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   44367   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 staged Phase I/II observer-blind, randomised, controlled, multi-country study to evaluate the safety, reactogenicity, and immune responses to the GVGH altSonflex1-2-3 vaccine against S. sonnei and S. flexneri, serotypes 1b, 2a, and 3a, in adults in Europe (Stage 1) followed by age de-escalation from adults to children and infants, and dose-finding in infants in Africa (Stage 2)

    Summary
    EudraCT number
    		 2021-000891-12
    Trial protocol
    		 BE  
    Global end of trial date
    24 Jun 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
    212149
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05073003
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    79 New Oxford Street, London, WC1A 1DG, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 44 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 Jul 2025
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Jun 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of the current clinical study is to evaluate, for the first time in humans (FTIH), the safety and immunogenicity of the altSonflex1-2-3 candidate vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a.
    Protection of trial subjects
    Participants will be closely monitored for any symptoms of anaphylaxis. Medical treatment will be readily available in case of anaphylactic reactions following vaccine/control/placebo administration. Safe blood sampling procedures will be applied by appropriately trained and qualified staff to minimise distress and sampling errors
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Oct 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Kenya: 449
    Country: Number of subjects enrolled
    Belgium: 102
    Worldwide total number of subjects
    551
    EEA total number of subjects
    102
    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)
    389
    Children (2-11 years)
    40
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    122
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Out of 551 participants enrolled, 550 started the study and were included in the Exposed set.

    Pre-assignment
    Screening details
    		 As pre-specified in the Statistical Analysis Plan (SAP), the participants that received placebo in Stage 1 were pooled for all analyses (demography, immunogenicity and safety).

    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 Adults: altSonflex1-2-3 High Dose Group 1
    Arm description
    		 European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AltSonflex1-2-3 High Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2
    Arm description
    		 European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 169.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AltSonflex1-2-3 High Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 1 Adults: Placebo Group
    Arm description
    		 European participants 18-50 years of age were randomized to receive 1 dose of Placebo on Day 1 and on Day 85 or 169. All participants in Step 1 that received placebo were pooled, as pre-specified in Statistical Analysis Plan.
    Arm type
    		 Placebo

    Investigational medicinal product name
    altSonflex Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age (stage 1)

    Arm title
    		 Stage 2 Adults: altSonflex1-2-3 High Dose
    Arm description
    		 African participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AltSonflex1-2-3 High Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Adults: Control
    Arm description
    		 African participants 18-50 years of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of BOOSTRIX as comparator Day 85.
    Arm type
    		 Active comparator

    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 in adults 18-50 years of age (stage 2)

    Investigational medicinal product name
    Menveo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age

    Arm title
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose
    Arm description
    		 African participants 24-59 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1 and Day 85.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AltSonflex1-2-3 Medium Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Children: altSonflex1-2-3 High Dose
    Arm description
    		 African participants 24-59 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AltSonflex1-2-3 High Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Children: Control
    Arm description
    		 African participants 24-59 months of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of TYPHIM VI as comparator on Day 85.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Typhim-Vi
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in children 24-59 months of age

    Investigational medicinal product name
    Menveo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose
    Arm description
    		 African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. The measles-rubella vaccine (MR-VAC) was administered on Day 29 and Day 281.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in children 24-59 months of age

    Investigational medicinal product name
    AltSonflex1-2-3 Low Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose
    Arm description
    		 African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Investigational medicinal product name
    AltSonflex1-2-3 Medium Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose
    Arm description
    		 African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.
    Arm type
    		 Experimental

    Investigational medicinal product name
    AltSonflex1-2-3 High Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants safety cohort: Control
    Arm description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Menveo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Investigational medicinal product name
    INFANRIX HEXA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in infants 9 months of age

    Arm title
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose
    Arm description
    		 African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Investigational medicinal product name
    AltSonflex1-2-3 Low Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose
    Arm description
    		 African participants 9 months of age were randomized to receive a medium (Med) dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Investigational medicinal product name
    AltSonflex1-2-3 Medium Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose
    Arm description
    		 African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Investigational medicinal product name
    AltSonflex1-2-3 High Dose
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

    Arm title
    		 Stage 2 Infants dose-finding cohort: Control
    Arm description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Menveo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age

    Investigational medicinal product name
    INFANRIX HEXA
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose in infants 9 months of age

    Investigational medicinal product name
    MR-Vac
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 doses in infants 9 months of age

    Number of subjects in period 1 [1]
    		Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Started
    34
    34
    34
    10
    10
    10
    10
    20
    10
    10
    10
    30
    82
    81
    83
    82
    Completed
    29
    34
    28
    10
    10
    10
    10
    20
    9
    8
    10
    27
    69
    71
    73
    71
    Not completed
    5
    0
    6
    0
    0
    0
    0
    0
    1
    2
    0
    3
    13
    10
    10
    11
         Migrated / moved from the study area
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    1
    2
    2
    2
    -
         Not Specified
    2
    -
    4
    -
    -
    -
    -
    -
    1
    -
    -
    -
    1
    -
    1
    1
         Consent withdrawal, not due to an (S)AE
    1
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    2
    9
    4
    5
    5
         Lost to follow-up
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    3
    2
    5
         Adverse Events (including death)
    2
    -
    2
    -
    -
    -
    -
    -
    -
    -
    -
    -
    -
    1
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of 551 participants enrolled, 550 started the study and were included in the Exposed set.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Stage 1 Adults: altSonflex1-2-3 High Dose Group 1
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 1 Adults: altSonflex1-2-3 High Dose Group 2
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 169.

    Reporting group title
    Stage 1 Adults: Placebo Group
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive 1 dose of Placebo on Day 1 and on Day 85 or 169. All participants in Step 1 that received placebo were pooled, as pre-specified in Statistical Analysis Plan.

    Reporting group title
    Stage 2 Adults: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 2 Adults: Control
    Reporting group description
    		 African participants 18-50 years of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of BOOSTRIX as comparator Day 85.

    Reporting group title
    Stage 2 Children: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 2 Children: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 2 Children: Control
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of TYPHIM VI as comparator on Day 85.

    Reporting group title
    Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. The measles-rubella vaccine (MR-VAC) was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants safety cohort: Control
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a medium (Med) dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants dose-finding cohort: Control
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control Total
    Number of subjects
    		 34 34 34 10 10 10 10 20 10 10 10 30 82 81 83 82 550
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0 0 10 10 20 10 10 10 30 82 81 83 82 428
        Between 18 and 65 years
    		 34 34 34 10 10 0 0 0 0 0 0 0 0 0 0 0 122
        >=65 years
    		 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
    Sex: Female, Male
    Units: Participants
        Male
    		 6 7 7 4 4 6 6 9 3 5 6 14 50 38 42 33 240
        Female
    		 28 27 27 6 6 4 4 11 7 5 4 16 32 43 41 49 310
    Race/Ethnicity, Customized
    Units: Subjects
        BLACK OR AFRICAN AMERICAN
    		 0 0 0 10 10 10 10 20 10 10 10 30 82 81 83 82 448
        WHITE
    		 34 34 34 0 0 0 0 0 0 0 0 0 0 0 0 0 102

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Stage 1 Adults: altSonflex1-2-3 High Dose Group 1
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 1 Adults: altSonflex1-2-3 High Dose Group 2
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 169.

    Reporting group title
    Stage 1 Adults: Placebo Group
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive 1 dose of Placebo on Day 1 and on Day 85 or 169. All participants in Step 1 that received placebo were pooled, as pre-specified in Statistical Analysis Plan.

    Reporting group title
    Stage 2 Adults: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 2 Adults: Control
    Reporting group description
    		 African participants 18-50 years of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of BOOSTRIX as comparator Day 85.

    Reporting group title
    Stage 2 Children: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 2 Children: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85.

    Reporting group title
    Stage 2 Children: Control
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of TYPHIM VI as comparator on Day 85.

    Reporting group title
    Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. The measles-rubella vaccine (MR-VAC) was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants safety cohort: Control
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a medium (Med) dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants dose-finding cohort: Control
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.

    Subject analysis set title
    Stage 2 Infants: altSonflex1-2-3 Low Dose Pooled
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered either on Day 1 and Day 253 or on Day 29 and Day 281. This group was obtained by pooling the Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose group and the Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose group.

    Subject analysis set title
    Stage 2 Infants: altSonflex1-2-3 Medium Dose Pooled
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered either on Day 1 and Day 253 or on Day 29 and Day 281. This group was obtained by pooling the Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose group and the Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Medium Dose group.

    Subject analysis set title
    Stage 2 Infants: altSonflex1-2-3 High Dose Pooled
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered either on Day 1 and Day 253 or on Day 29 and Day 281. This group was obtained by pooling the Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose group and the Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose group.

