading to withdrawal from the study
    End point description
    Any AEs including SAEs that lead to withdrawal from the study are considered under this outcome measure. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for him/her since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade. The analysis was performed on the exposed set. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    4
    4
    16
    16
    10
    45
    45
    15
    Units: Participants
    0
    0
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Stage 1: Geometric mean concentrations (GMCs) of anti-serotype specific immunoglobulin G (IgG) in participants and between group ratios - Anti-Vi antigen (Ag) total IgG

    		 Close Top of page
    End point title
    		 Stage 1: Geometric mean concentrations (GMCs) of anti-serotype specific immunoglobulin G (IgG) in participants and between group ratios - Anti-Vi antigen (Ag) total IgG [73]
    End point description
    Anti-Vi antigen (Ag) total IgG GMCs were assessed. Blood samples were collected at specified timepoint for each component as measured by Enzyme-Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) for antibody concentrations was >=2.2 microgram per milliliter (µg/mL). In case the measured antibody concentration fell below 2.2 µg/mL, a value of half the LLOQ value was imputed. The analysis was performed on the Per Protocol Set (PPS), that included all eligible participants who received all doses as per protocol, had immunogenicity results post-dose, complied with dosing/blood draw intervals, without intercurrent conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)
    Notes
    [73] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: microgram per milliliter (µg/mL)
    geometric mean (confidence interval 95%)
        Anti-Vi Ag total IgG, Day 1
    1.10 (1.10 to 1.10)
    1.10 (1.10 to 1.10)
    1.10 (1.10 to 1.10)
    1.10 (1.10 to 1.10)
    1.10 (1.10 to 1.10)
        Anti-Vi Ag total IgG, Day 29
    30.29 (13.50 to 67.95)
    68.87 (1.73 to 2741.00)
    43.55 (18.51 to 102.49)
    66.48 (37.31 to 118.46)
    1.10 (1.10 to 1.10)
        Anti-Vi Ag total IgG, Day 57
    23.28 (16.49 to 32.89)
    53.95 (2.37 to 1226.99)
    25.99 (9.86 to 68.50)
    51.01 (27.55 to 94.46)
    1.10 (1.10 to 1.10)
        Anti-Vi Ag total IgG, Day 85
    30.52 (14.75 to 63.13)
    51.71 (3.42 to 781.48)
    34.02 (16.67 to 69.44)
    51.65 (31.18 to 85.55)
    1.10 (1.10 to 1.10)
        Anti-Vi Ag total IgG, Day 169
    13.61 (4.28 to 43.23)
    14.11 (0.22 to 10265.73)
    15.76 (8.14 to 30.48)
    20.69 (12.68 to 33.76)
    1.10 (1.10 to 1.10)
        Anti-Vi Ag total IgG, Day 197
    20.19 (1.48 to 275.08)
    17.43 (0.01 to 26224.47)
    31.84 (16.24 to 62.43)
    35.24 (23.65 to 52.49)
    1.10 (1.10 to 1.10)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 29
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [74]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 3.43
    Notes
    [74] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 29
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [75]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 1.7
    Notes
    [75] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 197
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [76]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.44
         upper limit
    		 1.84
    Notes
    [76] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 85
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [77]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3
         upper limit
    		 1.43
    Notes
    [77] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 169
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [78]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.18
         upper limit
    		 5.12
    Notes
    [78] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 169
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [79]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.36
         upper limit
    		 1.6
    Notes
    [79] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 197
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [80]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 5.79
    Notes
    [80] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 57
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [81]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 1.37
    Notes
    [81] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 57
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [82]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.06
         upper limit
    		 2.94
    Notes
    [82] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-Vi Ag IgG, Day 85
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [83]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.13
         upper limit
    		 2.65
    Notes
    [83] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.

    Secondary: Stage 1: GMCs of anti-serotype specific IgG in participants and between group ratios - Anti-S. Typhimurium OAg total IgG and Anti S. Enteritidis OAg total IgG