    Primary: Stage 2: Geometric mean concentrations (GMCs) of Anti-serotype specific Shigella lipopolysaccharide (LPS)/O-Antigen (OAg) serum immunoglobulin G (IgG) in participants 9 months of age in Africa

    		 Close Top of page
    End point title
    		 Stage 2: Geometric mean concentrations (GMCs) of Anti-serotype specific Shigella lipopolysaccharide (LPS)/O-Antigen (OAg) serum immunoglobulin G (IgG) in participants 9 months of age in Africa
    End point description
    Anti-serotype specific Shigella LPS/OAg serum IgG GMCs were measured by enzyme-linked immunosorbent assay (ELISA) and expressed in ELISA units per milliliter (EU/mL) of serum. S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes were tested. The analysis was performed on the Per protocol set (PPS) for Stage 2 Infants which 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 & without prohibited concomitant medication/vaccination. The PPS for immunogenicity was defined by time point. Due to the PPS for Stage 2 Infants – dose finding cohort having less than the planned 72 participants per group, the Stage 2 Infants safety cohort and dose-finding cohort were pooled for this analysis. As per protocol, statistical analysis was performed only for the S. sonnei serotype, comparing medium vs low dose.
    End point type
    Primary
    End point timeframe
    At Day 281 (28 days after the third study intervention)
    End point values
    		 Stage 2 Infants: altSonflex1-2-3 Low Dose Pooled Stage 2 Infants: altSonflex1-2-3 Medium Dose Pooled Stage 2 Infants: altSonflex1-2-3 High Dose Pooled
    Number of subjects analysed
    75
    72
    80
    Units: ELISA units per milliliter (EU/mL)
    geometric mean (confidence interval 95%)
        S. sonnei Ab IgG
    379.3 (81.4 to 1766.5)
    463.5 (95.0 to 2261.3)
    457.6 (94.7 to 2211.3)
        S. flexneri 1b Ab IgG
    51.1 (39.3 to 66.4)
    32.1 (25.6 to 40.4)
    35.6 (28.3 to 44.8)
        S. flexneri 2a Ab IgG
    177.8 (57.4 to 550.6)
    135.3 (34.0 to 537.9)
    173.8 (62.4 to 484.0)
        S. flexneri 3a Ab IgG
    32.6 (6.1 to 173.2)
    24.4 (4.8 to 125.4)
    27.5 (5.0 to 152.2)
    Statistical analysis title
    		 Ratio of Geometric mean concentrations (GMR)
    Statistical analysis description
    To identify the preferred dose of S. sonnei component of the vaccine (medium vs. low) for infants 9 months of age in Africa. The statistical tests to identify the preferred dose among the 3 different dose levels (Dose A, Dose B, and Dose C) in infants were defined according to GMCs dose-response shapes of each of the 4 components as measured by GVGH ELISA. The selection strategy had been predefined for each of the possible scenarios of the dose-response shapes.
    Comparison groups
    Stage 2 Infants: altSonflex1-2-3 Low Dose Pooled v Stage 2 Infants: altSonflex1-2-3 Medium Dose Pooled
    Number of subjects included in analysis
    147
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 = 0.273
    Method
    		 t-test, 2-sided
    Parameter type
    		 Geometric Mean Concentration Ratio
    Point estimate
    1.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.85
         upper limit
    		 1.75
    Notes
    [1] - Results are based on a linear mixed model with fixed effect for treatment, timepoint, baseline value, treatment*timepoint, random effect for cohort and a repeated timepoint effect within a participant under an unstructured covariance matrix. Model assumes unequal variances between treatment groups. Restricted maximum likelihood was used to estimate the variance components, Kenward-Roger approximation was used to calculate the degrees of freedom.

    Primary: Stage 1: Number of participants 18 to 50 years of age in Europe with solicited administration site events

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age in Europe with solicited administration site events [2] [3]
    End point description
    The solicited administration site events assessed were erythema, pain and swelling. 9999 = data not available. The analysis was performed on the Solicited Safety Set for Stage 1 Adults which included all participants who received at least 1 dose of the study intervention, who have solicited safety data. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 169 [depending on the vaccination schedule])
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [3] - 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 analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        Erythema, Vaccination at Day 1
    4
    6
    1
        Erythema, Vaccination at Day 85
    2
    9999
    9999
        Erythema, Vaccination at 169
    9999
    4
    9999
        Erythema, Vaccination at Day 85/169
    9999
    9999
    0
        Pain, Vaccination at Day 1
    32
    33
    16
        Pain, Vaccination at Day 85
    22
    9999
    9999
        Pain, Vaccination at Day 169
    9999
    31
    9999
        Pain, Vaccination at Day 85/169
    9999
    9999
    8
        Swelling, Vaccination at Day 1
    2
    7
    0
        Swelling, Vaccination at Day 85
    5
    9999
    9999
        Swelling, Vaccination at 169
    9999
    5
    9999
        Swelling, Vaccination at Day 85/169
    9999
    9999
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of adults 18 to 50 years of age in Europe with solicited systemic events

    		 Close Top of page
    End point title
    		 Stage 1: Number of adults 18 to 50 years of age in Europe with solicited systemic events [4] [5]
    End point description
    The solicited systemic event assessed was fever. Fever is defined as temperature equal to or above (=>) 38.0°C. N = number of participants analyzed in the specific time frame. 9999 = data not available. The analysis was performed on the Solicited Safety Set for Stage 1 Adults. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 169 [depending on the vaccination schedule])
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [5] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        Within 7 days after vaccination at Day 1
    0
    1
    0
        Within 7 days after vaccination at Day 85
    2
    9999
    9999
        Within 7 days after vaccination at Day 169
    9999
    1
    9999
        Within 7 days after vaccination at Day 85/169
    9999
    9999
    1
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants 18 to 50 years of age in Europe with Serious adverse events (SAEs)

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age in Europe with Serious adverse events (SAEs) [6] [7]
    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. 9999 = data not available. The analysis was performed on the Exposed Set for Stage 1 Adults which included all participants who received at least 1 dose of the study intervention. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 113 and/or Day 197
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [7] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        From Day 1 to Day 113
    0
    9999
    9999
        From Day 1 to Day 197
    9999
    1
    9999
        From Day 1 to Day 113/197
    9999
    9999
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants 18 to 50 years of age in Europe with unsolicited adverse events (AEs)

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age in Europe with unsolicited adverse events (AEs) [8] [9]
    End point description
    An unsolicited AE is defined as 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 adverse event. 9999 = data not available. The analysis was performed on the Unsolicited Safety Set for Stage 1 Adults which included all participants who received at least 1 dose of the study intervention that reported having/not having unsolicited AEs. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group.
    End point type
    Primary
    End point timeframe
    Within 28 days after each study intervention (administered at at Day 1, Day 85 and Day 169 [depending on the vaccination schedule])
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [9] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        Within 28 days after vaccination at Day 1
    25
    21
    25
        Within 28 days after vaccination at Day 85
    14
    9999
    9999
        Within 28 days after vaccination at Day 169
    9999
    14
    9999
        Within 28 days after vaccination at Day 85/169
    9999
    9999
    12
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention [10] [11]
    End point description
    Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 1 Adults.
    End point type
    Primary
    End point timeframe
    At Day 8
    Notes
    [10] - 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.
    [11] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        ALT, Within, Within
    32
    33
    30
        ALT, Within, Above
    1
    0
    1
        ALT, Above, Within
    1
    0
    1
        ALT, Above, Above
    0
    1
    2
        AST, Within, Within
    31
    33
    31
        AST, Within, Above
    0
    0
    3
        AST, Above, Within
    3
    0
    0
        AST, Above, Above
    0
    1
    0
        Creatinine, Within, Within
    33
    34
    34
        Creatinine, Above, Above
    1
    0
    0
        Basophils, Below, Below
    0
    0
    1
        Basophils, Below, Within
    3
    0
    1
        Basophils, Within, Below
    0
    0
    1
        Basophils, Within, Within
    31
    33
    31
        Basophils, Above, Within
    0
    1
    0
        Eosinophils, Below, Within
    1
    1
    1
        Eosinophils, Within, Below
    0
    2
    0
        Eosinophils, Within, Within
    32
    30
    31
        Eosinophils, Within, Above
    0
    0
    1
        Eosinophils, Above, Within
    1
    0
    0
        Eosinophils, Above, Above
    0
    1
    1
        Erythrocytes, Below, Below
    1
    0
    0
        Erythrocytes, Below, Within
    1
    0
    0
        Erythrocytes, Within, Below
    0
    1
    0
        Erythrocytes, Within, Within
    32
    32
    33
        Erythrocytes, Above, Within
    0
    1
    1
        Haematocrit, Below, Below
    0
    1
    0
        Haematocrit, Below, Within
    1
    0
    1
        Haematocrit, Within, Within
    32
    32
    33
        Haematocrit, Above, Within
    1
    0
    0
        Haematocrit, Above, Above
    0
    1
    0
        Haemoglobin, Below, Below
    1
    1
    0
        Haemoglobin, Below, Within
    2
    1
    0
        Haemoglobin, Within, Below
    0
    1
    0
        Haemoglobin, Within, Within
    30
    28
    33
        Haemoglobin, Within, Above
    0
    1
    0
        Haemoglobin, Above, Within
    1
    1
    1
        Haemoglobin, Above, Above
    0
    1
    0
        Lymphocytes, Below, Below
    2
    2
    0
        Lymphocytes, Below, Within
    1
    0
    1
        Lymphocytes, Within, Within
    31
    32
    31
        Lymphocytes, Within, Above
    0
    0
    2
        Monocytes, Below, Within
    0
    1
    1
        Monocytes, Within, Below
    1
    0
    0
        Monocytes, Within, Within
    33
    33
    31
        Monocytes, Above, Within
    0
    0
    1
        Monocytes, Above, Above
    0
    0
    1
        Neutrophils, Below, Within
    1
    0
    1
        Neutrophils, Below, Above
    1
    0
    0
        Neutrophils, Within, Below
    0
    2
    1
        Neutrophils, Within, Within
    28
    28
    32
        Neutrophils, Within, Above
    1
    3
    0
        Neutrophils, Above, Within
    3
    1
    0
        Platelets, Below, Within
    0
    1
    2
        Platelets, Within, Within
    29
    28
    29
        Platelets, Within, Above
    0
    3
    1
        Platelets, Above, Within
    1
    0
    1
        Platelets, Above, Above
    4
    2
    1
        WBC, Below, Within
    2
    1
    2
        WBC, Within, Below
    1
    4
    0
        WBC, Within, Within
    30
    29
    32
        WBC, Within, Above
    1
    0
    0
    No statistical analyses for this end point

    Primary: Stage 1: Number of participants 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention [12] [13]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 85/Day 169 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 1 Adults.
    End point type
    Primary
    End point timeframe
    At Day 92 (Stage 1 Adults: altSonflex1-2-3 High Dose Group 1), at Day 176 (Stage 1 Adults: altSonflex1-2-3 High Dose Group 2) and at Day 92/Day 176 (Stage 1 Adults: Placebo Group)
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [13] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    29
    34
    28
    Units: Participants
        ALT, Within, Within
    26
    32
    26
        ALT, Within, Above
    1
    0
    0
        ALT, Above, Within
    1
    1
    1
        ALT, Above, Above
    1
    1
    1
        AST, Within, Within
    27
    32
    27
        AST, Within, Above
    1
    0
    0
        AST, Above, Within
    1
    1
    1
        AST, Above, Above
    0
    1
    0
        Creatinine, Within, Within
    28
    34
    27
        Creatinine, Within, Above
    0
    0
    1
        Creatinine, Above, Above
    1
    0
    0
        Basophils, Below, Below
    0
    0
    1
        Basophils, Below, Within
    1
    1
    1
        Basophils, Within, Below
    2
    0
    0
        Basophils, Within, Within
    26
    33
    25
        Basophils, Within, Above
    0
    0
    1
        Eosinophils, Below, Below
    0
    2
    0
        Eosinophils, Within, Below
    1
    0
    1
        Eosinophils, Within, Within
    25
    30
    24
        Eosinophils, Within, Above
    1
    1
    1
        Eosinophils, Above, Within
    0
    0
    1
        Eosinophils, Above, Above
    2
    1
    1
        Erythrocytes, Within, Below
    0
    0
    1
        Erythrocytes, Within, Within
    29
    32
    27
        Erythrocytes, Above, Within
    0
    1
    0
        Erythrocytes, Above, Above
    0
    1
    0
        Haematocrit, Below, Below
    0
    1
    0
        Haematocrit, Within, Below
    0
    1
    0
        Haematocrit, Within, Within
    29
    31
    28
        Haematocrit, Above, Within
    0
    1
    0
        Haemoglobin, Below, Below
    0
    1
    0
        Haemoglobin, Below, Within
    1
    0
    0
        Haemoglobin, Within, Below
    0
    1
    0
        Haemoglobin, Within, Within
    27
    30
    28
        Haemoglobin, Within, Above
    1
    0
    0
        Haemoglobin, Above, Within
    0
    2
    0
        Lymphocytes, Below, Below
    1
    1
    1
        Lymphocytes, Below, Within
    2
    2
    0
        Lymphocytes, Within, Below
    0
    3
    0
        Lymphocytes, Within, Within
    25
    28
    27
        Lymphocytes, Within, Above
    1
    0
    0
        Monocytes, Below, Below
    0
    0
    1
        Monocytes, Below, Within
    1
    1
    1
        Monocytes, Within, Within
    28
    30
    23
        Monocytes, Within, Above
    0
    2
    0
        Monocytes, Above, Within
    0
    1
    3
        Neutrophils, Below, Below
    0
    0
    1
        Neutrophils, Below, Within
    2
    3
    0
        Neutrophils, Within, Below
    1
    0
    1
        Neutrophils, Within, Within
    26
    26
    22
        Neutrophils, Within, Above
    0
    2
    1
        Neutrophils, Above, Within
    0
    2
    2
        Neutrophils, Above, Above
    0
    1
    1
        Platelets, Below, Within
    1
    0
    1
        Platelets, Within, Below
    1
    0
    1
        Platelets, Within, Within
    23
    29
    23
        Platelets, Within, Above
    1
    2
    3
        Platelets, Above, Within
    3
    0
    0
        Platelets, Above, Above
    0
    3
    0
        WBC, Below, Below
    1
    3
    1
        WBC, Below, Within
    2
    2
    0
        WBC, Within, Below
    1
    0
    1
        WBC, Within, Within
    25
    26
    24
        WBC, Within, Above
    0
    3
    0
        WBC, Above, Within
    0
    0
    1
        WBC, Above, Above
    0
    0
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 18 to 50 years of age in Africa with solicited systemic events

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age in Africa with solicited systemic events [14] [15]
    End point description
    The solicited systemic event assessed was fever. Fever is defined as temperature equal to or above (=>) 38.0°C. The analysis was performed on the Solicited Safety Set for Stage 2 Adults.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [15] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        Vaccination at Day 1
    0
    0
        Vaccination at Day 85
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 18 to 50 years of age in Africa with solicited administration site events

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age in Africa with solicited administration site events [16] [17]
    End point description
    The solicited administration site events assessed were pain, erythema, and swelling. The analysis was performed on the Solicited Safety Set for Stage 2 Adults.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [17] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        Pain, Vaccination at Day 1
    5
    2
        Pain, Vaccination at Day 85
    4
    3
        Erythema, Vaccination at Day 1
    0
    0
        Erythema, Vaccination at Day 85
    0
    0
        Swelling, Vaccination at Day 1
    0
    0
        Swelling, Vaccination at Day 85
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 18 to 50 years of age in Africa with unsolicited adverse events (AEs)

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age in Africa with unsolicited adverse events (AEs) [18] [19]
    End point description
    An unsolicited AE is defined as 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 adverse event. The analysis was performed on the Unsolicited Safety Set for Stage 2 Adults.
    End point type
    Primary
    End point timeframe
    Within 28 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [19] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        Vaccination at Day 1
    2
    1
        Vaccination at Day 85
    2
    2
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 18 to 50 years of age in Africa with Serious adverse events (SAEs)

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age in Africa with Serious adverse events (SAEs) [20] [21]
    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. The analysis was performed on the Exposed Set for Stage 2 Adults.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 113
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [21] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention [22] [23]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Adults.
    End point type
    Primary
    End point timeframe
    At Day 8
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    [23] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        ALT, Within, Below
    0
    1
        ALT, Within, Within
    10
    9
        AST, Within, Within
    10
    10
        Creatinine, Below, Below
    6
    6
        Creatinine, Below, Within
    1
    0
        Creatinine, Within, Below
    0
    1
        Creatinine, Within, Within
    3
    3
        Basophils, Within, Within
    10
    10
        Eosinophils, Within, Below
    0
    1
        Eosinophils, Within, Within
    10
    9
        Erythrocytes, Within, Within
    10
    10
        Haematocrit, Within, Within
    10
    10
        Haemoglobin, Within, Within
    10
    10
        Lymphocytes, Below, Within
    0
    2
        Lymphocytes, Within, Within
    9
    8
        Lymphocytes, Above, Above
    1
    0
        Monocytes, Within, Within
    9
    7
        Monocytes, Within, Above
    0
    1
        Monocytes, Above, Above
    1
    2
        Neutrophils, Within, Within
    9
    9
        Neutrophils, Within, Above
    1
    1
        Platelets, Within, Within
    10
    10
        WBC, Below, Within
    0
    1
        WBC, Within, Within
    8
    8
        WBC, Within, Above
    1
    1
        WBC, Above, Above
    1
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention [24] [25]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 85 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Adults.
    End point type
    Primary
    End point timeframe
    At Day 92
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [25] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        ALT, Within, Within
    9
    10
        ALT, Within, Above
    1
    0
        AST, Below, Within
    1
    0
        AST, Within, Within
    8
    10
        AST, Within, Above
    1
    0
        Creatinine, Below, Below
    6
    4
        Creatinine, Within, Below
    1
    2
        Creatinine, Within, Within
    3
    4
        Basophils, Within, Within
    10
    10
        Eosinophils, Below, Within
    0
    1
        Eosinophils, Within, Within
    10
    9
        Erythrocytes, Within, Within
    10
    10
        Haematocrit, Within, Within
    10
    10
        Haemoglobin, Within, Within
    10
    10
        Lymphocytes, Below, Within
    0
    1
        Lymphocytes, Within, Within
    9
    9
        Lymphocytes, Above, Above
    1
    0
        Monocytes, Within, Within
    7
    9
        Monocytes, Within, Above
    2
    1
        Monocytes, Above, Within
    1
    0
        Neutrophils, Within, Within
    8
    10
        Neutrophils, Within, Above
    1
    0
        Neutrophils, Above, Within
    1
    0
        Platelets, Within, Within
    9
    10
        Platelets, Within, Above
    1
    0
        WBC, Within, Within
    8
    10
        WBC, Within, Above
    1
    0
        WBC, Above, Within
    1
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 24 to 59 months of age in Africa with solicited administration site events