    		 Close Top of page
    End point title
    		 Stage 1: GMCs of anti-serotype specific IgG in participants and between group ratios - Anti-S. Typhimurium OAg total IgG and Anti S. Enteritidis OAg total IgG [84]
    End point description
    Anti-S. Typhimurium OAg total IgG, Anti S. Enteritidis OAg total IgG GMCs were assessed. Blood samples were collected at specified timepoint for each component as measured by Enzyme-Linked Immunosorbent Assay (ELISA). The analysis was performed on the Per Protocol Set (PPS), that included all eligible participants who received all doses as per protocol, had immunogenicity results post-dose, complied with dosing/blood draw intervals, without intercurrent conditions that may interfere with immunogenicity and without prohibited concomitant medication/vaccination. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)
    Notes
    [84] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    4
    16
    16
    10
    Units: ELISA units per milliliter (EU/mL)
    geometric mean (confidence interval 95%)
        Anti-S.Typhimurium OAg IgG, Day 1
    20.25 (3.23 to 126.95)
    49.45 (0.68 to 3599.82)
    94.10 (34.63 to 255.69)
    124.02 (54.83 to 280.53)
    52.23 (19.31 to 141.31)
        Anti-S.Typhimurium OAg IgG, Day 29
    494.50 (80.16 to 3050.49)
    169.25 (4.35 to 6586.95)
    1426.07 (777.69 to 2615.85)
    1505.55 (815.65 to 2778.99)
    52.86 (19.93 to 140.20)
        Anti-S.Typhimurium OAg IgG, Day 57
    423.33 (81.46 to 2200.08)
    139.78 (5.42 to 3604.75)
    1075.57 (466.12 to 2481.85)
    1203.79 (589.73 to 2457.26)
    58.38 (16.45 to 207.16)
        Anti-S.Typhimurium OAg IgG, Day 85
    410.29 (87.67 to 1920.18)
    243.42 (3.18 to 18606.83)
    1129.27 (497.20 to 2564.86)
    1478.01 (804.57 to 2715.11)
    68.07 (17.22 to 269.09)
        Anti-S.Typhimurium OAg IgG, Day 169
    272.19 (43.10 to 1718.88)
    109.20 (0.00 to 1040000000000)
    703.74 (296.98 to 1667.63)
    951.71 (498.59 to 1816.63)
    75.80 (21.92 to 262.14)
        Anti-S.Typhimurium OAg IgG, Day 197
    249.07 (21.83 to 2842.34)
    163.07 (0.00 to 1190000000000)
    1005.05 (445.54 to 2267.20)
    1176.88 (719.47 to 1925.10)
    73.43 (21.98 to 245.25)
        Anti-S.Enteritidis OAg IgG, Day 1
    67.85 (6.04 to 761.69)
    42.77 (0.32 to 5784.66)
    125.64 (47.39 to 333.09)
    115.74 (46.32 to 289.22)
    57.08 (21.97 to 148.25)
        Anti-S.Enteritidis OAg IgG, Day 29
    920.64 (104.11 to 8141.15)
    169.46 (0.32 to 90734.61)
    1648.46 (1023.81 to 2654.22)
    1387.16 (587.94 to 3272.77)
    56.62 (21.49 to 149.13)
        Anti-S.Enteritidis OAg IgG, Day 57
    832.83 (110.24 to 6291.99)
    141.59 (0.42 to 47560.41)
    1454.26 (801.81 to 2637.64)
    1076.32 (400.41 to 2893.21)
    65.49 (18.13 to 236.58)
        Anti-S.Enteritidis OAg IgG, Day 85
    882.68 (132.51 to 5879.62)
    209.03 (0.88 to 49901.51)
    1436.56 (779.81 to 2646.42)
    1267.65 (511.67 to 3140.56)
    79.79 (18.55 to 343.09)
        Anti-S.Enteritidis OAg IgG, Day 169
    557.81 (78.28 to 3975.01)
    42.14 (0.01 to 162000)
    903.37 (487.13 to 1675.30)
    729.86 (255.41 to 2085.64)
    75.96 (20.72 to 278.48)
        Anti-S.Enteritidis OAg IgG, Day 197
    451.36 (22.54 to 9036.65)
    81.17 (0.87 to 7578.12)
    1168.56 (642.31 to 2125.99)
    855.62 (356.65 to 2052.67)
    73.74 (20.17 to 269.56)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 29
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [85]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    2.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 17.8
    Notes
    [85] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 29
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [86]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 2.19
    Notes
    [86] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 57
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [87]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    3.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 21.45
    Notes
    [87] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 57
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [88]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 2.45
    Notes
    [88] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 85
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [89]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 10.96
    Notes
    [89] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 85
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [90]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 2
    Notes
    [90] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 169
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [91]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    2.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 26.3
    Notes
    [91] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 169
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [92]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 2.11
    Notes
    [92] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 197
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [93]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 12.41
    Notes
    [93] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 197
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [94]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 2.15
    Notes
    [94] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 85
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [95]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    4.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 37.19
    Notes
    [95] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 57
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [96]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 4.45
    Notes
    [96] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 57
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [97]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    5.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 59.45
    Notes
    [97] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 29
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [98]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.43
         upper limit
    		 3.26
    Notes
    [98] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 29
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [99]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    5.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 48.17
    Notes
    [99] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 169
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [100]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    13.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 172.55
    Notes
    [100] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 85
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [101]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 3.48
    Notes
    [101] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 169
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [102]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 3.88
    Notes
    [102] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 197
    Comparison groups
    Stage 1: iNTS-TCV low dose group v Stage 1: iNTS-GMMA + TCV low dose group
    Number of subjects included in analysis
    8
    Analysis specification
    Pre-specified
    Analysis type
    		 other [103]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    5.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 58.61
    Notes
    [103] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 197
    Comparison groups
    Stage 1: iNTS-TCV full dose group v Stage 1: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other [104]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 3.86
    Notes
    [104] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.