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age in Africa with solicited administration site events [26] [27]
    End point description
    The solicited administration site events assessed were erythema, pain, and swelling. The analysis was performed on the Solicited Safety Set for Stage Children. The analysis was performed on the Solicited Safety Set for Stage 2 Children.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        Erythema, Vaccination at Day 1
    1
    1
    0
        Erythema, Vaccination at Day 85
    1
    0
    0
        Pain, Vaccination at Day 1
    6
    2
    3
        Pain, Vaccination at Day 85
    7
    2
    3
        Swelling, Vaccination at Day 1
    1
    1
    0
        Swelling, Vaccination at Day 85
    1
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 24 to 59 months of age in Africa with solicited systemic events

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age in Africa with solicited systemic events [28] [29]
    End point description
    The solicited systemic event assessed was fever. Fever is defined as temperature equal to or above (=>) 38.0°C. The analysis was performed on the Solicited Safety Set for Stage 2: Children.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [29] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        Vaccination at Day 1
    1
    1
    0
        Vaccination at Day 85
    1
    2
    3
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 24 to 59 months of age in Africa with unsolicited adverse events (AEs)

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age in Africa with unsolicited adverse events (AEs) [30] [31]
    End point description
    An unsolicited AE is defined as 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 adverse event. The analysis was performed on the Unsolicited Safety Set for Stage 2: Children.
    End point type
    Primary
    End point timeframe
    Within 28 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [30] - 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.
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        Vaccination at Day 1
    4
    3
    8
        Vaccination at Day 85
    2
    0
    3
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 24 to 59 months of age in Africa with Serious adverse events (SAEs)