    Secondary: Stage 1: Geometric mean ratios (GMRs) for anti-serotype specific immunoglobulin G (IgG) concentrations

    		 Close Top of page
    End point title
    		 Stage 1: Geometric mean ratios (GMRs) for anti-serotype specific immunoglobulin G (IgG) concentrations [105]
    End point description
    Anti-Vi antigen (Ag) total IgG, Anti-S. Typhimurium OAg total IgG, Anti‑S. Enteritidis OAg total IgG within-participant GMRs were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)
    Notes
    [105] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    16
    16
    10
    Units: Ratio
    geometric mean (confidence interval 95%)
        Anti-Vi Ag total IgG, Day 29
    27.53 (12.27 to 61.77)
    62.61 (1.57 to 2491.81)
    39.60 (16.83 to 93.18)
    60.44 (33.92 to 107.69)
    1.00 (1.00 to 1.00)
        Anti-Vi Ag total IgG, Day 85
    1.31 (0.80 to 2.14)
    0.96 (0.47 to 1.96)
    1.31 (0.87 to 1.97)
    1.01 (0.78 to 1.31)
    1.00 (1.00 to 1.00)
        Anti-Vi Ag total IgG, Day 197
    1.96 (0.49 to 7.78)
    1.24 (0.60 to 2.55)
    1.99 (1.38 to 2.89)
    1.70 (1.38 to 2.10)
    1.00 (1.00 to 1.00)
        Anti-S.Typhimurium OAg IgG. Day 29
    24.42 (11.30 to 52.75)
    3.42 (0.48 to 24.20)
    15.15 (5.57 to 41.26)
    12.14 (6.83 to 21.58)
    1.01 (0.94 to 1.09)
        Anti-S.Typhimurium OAg IgG. Day 85
    0.97 (0.63 to 1.50)
    1.74 (0.44 to 6.87)
    1.05 (0.86 to 1.28)
    1.23 (0.89 to 1.69)
    1.17 (0.97 to 1.40)
        Anti-S.Typhimurium OAg IgG. Day 197
    1.47 (0.80 to 2.71)
    1.49 (1.14 to 1.95)
    1.20 (1.01 to 1.44)
    1.24 (0.93 to 1.65)
    0.97 (0.90 to 1.04)
        Anti-S.Enteritidis OAg IgG Day 29
    13.57 (3.76 to 48.93)
    3.96 (0.67 to 23.52)
    13.12 (5.41 to 31.80)
    11.98 (6.57 to 21.86)
    0.99 (0.93 to 1.06)
        Anti-S.Enteritidis OAg IgG Day 85
    1.06 (0.90 to 1.24)
    1.48 (0.59 to 3.67)
    0.99 (0.86 to 1.14)
    1.18 (0.82 to 1.69)
    1.22 (0.97 to 1.53)
        Anti-S.Enteritidis OAg IgG Day 197
    1.29 (0.68 to 2.45)
    1.93 (0.05 to 79.54)
    1.15 (1.03 to 1.28)
    1.17 (0.92 to 1.49)
    0.97 (0.95 to 0.99)
    No statistical analyses for this end point

    Secondary: Stage 1: Number of participants achieving at least a 4 fold rise in anti serotype specific immunoglobulin G (IgG) antibody concentration for each antigen (Ag)

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants achieving at least a 4 fold rise in anti serotype specific immunoglobulin G (IgG) antibody concentration for each antigen (Ag) [106]
    End point description
    Anti-Vi Ag total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG antibody concentrations were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration)
    Notes
    [106] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    16
    16
    10
    Units: Participants
        Anti-Vi Ag IgG, Day 29
    4
    3
    13
    16
    0
        Anti-Vi Ag IgG, Day 85
    4
    3
    10
    14
    0
        Anti-Vi Ag IgG, Day 197
    2
    2
    10
    14
    0
        Anti-S.Typhimurium OAg IgG, Day 29
    4
    1
    13
    15
    0
        Anti-S.Typhimurium OAg IgG, Day 85
    4
    2
    8
    14
    1
        Anti-S.Typhimurium OAg IgG, Day 197
    3
    1
    6
    10
    1
        Anti-S.Enteritidis OAg IgG, Day 29
    4
    1
    11
    12
    0
        Anti-S.Enteritidis OAg IgG, Day 85
    4
    2
    7
    11
    1
        Anti-S.Enteritidis OAg IgG, Day 197
    3
    1
    4
    10
    1
    No statistical analyses for this end point

    Secondary: Stage 1: Number of participants with Anti-Vi Ag IgG antibody concentrations greater than or equal to (>=) 4.3 micrograms per milliliter (µg/mL)

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants with Anti-Vi Ag IgG antibody concentrations greater than or equal to (>=) 4.3 micrograms per milliliter (µg/mL) [107]
    End point description
    Blood samples were collected at specified timepoint for each component as measured by ELISA. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)
    Notes
    [107] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 1: Placebo group
    Number of subjects analysed
    4
    3
    16
    16
    10
    Units: Participants
        Day 1 (pre-Dose 1)
    0
    0
    0
    0
    0
        Day 29
    4
    3
    14
    16
    0
        Day 57 (pre-Dose 2)
    4
    3
    9
    14
    0
        Day 85
    4
    3
    12
    14
    0
        Day 169 (pre-Dose 3)
    4
    2
    11
    14
    0
        Day 197
    3
    2
    11
    14
    0
    No statistical analyses for this end point

    Secondary: Stage 2: GMCs of anti-serotype specific IgG in participants and between group ratios - Anti-Vi Ag total IgG

    		 Close Top of page
    End point title
    		 Stage 2: GMCs of anti-serotype specific IgG in participants and between group ratios - Anti-Vi Ag total IgG [108]
    End point description
    Anti-Vi Ag total IgG GMCs and between group ratios were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)
    Notes
    [108] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    44
    15
    Units: µg/mL
    geometric mean (confidence interval 95%)
        Anti-Vi Ag total IgG, Day 1
    1.43 (1.20 to 1.70)
    1.38 (1.13 to 1.69)
    1.56 (1.11 to 2.19)
        Anti-Vi Ag total IgG, Day 29
    148.98 (103.31 to 214.83)
    161.68 (107.38 to 243.46)
    1.55 (1.04 to 2.33)
        Anti-Vi Ag total IgG, Day 57
    96.93 (67.00 to 140.23)
    104.38 (69.77 to 156.16)
    1.60 (1.01 to 2.53)
        Anti-Vi Ag total IgG, Day 85
    96.94 (72.03 to 130.48)
    101.92 (72.02 to 144.24)
    1.65 (1.08 to 2.52)
        Anti-Vi Ag total IgG, Day 169
    41.83 (29.43 to 59.46)
    53.65 (34.97 to 82.32)
    1.88 (1.18 to 2.99)
        Anti-Vi Ag total IgG, Day 197
    65.43 (51.01 to 83.92)
    69.82 (50.09 to 97.30)
    18.60 (8.28 to 41.76)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-S.Typhi Vi Ag IgG Day 29
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [109]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.58
    Notes
    [109] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-S.Typhi Vi Ag IgG Day 57
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [110]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.59
    Notes
    [110] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-S.Typhi Vi Ag IgG Day 197
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [111]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.94
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 1.4
    Notes
    [111] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-S.Typhi Vi Ag IgG Day 169
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [112]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.34
    Notes
    [112] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Antigen Anti-S.Typhi Vi Ag IgG Day 85
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [113]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.49
    Notes
    [113] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.

    Secondary: Stage 2: GMCs of anti-serotype specific IgG in participants and between group ratios - Anti-S. Typhimurium OAg total IgG and Anti‑S. Enteritidis OAg total IgG