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age in Africa with Serious adverse events (SAEs) [32] [33]
    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. The analysis was performed on the Exposed Set for Stage 2 Children.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 113
    Notes
    [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
    0
    0
    0
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention [34] [35]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Children.
    End point type
    Primary
    End point timeframe
    At Day 8
    Notes
    [34] - 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.
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        ALT, Within, Within
    8
    9
    16
        ALT, Within, Above
    0
    1
    1
        ALT, Above, Within
    0
    0
    2
        ALT, Above, Above
    2
    0
    1
        AST, Within, Within
    8
    10
    20
        AST, Above, Within
    2
    0
    0
        Creatinine, Below, Below
    8
    9
    17
        Creatinine, Below, Within
    1
    0
    0
        Creatinine, Within, Below
    1
    1
    1
        Creatinine, Within, Within
    0
    0
    1
        Creatinine, Above, Within
    0
    0
    1
        Basophils, Within, Below
    0
    0
    1
        Basophils, Within, Within
    9
    10
    16
        Basophils, Within, Above
    1
    0
    2
        Basophils, Above, Within
    0
    0
    1
        Eosinophils, Below, Within
    1
    0
    0
        Eosinophils, Within, Below
    0
    0
    1
        Eosinophils, Within, Within
    5
    6
    12
        Eosinophils, Within, Above
    0
    0
    1
        Eosinophils, Above, Within
    0
    1
    1
        Eosinophils, Above, Above
    4
    3
    5
        Erythrocytes, Within, Within
    8
    9
    12
        Erythrocytes, Within, Above
    1
    0
    0
        Erythrocytes, Above, Within
    0
    1
    5
        Erythrocytes, Above, Above
    1
    0
    3
        Haematocrit, Below, Below
    0
    1
    0
        Haematocrit, Within, Within
    8
    7
    14
        Haematocrit, Within, Above
    0
    0
    1
        Haematocrit, Above, Within
    2
    2
    5
        Haemoglobin, Below, Below
    0
    1
    0
        Haemoglobin, Below, Within
    1
    0
    0
        Haemoglobin, Within, Below
    0
    0
    1
        Haemoglobin, Within, Within
    7
    7
    18
        Haemoglobin, Above, Within
    1
    2
    0
        Haemoglobin, Above, Above
    1
    0
    1
        Lymphocytes, Within, Within
    7
    7
    8
        Lymphocytes, Within, Above
    1
    0
    2
        Lymphocytes, Above, Within
    2
    1
    7
        Lymphocytes, Above, Above
    0
    2
    3
        Monocytes, Within, Within
    9
    8
    13
        Monocytes, Within, Above
    1
    2
    3
        Monocytes, Above, Within
    0
    0
    1
        Monocytes, Above, Above
    0
    0
    3
        Neutrophils, Below, Below
    0
    0
    1
        Neutrophils, Below, Within
    2
    0
    2
        Neutrophils, Within, Below
    2
    0
    1
        Neutrophils, Within, Within
    6
    10
    16
        Platelets, Within, Within
    1
    3
    4
        Platelets, Within, Above
    5
    4
    2
        Platelets, Above, Within
    0
    0
    4
        Platelets, Above, Above
    4
    3
    10
        WBC, Below, Within
    1
    0
    0
        WBC, Within, Within
    9
    10
    19
        WBC, Above, Above
    0
    0
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention [36] [37]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 85 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Children.
    End point type
    Primary
    End point timeframe
    At Day 92
    Notes
    [36] - 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.
    [37] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        ALT, Within, Within
    9
    5
    15
        ALT, Within, Above
    0
    0
    2
        ALT, Above, Within
    0
    2
    1
        ALT, Above, Above
    1
    3
    2
        AST, Within, Within
    10
    10
    19
        AST, Within, Above
    0
    0
    1
        Creatinine, Below, Below
    10
    8
    18
        Creatinine, Within, Below
    0
    2
    2
        Basophils, Within, Within
    9
    9
    20
        Basophils, Above, Within
    1
    0
    0
        Basophils, Above, Above
    0
    1
    0
        Eosinophils, Within, Below
    1
    0
    0
        Eosinophils, Within, Within
    6
    8
    16
        Eosinophils, Within, Above
    1
    0
    1
        Eosinophils, Above, Above
    2
    2
    3
        Erythrocytes, Below, Within
    1
    0
    0
        Erythrocytes, Within, Within
    7
    8
    17
        Erythrocytes, Within, Above
    1
    0
    1
        Erythrocytes, Above, Within
    0
    1
    0
        Erythrocytes, Above, Above
    1
    1
    2
        Haematocrit, Below, Below
    1
    0
    0
        Haematocrit, Below, Within
    0
    0
    1
        Haematocrit, Within, Within
    9
    10
    19
        Haemoglobin, Below, Below
    1
    0
    1
        Haemoglobin, Within, Below
    0
    0
    1
        Haemoglobin, Within, Within
    9
    8
    18
        Haemoglobin, Above, Within
    0
    2
    0
        Lymphocytes, Within, Within
    7
    6
    14
        Lymphocytes, Within, Above
    0
    0
    2
        Lymphocytes, Above, Within
    3
    2
    3
        Lymphocytes, Above, Above
    0
    2
    1
        Monocytes, Below, Within
    0
    1
    0
        Monocytes, Within, Within
    9
    7
    13
        Monocytes, Within, Above
    1
    0
    2
        Monocytes, Above, Within
    0
    0
    4
        Monocytes, Above, Above
    0
    2
    1
        Neutrophils, Below, Below
    2
    0
    0
        Neutrophils, Below, Within
    1
    0
    1
        Neutrophils, Within, Below
    0
    0
    1
        Neutrophils, Within, Within
    5
    10
    18
        Neutrophils, Within, Above
    2
    0
    0
        Platelets, Within, Within
    3
    3
    7
        Platelets, Within, Above
    1
    1
    5
        Platelets, Above, Within
    2
    1
    2
        Platelets, Above, Above
    4
    5
    6
        WBC, Below, Within
    2
    0
    0
        WBC, Within, Within
    7
    10
    19
        WBC, Above, Above
    1
    0
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with solicited administration site events - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with solicited administration site events - Infants safety cohort [38] [39]
    End point description
    The solicited administration site events assessed were erythema, pain, and swelling. N = number of participants analyzed in the specific time frame. The analysis was performed on the Solicited Safety Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1 and Day 85)
    Notes
    [38] - 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.
    [39] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        Erythema, Vaccination at Day 1
    0
    0
    3
    1
        Erythema, Vaccination at Day 85
    0
    1
    2
    0
        Erythema, Vaccination at Day 253
    0
    0
    4
    0
        Pain, Vaccination at Day 1
    2
    3
    7
    3
        Pain, Vaccination at Day 85
    2
    3
    6
    3
        Pain, Vaccination at Day 253
    2
    4
    7
    6
        Swelling, Vaccination at Day 1
    0
    1
    4
    2
        Swelling, Vaccination at Day 85
    0
    1
    2
    1
        Swelling, Vaccination at Day 253
    1
    0
    5
    3
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with solicited administration site events - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with solicited administration site events - Infants dose-finding cohort [40] [41]
    End point description
    The solicited administration site events assessed were erythema, pain, and swelling. N = number of participants analyzed in the specific time frame. The analysis was performed on the Solicited Safety Set for Stage 2 Infants, dose-finding cohort.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
    Notes
    [40] - 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.
    [41] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        Erythema, Vaccination at Day 1
    16
    9
    21
    9
        Erythema, Vaccination at Day 85
    11
    12
    11
    4
        Erythema, Vaccination at Day 253
    6
    7
    11
    8
        Pain, Vaccination at Day 1
    40
    42
    43
    14
        Pain, Vaccination at Day 85
    34
    36
    43
    20
        Pain, Vaccination at Day 253
    27
    39
    41
    26
        Swelling, Vaccination at Day 1
    21
    21
    21
    9
        Swelling, Vaccination at Day 85
    19
    20
    22
    2
        Swelling, Vaccination at Day 253
    15
    12
    17
    14
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with solicited systemic events - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with solicited systemic events - Infants safety cohort [42] [43]
    End point description
    The solicited systemic event is fever. Fever is defined as temperature equal to or above (=>) 38.0°C. The analysis was performed on the Solicited Safety Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
    Notes
    [42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [43] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        Vaccination at Day 1
    3
    1
    4
    5
        Vaccination at Day 85
    2
    1
    1
    2
        Vaccination at Day 253
    1
    2
    2
    4
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with solicited systemic events - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with solicited systemic events - Infants dose-finding cohort [44] [45]
    End point description
    The solicited systemic event is fever. Fever is defined as temperature equal to or above (=>) 38.0°C. The analysis was performed on the Solicited Safety Set for Stage 2 Infants, dose finding cohort.
    End point type
    Primary
    End point timeframe
    Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
    Notes
    [44] - 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.
    [45] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    80
    79
    82
    81
    Units: Participants
        Vaccination at Day 1
    27
    18
    23
    7
        Vaccination at Day 85
    17
    13
    10
    17
        Vaccination at Day 253
    21
    16
    22
    9
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with unsolicited adverse events (AEs) - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with unsolicited adverse events (AEs) - Infants dose-finding cohort [46] [47]
    End point description
    An unsolicited AE is defined as 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 adverse event. The analysis was performed on the Unsolicited Safety Set for Stage 2 Infants, dose-finding cohort.
    End point type
    Primary
    End point timeframe
    Within 28 days after each study intervention (administered at Day 1, Day 85 and Day 253)
    Notes
    [46] - 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.
    [47] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        Vaccination at Day 1
    35
    37
    34
    41
        Vaccination at Day 85
    23
    25
    31
    28
        Vaccination at Day 253
    21
    29
    31
    26
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with unsolicited adverse events (AEs) - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with unsolicited adverse events (AEs) - Infants safety cohort [48] [49]
    End point description
    An unsolicited AE is defined as 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 adverse event. The analysis was performed on the Unsolicited Safety Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    Within 28 days after each study intervention (administered at Day 1, Day 85 and Day 253)
    Notes
    [48] - 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.
    [49] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        Vaccination at Day 1
    2
    3
    4
    17
        Vaccination at Day 85
    1
    4
    6
    10
        Vaccination at Day 253
    4
    2
    4
    4
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention - Infants safety cohort [50] [51]
    End point description
    Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    At Day 8
    Notes
    [50] - 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.
    [51] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        ALT, Below, Within
    0
    0
    1
    0
        ALT, Within, Within
    10
    9
    9
    29
        ALT, Within, Above
    0
    0
    0
    1
        AST, Within, Within
    10
    9
    10
    30
        Creatinine, Below, Below
    10
    9
    10
    30
        Basophils, Within, Within
    8
    0
    10
    18
        Basophils, Within, Above
    1
    0
    0
    2
        Basophils, Above, Within
    1
    1
    0
    1
        Basophils, Above, Above
    0
    8
    0
    9
        Eosinophils, Within, Within
    10
    8
    10
    28
        Eosinophils, Above, Above
    0
    1
    0
    2
        Erythrocytes, Within, Within
    8
    9
    9
    24
        Erythrocytes, Within, Above
    0
    0
    1
    1
        Erythrocytes, Above, Within
    2
    0
    0
    1
        Erythrocytes, Above, Above
    0
    0
    0
    4
        Haematocrit, Below, Below
    1
    0
    0
    1
        Haematocrit, Below, Within
    1
    0
    1
    1
        Haematocrit, Within, Below
    1
    1
    0
    0
        Haematocrit, Within, Within
    7
    8
    8
    25
        Haematocrit, Within, Above
    0
    0
    1
    0
        Haematocrit, Above, Within
    0
    0
    0
    1
        Haematocrit, Above, Above
    0
    0
    0
    2
        Haemoglobin, Below, Below
    2
    0
    0
    1
        Haemoglobin, Below, Within
    1
    0
    1
    1
        Haemoglobin, Within, Below
    1
    3
    1
    4
        Haemoglobin, Within, Within
    6
    6
    6
    23
        Haemoglobin, Within, Above
    0
    0
    1
    1
        Haemoglobin, Above, Within
    0
    0
    1
    0
        Lymphocytes, Within, Within
    8
    5
    9
    15
        Lymphocytes, Within, Above
    1
    1
    1
    5
        Lymphocytes, Above, Within
    1
    1
    0
    3
        Lymphocytes, Above, Above
    0
    2
    0
    7
        Monocytes, Below, Below
    0
    1
    0
    0
        Monocytes, Below, Within
    0
    0
    1
    1
        Monocytes, Within, Within
    7
    7
    6
    23
        Monocytes, Within, Above
    0
    0
    1
    3
        Monocytes, Above, Within
    0
    1
    2
    2
        Monocytes, Above, Above
    3
    0
    0
    1
        Neutrophils, Below, Below
    0
    0
    0
    1
        Neutrophils, Below, Within
    2
    0
    2
    2
        Neutrophils, Within, Below
    1
    0
    0
    3
        Neutrophils, Within, Within
    6
    9
    8
    24
        Neutrophils, Above, Within
    1
    0
    0
    0
        Platelets, Within, Below
    0
    0
    0
    1
        Platelets, Within, Within
    1
    1
    2
    2
        Platelets, Within, Above
    2
    0
    4
    8
        Platelets, Above, Within
    3
    0
    0
    3
        Platelets, Above, Above
    4
    8
    4
    16
        WBC, Below, Within
    0
    0
    1
    1
        WBC, Within, Below
    0
    0
    0
    1
        WBC, Within, Within
    8
    7
    9
    22
        WBC, Within, Above
    1
    0
    0
    4
        WBC, Above, Within
    0
    1
    0
    0
        WBC, Above, Above
    1
    1
    0
    2
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with Serious adverse events (SAEs) - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with Serious adverse events (SAEs) - Infants dose-finding cohort [52] [53]
    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. Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. The analysis was performed on the Exposed Set for Stage 2 Infants, dose-finding cohort.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 281
    Notes
    [52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [53] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
    2
    1
    4
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with Serious adverse events (SAEs) - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with Serious adverse events (SAEs) - Infants safety cohort [54] [55]
    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. The analysis was performed on the Exposed Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    From Day 1 to Day 281
    Notes
    [54] - 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.
    [55] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
    0
    0
    0
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after first study intervention - Infants dose-finding cohort [56] [57]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Infants.
    End point type
    Primary
    End point timeframe
    At Day 8
    Notes
    [56] - 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.
    [57] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        ALT, Within, Within
    77
    75
    79
    80
        ALT, Within, Above
    1
    1
    2
    1
        ALT, Above, Within
    1
    0
    1
    0
        AST, Within, Within
    76
    76
    78
    81
        AST, Within, Above
    3
    0
    2
    0
        AST, Above, Within
    0
    0
    2
    0
        Creatinine, Below, Below
    79
    76
    81
    81
        Creatinine, Within, Below
    0
    0
    1
    0
        Potassium, Below, Within
    0
    0
    0
    1
        Potassium, Within, Below
    0
    0
    1
    0
        Potassium, Within, Within
    79
    76
    81
    78
        Potassium, Within, Above
    0
    0
    0
    1
        Potassium, Above, Within
    0
    0
    0
    1
        Sodium, Within, Within
    40
    35
    39
    37
        Sodium, Within, Above
    14
    20
    19
    19
        Sodium, Above, Within
    8
    11
    14
    14