    		 Close Top of page
    End point title
    		 Stage 2: GMCs of anti-serotype specific IgG in participants and between group ratios - Anti-S. Typhimurium OAg total IgG and Anti‑S. Enteritidis OAg total IgG [114]
    End point description
    Anti-S. Typhimurium OAg total IgG and Anti S. Enteritidis OAg total IgG GMCs and between group ratios were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)
    Notes
    [114] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    44
    15
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-S.Typhimurium OAg IgG, Day 1
    246.02 (167.63 to 361.07)
    490.94 (378.78 to 636.31)
    392.99 (273.90 to 563.87)
        Anti-S.Typhimurium OAg IgG, Day 29
    1591.68 (1117.07 to 2267.94)
    2585.81 (2024.74 to 3302.35)
    446.22 (290.49 to 685.45)
        Anti-S.Typhimurium OAg IgG, Day 57
    1159.50 (806.72 to 1666.56)
    1794.69 (1419.63 to 2268.85)
    483.46 (329.52 to 709.32)
        Anti-S.Typhimurium OAg IgG, Day 85
    1102.67 (771.64 to 1575.70)
    1765.79 (1395.81 to 2233.85)
    545.05 (355.58 to 835.46)
        Anti-S.Typhimurium OAg IgG, Day 169
    870.80 (552.07 to 1373.57)
    1248.95 (979.10 to 1593.18)
    565.73 (349.09 to 916.82)
        Anti-S.Typhimurium OAg IgG, Day 197
    992.82 (645.92 to 1526.03)
    1748.80 (1359.79 to 2249.09)
    542.87 (340.01 to 866.75)
        Anti-S.Enteritidis OAg IgG, Day 1
    363.08 (228.49 to 576.96)
    376.17 (270.58 to 522.95)
    394.19 (193.54 to 802.88)
        Anti-S.Enteritidis OAg IgG, Day 29
    1884.94 (1272.38 to 2792.41)
    2295.38 (1642.33 to 3208.10)
    457.08 (209.54 to 997.03)
        Anti-S.Enteritidis OAg IgG, Day 57
    1527.50 (1030.99 to 2263.13)
    1581.75 (1153.18 to 2169.60)
    470.88 (214.12 to 1035.51)
        Anti-S.Enteritidis OAg IgG, Day 85
    1604.28 (1109.24 to 2320.23)
    1555.91 (1134.43 to 2133.97)
    456.04 (215.01 to 967.26)
        Anti-S.Enteritidis OAg IgG, Day 169
    946.93 (646.79 to 1386.34)
    1015.74 (727.61 to 1417.95)
    408.69 (190.40 to 877.23)
        Anti-S.Enteritidis OAg IgG, Day 197
    1093.84 (757.63 to 1579.27)
    1327.68 (972.03 to 1813.45)
    423.08 (213.16 to 839.75)
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 29
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [115]
    Method
    		 Mixed models analysis
    Parameter type
    		 Adjusted GMR
    Point estimate
    0.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.69
         upper limit
    		 1.32
    Notes
    [115] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 85
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [116]
    Method
    		 Mixed models analysis
    Parameter type
    		 Adjusted GMR
    Point estimate
    1.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.41
    Notes
    [116] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 169
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [117]
    Method
    		 Mixed models analysis
    Parameter type
    		 Adjusted GMR
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.81
         upper limit
    		 1.77
    Notes
    [117] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 57
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [118]
    Method
    		 Mixed models analysis
    Parameter type
    		 Adjusted GMR
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1.37
    Notes
    [118] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Typhimurium OAg IgG Day 197
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [119]
    Method
    		 Mixed models analysis
    Parameter type
    		 Adjusted GMR
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 1.44
    Notes
    [119] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 29
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [120]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 1.37
    Notes
    [120] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 57
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [121]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 1.59
    Notes
    [121] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 85
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [122]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    1.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.67
    Notes
    [122] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 169
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [123]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 1.54
    Notes
    [123] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.
    Statistical analysis title
    		 Between-group analysis
    Statistical analysis description
    Anti-S.Enteritidis OAg IgG Day 197
    Comparison groups
    Stage 2: iNTS-TCV full dose group v Stage 2: iNTS-GMMA + TCV full dose group
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 other [124]
    Method
    		 ANOVA
    Parameter type
    		 Unadjusted GMR
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.33
    Notes
    [124] - The statistical analyses performed for the study objectives were descriptive. No success criteria were defined for the statistical analyses conducted in this study.

    Secondary: Stage 2: GMRs for anti-serotype specific immunoglobulin G (IgG) concentrations

    		 Close Top of page
    End point title
    		 Stage 2: GMRs for anti-serotype specific immunoglobulin G (IgG) concentrations [125]
    End point description
    Anti-Vi antigen (Ag) total IgG, Anti-S. Typhimurium OAg total IgG, Anti‑S. Enteritidis OAg total IgG within-participant GMRs were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)
    Notes
    [125] - 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: The endpoint is reporting data for only Stage 1 of the baseline period. Stage 2 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    44
    15
    Units: Ratio
    geometric mean (confidence interval 95%)
        Anti-Vi Ag total IgG, Day 29
    104.51 (77.39 to 141.12)
    116.84 (79.82 to 171.01)
    1.00 (0.74 to 1.34)
        Anti-Vi Ag total IgG, Day 85
    1.05 (0.92 to 1.20)
    0.91 (0.83 to 1.00)
    1.03 (0.92 to 1.16)
        Anti-Vi Ag total IgG, Day 197
    1.56 (1.30 to 1.88)
    1.37 (1.10 to 1.69)
    9.89 (5.14 to 19.04)
        Anti-S.Typhimurium OAg IgG. Day 29
    6.47 (4.97 to 8.42)
    5.27 (4.12 to 6.73)
    1.14 (0.83 to 1.55)
        Anti-S.Typhimurium OAg IgG. Day 85
    1.00 (0.92 to 1.10)
    0.97 (0.89 to 1.06)
    1.13 (0.89 to 1.42)
        Anti-S.Typhimurium OAg IgG. Day 197
    1.14 (1.04 to 1.25)
    1.41 (1.18 to 1.70)
    0.96 (0.81 to 1.14)
        Anti-S.Enteritidis OAg IgG Day 29
    5.19 (3.44 to 7.83)
    6.10 (4.47 to 8.33)
    1.16 (0.82 to 1.65)
        Anti-S.Enteritidis OAg IgG Day 85
    1.04 (0.94 to 1.15)
    0.99 (0.90 to 1.10)
    0.97 (0.83 to 1.13)
        Anti-S.Enteritidis OAg IgG Day 197
    1.16 (1.00 to 1.34)
    1.34 (1.11 to 1.62)
    1.04 (0.86 to 1.25)
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants achieving at least a 4 fold rise in anti serotype specific immunoglobulin G (IgG) antibody concentration for each antigen (Ag)

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants achieving at least a 4 fold rise in anti serotype specific immunoglobulin G (IgG) antibody concentration for each antigen (Ag) [126]
    End point description
    Anti-Vi Ag total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG antibody concentrations were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
    Notes
    [126] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    44
    15
    Units: Participants
        Anti-Vi Ag IgG, Day 29
    44
    43
    0
        Anti-Vi Ag IgG, Day 85
    44
    42
    1
        Anti-Vi Ag IgG, Day 197
    41
    37
    9
        Anti-S.Typhimurium OAg IgG, Day 29
    33
    27
    1
        Anti-S.Typhimurium OAg IgG, Day 85
    22
    16
    1
        Anti-S.Typhimurium OAg IgG, 197
    23
    16
    1
        Anti-S.Enteritidis OAg IgG, 29
    23
    27
    1
        Anti-S.Enteritidis OAg IgG, Day 85
    21
    18
    2
        Anti-S.Enteritidis OAg IgG, Day 197
    17
    16
    0
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants with Anti-Vi Ag IgG antibody concentrations >= 4.3 µg/mL

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants with Anti-Vi Ag IgG antibody concentrations >= 4.3 µg/mL [127]
    End point description
    Blood samples were collected at specified timepoint for each component as measured by ELISA. The analysis was performed on the PPS. Only participants with data available at the mentioned timepoints were included in this analysis.
    End point type
    Secondary
    End point timeframe
    At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)
    Notes
    [127] - 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: The endpoint is reporting data for only Stage 2 of the baseline period. Stage 1 data is presented separately.
    End point values
    		 Stage 2: iNTS-TCV full dose group Stage 2: iNTS-GMMA + TCV full dose group Stage 2: Control group
    Number of subjects analysed
    45
    44
    15
    Units: Participants
        Day 1
    4
    3
    3
        Day 29
    45
    44
    3
        Day 57
    45
    44
    3
        Day 85
    44
    43
    3
        Day 169
    41
    37
    3
        Day 197
    41
    37
    12
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    SAEs: From Day 1 to Day 337 (end of study), Solicited AEs: From Day 1 to Day 7, Day 57 to Day 63 and Day 169 to Day 175, and Unsolicited AEs: From Day 1 to Day 28, Day 57 to Day 84 and Day 169 to Day 196.
    Adverse event reporting additional description
    SAEs, solicited AEs and unsolicited AEs were reported for the Exposed set.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v27.1
    Reporting groups
    Reporting group title
    Stage 1: iNTS-TCV low dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-GMMA + TCV low dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-Generalized modules for membrane antigens (GMMA) low dose vaccine and 3 doses of TCV low dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-TCV full dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: iNTS-GMMA + TCV full dose group
    Reporting group description
    		 European participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: iNTS-TCV full dose group
    Reporting group description
    		 African participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 1: Placebo group
    Reporting group description
    		 European participants were randomized to receive 3 doses of Placebo and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Reporting group title
    Stage 2: Control group
    Reporting group description
    		 African participants were randomized to receive MENVEO as comparator and 1 dose of saline on Day 1, BOOSTRIX as comparator and 1 dose of saline on Day 57 and TYPHIM VI as comparator and 1 dose of saline on Day 169.