        Sodium, Above, Above
    17
    10
    10
    11
        Urea, Below, Below
    31
    29
    36
    25
        Urea, Below, Within
    13
    13
    16
    14
        Urea, Within, Below
    10
    14
    11
    15
        Urea, Within, Within
    25
    20
    19
    27
        Basophils, Within, Within
    69
    70
    73
    68
        Basophils, Within, Above
    2
    2
    2
    5
        Basophils, Above, Within
    5
    4
    7
    6
        Basophils, Above, Above
    3
    0
    0
    2
        Eosinophils, Below, Within
    0
    2
    3
    1
        Eosinophils, Within, Below
    4
    3
    1
    3
        Eosinophils, Within, Within
    70
    65
    73
    66
        Eosinophils, Within, Above
    2
    1
    0
    3
        Eosinophils, Above, Within
    2
    3
    2
    4
        Eosinophils, Above, Above
    1
    2
    3
    4
        Erythrocytes, Below, Below
    1
    2
    1
    0
        Erythrocytes, Below, Within
    0
    1
    3
    0
        Erythrocytes, Within, Below
    1
    1
    1
    1
        Erythrocytes, Within, Within
    57
    45
    52
    53
        Erythrocytes, Within, Above
    4
    7
    7
    5
        Erythrocytes, Above, Within
    8
    5
    5
    5
        Erythrocytes, Above, Above
    8
    15
    13
    17
        Haematocrit, Below, Below
    4
    0
    0
    1
        Haematocrit, Below, Within
    1
    3
    2
    1
        Haematocrit, Within, Below
    2
    2
    2
    4
        Haematocrit, Within, Within
    62
    64
    73
    66
        Haematocrit, Within, Above
    0
    1
    1
    2
        Haematocrit, Above, Within
    9
    4
    2
    5
        Haematocrit, Above, Above
    1
    2
    2
    2
        Haemoglobin, Below, Below
    7
    3
    4
    3
        Haemoglobin, Below, Within
    5
    3
    4
    2
        Haemoglobin, Within, Below
    4
    9
    2
    5
        Haemoglobin, Within, Within
    58
    58
    68
    67
        Haemoglobin, Within, Above
    0
    1
    2
    0
        Haemoglobin, Above, Within
    4
    1
    0
    3
        Haemoglobin, Above, Above
    1
    1
    2
    1
        Lymphocytes, Below, Within
    0
    0
    0
    1
        Lymphocytes, Within, Within
    51
    54
    58
    51
        Lymphocytes, Within, Above
    2
    3
    6
    3
        Lymphocytes, Above, Within
    7
    9
    8
    14
        Lymphocytes, Above, Above
    19
    10
    10
    12
        Monocytes, Within, Below
    0
    0
    0
    1
        Monocytes, Within, Within
    50
    53
    51
    50
        Monocytes, Within, Above
    23
    16
    19
    18
        Monocytes, Above, Within
    2
    1
    4
    5
        Monocytes, Above, Above
    4
    6
    8
    7
        Neutrophils, Below, Below
    7
    4
    7
    7
        Neutrophils, Below, Within
    7
    6
    6
    6
        Neutrophils, Within, Below
    12
    16
    12
    11
        Neutrophils, Within, Within
    52
    49
    56
    56
        Neutrophils, Within, Above
    0
    1
    1
    0
        Neutrophils, Above, Within
    1
    0
    0
    1
        Platelets, Below, Above
    1
    0
    0
    0
        Platelets, Within, Within
    12
    19
    14
    18
        Platelets, Within, Above
    11
    14
    12
    6
        Platelets, Above, Within
    14
    10
    15
    16
        Platelets, Above, Above
    41
    33
    41
    41
        WBC, Below, Below
    2
    1
    1
    1
        WBC, Below, Within
    0
    4
    4
    2
        WBC, Within, Below
    4
    6
    5
    3
        WBC, Within, Within
    54
    51
    55
    60
        WBC, Within, Above
    2
    5
    3
    2
        WBC, Above, Within
    9
    6
    10
    7
        WBC, Above, Above
    8
    3
    4
    6
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention - Infants safety cohort [58] [59]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. 9999 = data not available. The analysis was performed on the Exposed Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    At Day 92
    Notes
    [58] - 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.
    [59] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        ALT, Below, Below
    0
    0
    1
    0
        ALT, Within, Within
    8
    8
    9
    28
        ALT, Above, Within
    1
    0
    0
    0
        AST, Within, Within
    8
    8
    9
    28
        AST, Within, Above
    0
    0
    1
    0
        AST, Above, Above
    1
    0
    0
    0
        Creatinine, Below, Below
    9
    8
    10
    28
        Potassium, Within, Within
    9999
    9999
    2
    6
        Potassium, Within, Above
    9999
    9999
    4
    3
        Potassium, Above, Within
    9999
    9999
    2
    0
        Potassium, Above, Above
    9999
    9999
    2
    1
        Sodium, Within, Within
    9999
    9999
    5
    9
        Sodium, Within, Above
    9999
    9999
    2
    1
        Sodium, Above, Within
    9999
    9999
    3
    0
        Urea, Below, Below
    9999
    9999
    7
    3
        Urea, Below, Within
    9999
    9999
    0
    3
        Urea, Within, Below
    9999
    9999
    1
    1
        Urea, Within, Within
    9999
    9999
    2
    3
        Basophils, Within, Within
    1
    3
    6
    12
        Basophils, Within, Above
    1
    3
    2
    5
        Basophils, Above, Within
    0
    1
    1
    1
        Basophils, Above, Above
    7
    1
    1
    10
        Eosinophils, Within, Below
    0
    0
    0
    1
        Eosinophils, Within, Within
    8
    6
    10
    24
        Eosinophils, Within, Above
    1
    0
    0
    1
        Eosinophils, Above, Within
    0
    1
    0
    1
        Eosinophils, Above, Above
    0
    1
    0
    1
        Erythrocytes, Below, Below
    0
    0
    0
    1
        Erythrocytes, Within, Below
    0
    0
    0
    1
        Erythrocytes, Within, Within
    6
    5
    7
    19
        Erythrocytes, Within, Above
    1
    1
    0
    1
        Erythrocytes, Above, Within
    0
    0
    1
    2
        Erythrocytes, Above, Above
    2
    2
    2
    4
        Haematocrit, Below, Below
    0
    0
    1
    0
        Haematocrit, Below, Within
    1
    0
    0
    0
        Haematocrit, Within, Below
    3
    0
    0
    1
        Haematocrit, Within, Within
    5
    5
    8
    21
        Haematocrit, Within, Above
    0
    0
    0
    3
        Haematocrit, Above, Within
    0
    3
    0
    2
        Haematocrit, Above, Above
    0
    0
    1
    1
        Haemoglobin, Below, Below
    4
    1
    2
    1
        Haemoglobin, Below, Within
    1
    0
    0
    0
        Haemoglobin, Within, Below
    0
    0
    0
    1
        Haemoglobin, Within, Within
    4
    7
    7
    26
        Haemoglobin, Above, Above
    0
    0
    1
    0
        Lymphocytes, Within, Within
    8
    5
    7
    14
        Lymphocytes, Within, Above
    0
    0
    1
    3
        Lymphocytes, Above, Within
    0
    1
    0
    1
        Lymphocytes, Above, Above
    1
    2
    2
    10
        Monocytes, Below, Within
    0
    0
    0
    1
        Monocytes, Within, Below
    0
    0
    1
    2
        Monocytes, Within, Within
    9
    6
    8
    24
        Monocytes, Within, Above
    0
    2
    1
    0
        Monocytes, Above, Above
    0
    0
    0
    1
        Neutrophils, Below, Below
    1
    0
    1
    1
        Neutrophils, Below, Within
    1
    1
    1
    2
        Neutrophils, Below, Above
    0
    1
    0
    0
        Neutrophils, Within, Below
    0
    1
    0
    2
        Neutrophils, Within, Within
    7
    5
    8
    22
        Neutrophils, Within, Above
    0
    0
    0
    1
        Platelets, Within, Within
    1
    2
    2
    7
        Platelets, Within, Above
    1
    0
    0
    2
        Platelets, Above, Within
    0
    0
    0
    4
        Platelets, Above, Above
    7
    6
    8
    15
        WBC, Below, Below
    0
    0
    1
    1
        WBC, Below, Within
    0
    0
    0
    1
        WBC, Within, Within
    8
    4
    6
    18
        WBC, Within, Above
    1
    3
    2
    2
        WBC, Above, Within
    0
    0
    0
    5
        WBC, Above, Above
    0
    1
    1
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after second study intervention - Infants dose-finding cohort [60] [61]
    End point description
    Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Infants, dose-finding cohort.
    End point type
    Primary
    End point timeframe
    At Day 92
    Notes
    [60] - 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.
    [61] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        ALT, Below, Below
    0
    1
    0
    0
        ALT, Below, Within
    0
    0
    1
    0
        ALT, Within, Below
    0
    0
    0
    2
        ALT, Within, Within
    70
    68
    71
    68
        ALT, Within, Above
    2
    2
    0
    3
        ALT, Above, Within
    0
    1
    2
    0
        AST, Within, Within
    69
    71
    73
    72
        AST, Within, Above
    2
    1
    0
    0
        AST, Above, Within
    1
    0
    0
    0
        AST, Above, Above
    0
    0
    1
    1
        Creatinine, Below, Below
    72
    71
    74
    72
        Creatinine, Below, Within
    0
    1
    0
    1
        Potassium, Within, Within
    18
    16
    18
    19
        Potassium, Within, Above
    24
    26
    34
    28
        Potassium, Above, Within
    9
    8
    2
    10
        Potassium, Above, Above
    21
    22
    20
    16
        Sodium, Within, Within
    48
    53
    54
    52
        Sodium, Within, Above
    7
    5
    8
    8
        Sodium, Above, Within
    17
    11
    10
    13
        Sodium, Above, Above
    0
    3
    2
    0
        Urea, Below, Below
    27
    24
    32
    24
        Urea, Below, Within
    9
    12
    7
    11
        Urea, Below, Above
    0
    1
    0
    0
        Urea, Within, Below
    13
    15
    13
    13
        Urea, Within, Within
    23
    20
    22
    25
        Basophils, Below, Within
    0
    1
    0
    0
        Basophils, Within, Below
    0
    0
    0
    2
        Basophils, Within, Within
    58
    58
    64
    54
        Basophils, Within, Above
    8
    3
    7
    8
        Basophils, Above, Within
    5
    5
    2
    5
        Basophils, Above, Above
    1
    5
    1
    4
        Eosinophils, Below, Within
    0
    0
    1
    0
        Eosinophils, Within, Below
    1
    2
    1
    1
        Eosinophils, Within, Within
    61
    60
    62
    61
        Eosinophils, Within, Above
    2
    1
    2
    4
        Eosinophils, Above, Within
    6
    0
    1
    2
        Eosinophils, Above, Above
    2
    9
    7
    5
        Erythrocytes, Below, Within
    1
    1
    0
    0
        Erythrocytes, Within, Below
    0
    0
    2
    0
        Erythrocytes, Within, Within
    48
    45
    44
    50
        Erythrocytes, Within, Above
    5
    2
    5
    3
        Erythrocytes, Above, Within
    5
    3
    4
    7
        Erythrocytes, Above, Above
    13
    21
    19
    13
        Haematocrit, Below, Below
    1
    0
    1
    2
        Haematocrit, Below, Within
    1
    2
    0
    0
        Haematocrit, Within, Below
    3
    2
    2
    3
        Haematocrit, Within, Within
    60
    60
    57
    62
        Haematocrit, Within, Above
    4
    0
    5
    1
        Haematocrit, Above, Within
    0
    5
    3
    2
        Haematocrit, Above, Above
    3
    3
    6
    3
        Haemoglobin, Below, Below
    7
    7
    5
    4
        Haemoglobin, Below, Within
    2
    3
    1
    1
        Haemoglobin, Within, Below
    5
    2
    4
    7
        Haemoglobin, Within, Within
    54
    56
    59
    57
        Haemoglobin, Within, Above
    1
    1
    1
    1
        Haemoglobin, Above, Within
    2
    2
    1
    2
        Haemoglobin, Above, Above
    1
    1
    3
    1
        Lymphocytes, Within, Below
    0
    0
    0
    1
        Lymphocytes, Within, Within
    38
    43
    44
    36
        Lymphocytes, Within, Above
    13
    11
    11
    9
        Lymphocytes, Above, Within
    6
    5
    10
    11
        Lymphocytes, Above, Above
    15
    13
    9
    16
        Monocytes, Below, Within
    1
    0
    0
    0
        Monocytes, Within, Below
    0
    0
    0
    2
        Monocytes, Within, Within
    52
    47
    60
    62
        Monocytes, Within, Above
    7
    15
    8
    2
        Monocytes, Above, Within
    9
    7
    3
    4
        Monocytes, Above, Above
    3
    3
    3
    3
        Neutrophils, Below, Below
    1
    1
    3
    5
        Neutrophils, Below, Within
    6
    7
    11
    6
        Neutrophils, Within, Below
    5
    7
    3
    2
        Neutrophils, Within, Within
    57
    53
    54
    60
        Neutrophils, Within, Above
    2
    2
    1
    0
        Neutrophils, Above, Within
    1
    2
    1
    0
        Neutrophils, Above, Above
    0
    0
    1
    0
        Platelets, Within, Within
    9
    15
    11
    15
        Platelets, Within, Above
    10
    14
    16
    5
        Platelets, Above, Below
    1
    0
    0
    0
        Platelets, Above, Within
    8
    6
    7
    7
        Platelets, Above, Above
    44
    37
    40
    46
        WBC, Below, Within
    3
    1
    2
    2
        WBC, Within, Below
    3
    1
    1
    3
        WBC, Within, Within
    47
    48
    56
    53
        WBC, Within, Above
    6
    9
    5
    7
        WBC, Above, Within
    5
    6
    3
    2
        WBC, Above, Above
    8
    7
    7
    6
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after third study intervention - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after third study intervention - Infants safety cohort [62] [63]
    End point description
    Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Infants, safety cohort.
    End point type
    Primary
    End point timeframe
    At Day 260
    Notes
    [62] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    [63] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        ALT, Within, Within
    9
    8
    9
    27
        ALT, Above, Above
    0
    0
    0
    1
        AST, Within, Within
    9
    8
    9
    28
        Creatinine, Below, Below
    8
    8
    9
    28
        Creatinine, Within, Below
    1
    0
    0
    0
        Potassium, Within, Within
    1
    3
    3
    11
        Potassium, Within, Above
    3
    1
    0
    5
        Potassium, Above, Within
    1
    1
    3
    7
        Potassium, Above, Above
    4
    3
    3
    5
        Sodium, Within, Within
    4
    8
    6
    18
        Sodium, Within, Above
    2
    0
    0
    2
        Sodium, Above, Within
    1
    0
    3
    5
        Sodium, Above, Above
    2
    0
    0
    3
        Urea, Below, Below
    3
    2
    5
    9
        Urea, Below, Within
    3
    1
    1
    2
        Urea, Within, Below
    1
    1
    1
    4
        Urea, Within, Within
    2
    4
    2
    13
        Basophils, Within, Within
    5
    7
    8
    23
        Basophils, Within, Above
    2
    0
    0
    3
        Basophils, Above, Within
    2
    0
    1
    2
        Basophils, Above, Above
    0
    1
    0
    0
        Eosinophils, Below, Within
    0
    0
    0
    2
        Eosinophils, Within, Within
    8
    7
    9
    22
        Eosinophils, Within, Above
    1
    0
    0
    1
        Eosinophils, Above, Above
    0
    1
    0
    3
        Erythrocytes, Below, Below
    0
    0
    0
    1
        Erythrocytes, Within, Within
    6
    4
    7
    20
        Erythrocytes, Within, Above
    1
    1
    0
    0
        Erythrocytes, Above, Within
    1
    2
    2
    3
        Erythrocytes, Above, Above
    1
    1
    0
    4
        Haematocrit, Below, Below
    0
    0
    0
    2
        Haematocrit, Below, Within
    0
    0
    0
    1
        Haematocrit, Within, Within
    7
    6
    8
    16
        Haematocrit, Within, Above
    1
    1
    0
    2
        Haematocrit, Above, Within
    1
    1
    0
    2
        Haematocrit, Above, Above
    0
    0
    1
    5
        Haemoglobin, Below, Below
    0
    0
    2
    3
        Haemoglobin, Below, Within
    0
    0
    0
    2
        Haemoglobin, Within, Below
    1
    0
    0
    1
        Haemoglobin, Within, Within
    8
    8
    6
    17
        Haemoglobin, Within, Above
    0
    0
    0
    2
        Haemoglobin, Above, Within
    0
    0
    0
    2
        Haemoglobin, Above, Above
    0
    0
    1
    1
        Lymphocytes, Within, Within
    6
    6
    6
    21
        Lymphocytes, Within, Above
    2
    1
    0
    2
        Lymphocytes, Above, Within
    1
    1
    1
    2
        Lymphocytes, Above, Above
    0
    0
    2
    3
        Monocytes, Below, Within
    1
    0
    0
    2
        Monocytes, Within, Below
    0
    0
    1
    0
        Monocytes, Within, Within
    7
    8
    6
    22
        Monocytes, Within, Above
    1
    0
    2
    2
        Monocytes, Above, Within
    0
    0
    0
    1
        Monocytes, Above, Above
    0
    0
    0
    1
        Neutrophils, Below, Below
    0
    0
    0
    1
        Neutrophils, Below, Within
    0
    1
    2
    1
        Neutrophils, Within, Below
    1
    0
    1
    2
        Neutrophils, Within, Within
    8
    5
    6
    24
        Neutrophils, Within, Above
    0
    2
    0
    0
        Platelets, Below, Within
    0
    1
    0
    0
        Platelets, Within, Within
    2
    2
    2
    6
        Platelets, Within, Above
    0
    0
    3
    5
        Platelets, Above, Within
    2
    1
    2
    5
        Platelets, Above, Above
    5
    4
    2
    12
        WBC, Below, Below
    0
    0
    1
    0
        WBC, Below, Within
    1
    2
    2
    0
        WBC, Within, Below
    0
    0
    0
    3
        WBC, Within, Within
    7
    4
    3
    18
        WBC, Within, Above
    1
    1
    2
    3
        WBC, Above, Within
    0
    1
    0
    3
        WBC, Above, Above
    0
    0
    1
    1
    No statistical analyses for this end point

    Primary: Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after third study intervention - Infants dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results after third study intervention - Infants dose-finding cohort [64] [65]
    End point description
    Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. The analysis was performed on the Exposed Set for Stage 2 Infants, dose-finding cohort.
    End point type
    Primary
    End point timeframe
    At Day 260
    Notes
    [64] - 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.
    [65] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        ALT, Below, Within
    1
    2
    1
    2
        ALT, Within, Below
    2
    1
    0
    0
        ALT, Within, Within
    64
    67
    69
    65
        ALT, Within, Above
    1
    0
    3
    0
        ALT, Above, Within
    1
    1
    0
    0
        ALT, Above, Above
    0
    0
    0
    4
        AST, Within, Within
    68
    71
    71
    70
        AST, Within, Above
    1
    0
    1
    0
        AST, Above, Within
    0
    0
    1
    0
        AST, Above, Above
    0
    0
    0
    1
        Creatinine, Below, Below
    68
    70
    73
    71
        Creatinine, Below, Within
    0
    1
    0
    0
        Creatinine, Within, Below
    1
    0
    0
    0
        Potassium, Within, Within
    26
    28
    25
    21
        Potassium, Within, Above
    12
    18
    23
    23
        Potassium, Above, Within
    11
    8
    7
    10
        Potassium, Above, Above
    20
    17
    18
    17
        Sodium, Below, Within
    1
    2
    4
    2
        Sodium, Within, Below
    0
    0
    1
    0
        Sodium, Within, Within
    55
    61
    55
    63
        Sodium, Within, Above
    4
    4
    7
    2
        Sodium, Above, Within
    8
    3
    6
    4
        Sodium, Above, Above
    1
    1
    0
    0
        Urea, Below, Below
    18
    15
    16
    13
        Urea, Below, Within
    12
    6
    11
    12
        Urea, Within, Below
    10
    14
    14
    5
        Urea, Within, Within
    29
    36
    32
    41
        Basophils, Below, Within
    0
    0
    0
    1
        Basophils, Within, Within
    53
    54
    62
    53
        Basophils, Within, Above
    7
    8
    4
    8
        Basophils, Above, Within
    6
    6
    6
    3
        Basophils, Above, Above
    3
    3
    1
    6
        Eosinophils, Below, Within
    1
    1
    0
    3
        Eosinophils, Within, Below
    0
    2
    2
    0
        Eosinophils, Within, Within
    59
    58
    59
    56
        Eosinophils, Within, Above
    2
    4
    2
    2
        Eosinophils, Above, Within
    2
    1
    3
    3
        Eosinophils, Above, Above
    5
    5
    7
    7
        Erythrocytes, Below, Below
    0
    1
    0
    0
        Erythrocytes, Within, Within
    44
    39
    46
    44
        Erythrocytes, Within, Above
    4
    5
    5
    5
        Erythrocytes, Above, Within
    8
    2
    4
    5
        Erythrocytes, Above, Above
    13
    24
    18
    17
        Haematocrit, Below, Below
    2
    2
    0
    0
        Haematocrit, Below, Within
    1
    1
    0
    1
        Haematocrit, Within, Below
    0
    1
    0
    0
        Haematocrit, Within, Within
    55
    55
    56
    57
        Haematocrit, Within, Above
    1
    7
    9
    1
        Haematocrit, Above, Within
    5
    2
    2
    7
        Haematocrit, Above, Above
    5
    3
    6
    5
        Haemoglobin, Below, Below
    6
    4
    4
    4
        Haemoglobin, Below, Within
    3
    3
    0
    3
        Haemoglobin, Within, Below
    2
    5
    2
    1
        Haemoglobin, Within, Within
    53
    52
    57
    59
        Haemoglobin, Within, Above
    1
    2
    4
    1
        Haemoglobin, Above, Within
    2
    1
    4
    2
        Haemoglobin, Above, Above
    2
    4
    2
    1
        Lymphocytes, Within, Within
    43
    57
    58
    48
        Lymphocytes, Within, Above
    13
    6
    5
    8
        Lymphocytes, Above, Within
    4
    3
    8
    8
        Lymphocytes, Above, Above
    9
    5
    2
    7
        Monocytes, Below, Below
    1
    0
    0
    0
        Monocytes, Below, Within
    1
    0
    2
    1
        Monocytes, Within, Below
    1
    1
    0
    2
        Monocytes, Within, Within
    54
    61
    63
    62
        Monocytes, Within, Above
    7
    3
    5
    3
        Monocytes, Above, Within
    4
    4
    2
    2
        Monocytes, Above, Above
    1
    2
    1
    1
        Neutrophils, Below, Below
    5
    1
    0
    1
        Neutrophils, Below, Within
    4
    5
    9
    6
        Neutrophils, Within, Below
    3
    3
    5
    5
        Neutrophils, Within, Within
    55
    60
    58
    58
        Neutrophils, Within, Above
    1
    0
    0
    1
        Neutrophils, Above, Within
    1
    2
    1
    0
        Platelets, Below, Below
    0
    0
    1
    0
        Platelets, Below, Within
    0
    0
    1
    0
        Platelets, Within, Within
    17
    21
    19
    16
        Platelets, Within, Above
    10
    18
    17
    11
        Platelets, Above, Within
    8
    7
    8
    6
        Platelets, Above, Above
    34
    25
    27
    38
        WBC, Below, Below
    1
    0
    2
    0
        WBC, Below, Within
    4
    3
    6
    2
        WBC, Within, Below
    1
    2
    1
    0
        WBC, Within, Within
    44
    51
    53
    53
        WBC, Within, Above
    6
    6
    2
    6
        WBC, Above, Within
    4
    7
    6
    6
        WBC, Above, Above
    9
    2
    3
    4
    No statistical analyses for this end point