    Reporting group title
    Stage 2: iNTS-GMMA + TCV full dose group
    Reporting group description
    		 African participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

    Serious adverse events
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 2: iNTS-TCV full dose group Stage 1: Placebo group Stage 2: Control group Stage 2: iNTS-GMMA + TCV full dose group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    2 / 45 (4.44%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Malaria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    0 / 45 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Stage 1: iNTS-TCV low dose group Stage 1: iNTS-GMMA + TCV low dose group Stage 1: iNTS-TCV full dose group Stage 1: iNTS-GMMA + TCV full dose group Stage 2: iNTS-TCV full dose group Stage 1: Placebo group Stage 2: Control group Stage 2: iNTS-GMMA + TCV full dose group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    16 / 16 (100.00%)
    16 / 16 (100.00%)
    43 / 45 (95.56%)
    9 / 10 (90.00%)
    15 / 15 (100.00%)
    45 / 45 (100.00%)
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    General disorders and administration site conditions
    Administration site erythema
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    8 / 16 (50.00%)
    7 / 16 (43.75%)
    6 / 45 (13.33%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    10 / 45 (22.22%)
         occurrences all number
    1
    0
    13
    12
    7
    0
    1
    19
    Administration site pain
         subjects affected / exposed
    4 / 4 (100.00%)
    4 / 4 (100.00%)
    16 / 16 (100.00%)
    16 / 16 (100.00%)
    40 / 45 (88.89%)
    8 / 10 (80.00%)
    13 / 15 (86.67%)
    45 / 45 (100.00%)
         occurrences all number
    15
    13
    44
    54
    145
    19
    39
    180
    Administration site pruritus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Administration site swelling
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 4 (25.00%)
    6 / 16 (37.50%)
    3 / 16 (18.75%)
    13 / 45 (28.89%)
    0 / 10 (0.00%)
    2 / 15 (13.33%)
    15 / 45 (33.33%)
         occurrences all number
    1
    1
    8
    5
    23
    0
    4
    40
    Administration site warmth
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Chills
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    2 / 16 (12.50%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    0
    2
    Fatigue
         subjects affected / exposed
    2 / 4 (50.00%)
    4 / 4 (100.00%)
    10 / 16 (62.50%)
    12 / 16 (75.00%)
    31 / 45 (68.89%)
    3 / 10 (30.00%)
    6 / 15 (40.00%)
    30 / 45 (66.67%)
         occurrences all number
    4
    5
    18
    24
    59
    3
    10
    62
    Feeling hot
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    3 / 16 (18.75%)
    0 / 45 (0.00%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    3
    0
    1
    0
    0
    Injection site hyperaesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Injection site pruritus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    3 / 16 (18.75%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    4
    0
    0
    0
    2
    Injection site induration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    Injection site rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Injection site warmth
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 16 (12.50%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    2 / 16 (12.50%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    2
    3
    0
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 4 (0.00%)
    2 / 4 (50.00%)
    3 / 16 (18.75%)
    2 / 16 (12.50%)
    13 / 45 (28.89%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    15 / 45 (33.33%)
         occurrences all number
    0
    2
    4
    2
    17
    1
    0
    20
    Thirst
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Vessel puncture site haematoma
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Vessel puncture site pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    2
    Hypothermia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vaccination site urticaria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    5 / 45 (11.11%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    6
    Reproductive system and breast disorders
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Penile pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    0
    0
    1
    3
    0
    0
    5
    Nasal congestion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    2
    Dysphonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    2 / 10 (20.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    2
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 16 (18.75%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    3
    0
    2
    0
    0
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 16 (12.50%)
    2 / 16 (12.50%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    2
    2
    1
    0
    0
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Platelet count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Neutrophil count increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 16 (12.50%)
    1 / 16 (6.25%)
    1 / 45 (2.22%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    2
    1
    1
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Heart rate decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Blood creatinine decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    Limb injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    1
    Cataract traumatic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Animal bite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Radius fracture
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Soft tissue injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    3
    Wound
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Thermal burn
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 4 (75.00%)
    3 / 4 (75.00%)
    8 / 16 (50.00%)
    11 / 16 (68.75%)
    38 / 45 (84.44%)
    4 / 10 (40.00%)
    8 / 15 (53.33%)
    35 / 45 (77.78%)
         occurrences all number
    4
    4
    15
    19
    70
    4
    12
    77
    Paraesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    0
    3
    Dizziness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    6 / 45 (13.33%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    7 / 45 (15.56%)
         occurrences all number
    0
    0
    0
    0
    7
    0
    1
    7
    Loss of consciousness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Syncope