    Secondary: Stage 1: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 18 to 50 years of age in Europe

    		 Close Top of page
    End point title
    		 Stage 1: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 18 to 50 years of age in Europe [66]
    End point description
    Anti-serotype specific Shigella LPS/OAg serum IgG GMCs were measured by ELISA and expressed in EU/mL of serum. S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes were tested. 9999 = data not available. The analysis was performed on the PPS for Stage 1 Adults. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85/Day 169(before each study intervention); at Day 15 (14 days after the first study intervention); at Day 29 and Day 113/Day 197 (28 days after each study intervention)
    Notes
    [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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: EU/mL
    geometric mean (confidence interval 95%)
        S sonnei Ab IgG, Day 1
    15.3 (10.8 to 21.8)
    8.9 (6.9 to 11.5)
    21.0 (13.2 to 33.6)
        S sonnei Ab IgG, Day 15
    307.5 (167.3 to 565.2)
    170.7 (98.2 to 296.5)
    18.4 (11.6 to 29.3)
        S sonnei Ab IgG, Day 29
    325.3 (181.6 to 582.8)
    172.1 (96.7 to 306.4)
    18.1 (11.5 to 28.6)
        S sonnei Ab IgG, Day 85
    287.6 (144.1 to 574.1)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S sonnei Ab IgG, Day 169
    9999 (9999 to 9999)
    94.8 (55.2 to 162.9)
    9999 (9999 to 9999)
        S sonnei Ab IgG, Day 85/169
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    19.0 (11.1 to 32.3)
        S sonnei Ab IgG, Day 113
    387.8 (206.6 to 727.8)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S sonnei Ab IgG, Day 197
    9999 (9999 to 9999)
    167.2 (104.3 to 267.9)
    9999 (9999 to 9999)
        S sonnei Ab IgG, Day 113/197
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    19.9 (11.8 to 33.7)
        S flexneri 1b Ab IgG, Day 1
    23.5 (13.6 to 40.5)
    22.9 (13.9 to 37.8)
    26.9 (15.3 to 47.3)
        S flexneri 1b Ab IgG, Day 15
    123.1 (71.8 to 211.1)
    102.1 (63.8 to 163.5)
    27.4 (16.1 to 46.7)
        S flexneri 1b Ab IgG, Day 29
    118.3 (70.5 to 198.5)
    90.2 (55.9 to 145.5)
    27.0 (15.8 to 46.3)
        S flexneri 1b Ab IgG, Day 85
    79.1 (45.3 to 138.1)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S flexneri 1b Ab IgG, Day 169
    9999 (9999 to 9999)
    48.5 (30.1 to 78.0)
    9999 (9999 to 9999)
        S flexneri 1b Ab IgG, Day 85/169
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    27.2 (15.5 to 47.7)
        S flexneri 1b Ab IgG, Day 113
    129.7 (79.6 to 211.5)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S flexneri 1b Ab IgG, Day 197
    9999 (9999 to 9999)
    73.0 (48.6 to 109.7)
    9999 (9999 to 9999)
        S flexneri 1b Ab IgG, Day 113/197
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    26.1 (14.6 to 46.9)
        S flexneri 2a Ab IgG, Day 1
    33.3 (23.1 to 47.9)
    32.7 (22.2 to 48.2)
    44.5 (27.3 to 72.6)
        S flexneri 2a Ab IgG, Day 15
    608.0 (432.4 to 854.9)
    635.2 (459.5 to 878.1)
    44.3 (27.4 to 71.6)
        S flexneri 2a Ab IgG, Day 29
    545.8 (393.1 to 757.6)
    582.6 (424.1 to 800.4)
    42.8 (26.3 to 69.5)
        S flexneri 2a Ab IgG, Day 85
    411.8 (300.4 to 564.6)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S flexneri 2a Ab IgG, Day 169
    9999 (9999 to 9999)
    364.9 (259.9 to 512.5)
    9999 (9999 to 9999)
        S flexneri 2a Ab IgG, Day 85/169
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    41.4 (23.3 to 73.6)
        S flexneri 2a Ab IgG, Day 113
    473.6 (351.1 to 638.8)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S flexneri 2a Ab IgG, Day 197
    9999 (9999 to 9999)
    451.0 (327.8 to 620.6)
    9999 (9999 to 9999)
        S flexneri 2a Ab IgG, Day 113/197
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    43.8 (25.1 to 76.3)
        S flexneri 3a Ab IgG, Day 1
    17.3 (11.1 to 27.0)
    14.