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Neutrophilia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Monocytosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Lymphopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Leukocytosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Ear pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Eye disorders
    Chalazion
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Photophobia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Ocular hyperaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Eye pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 16 (6.25%)
    2 / 16 (12.50%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    2
    1
    2
    1
    0
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    4
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    2 / 45 (4.44%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    1
    2
    1
    0
    2
    Abdominal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Toothache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Hypoaesthesia oral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Ecchymosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Pigmentation disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Pruritus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    1 / 16 (6.25%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    2
    Rash erythematous
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Rash
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    2
    Erythema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    6
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    Urethral discharge
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    3 / 16 (18.75%)
    4 / 16 (25.00%)
    21 / 45 (46.67%)
    0 / 10 (0.00%)
    8 / 15 (53.33%)
    20 / 45 (44.44%)
         occurrences all number
    1
    2
    5
    7
    36
    0
    11
    37
    Pain in jaw
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    0
    1
    Myalgia
         subjects affected / exposed
    4 / 4 (100.00%)
    3 / 4 (75.00%)
    9 / 16 (56.25%)
    11 / 16 (68.75%)
    29 / 45 (64.44%)
    1 / 10 (10.00%)
    6 / 15 (40.00%)
    31 / 45 (68.89%)
         occurrences all number
    7
    3
    15
    20
    58
    1
    12
    60
    Musculoskeletal stiffness
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    2 / 16 (12.50%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    2
    1
    2
    1
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    1 / 10 (10.00%)
    1 / 15 (6.67%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    1
    1
    0
    Sacral pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    1
    Musculoskeletal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    2 / 45 (4.44%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    1
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Muscle swelling
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    4
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    1 / 10 (10.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    3 / 45 (6.67%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    4 / 45 (8.89%)
         occurrences all number
    0
    0
    1
    0
    3
    0
    1
    5
    Epididymitis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 16 (12.50%)
    4 / 16 (25.00%)
    0 / 45 (0.00%)
    2 / 10 (20.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    2
    4
    0
    2
    0
    0
    Onychomycosis
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    3 / 16 (18.75%)
    0 / 16 (0.00%)
    8 / 45 (17.78%)
    2 / 10 (20.00%)
    3 / 15 (20.00%)
    8 / 45 (17.78%)
         occurrences all number
    1
    0
    3
    0
    9
    2
    5
    8
    Sinusitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 16 (12.50%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    Pharyngitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    2 / 16 (12.50%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    0
    0
    Acarodermatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    Body tinea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    1 / 15 (6.67%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    3 / 45 (6.67%)
    0 / 10 (0.00%)
    2 / 15 (13.33%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    2
    1
    Pelvic inflammatory disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Tinea versicolour
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    1 / 16 (6.25%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    0
    5
    Iron deficiency
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 16 (6.25%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    1 / 45 (2.22%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    0 / 45 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 16 (0.00%)
    0 / 16 (0.00%)
    0 / 45 (0.00%)
    0 / 10 (0.00%)
    0 / 15 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Aug 2022
    The main reason for this amendment was to update the reporting duration of AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention from up to the study end (Day 1 to Day 337) to 28 days after third study intervention administration (Day 1 to Day 197), a new secondary endpoint was added to include number of participants with AEs/SAEs leading to withdrawal from the study from 28 days after third study intervention administration (Day 197) up to Day 337 and the end of study information (in case where the end of study would be the date of last testing results revealed) was updated to be achieved no later than 8 months after last subject last visit instead of 6 months after third study intervention administration.
    08 Jun 2023
    The main reason for this amendment was to update tertiary endpoint related to seroresponse to improve the seroresponse endpoints and to optimize the number of samples to be tested from Stage 2 for functionality of antibodies, clarification was added on taking immunogenicity sample and safety follow-up for participant discontinued due to AE to avoid protocol deviations arising from taking immunogenicity samples from discontinued participants observed in Stage 1 due to lack of clarity and justification for collection of race (ethnic background) data was added.

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

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

    European Medicines Agency © 1995-Mon Jan 12 02:07:09 CET 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA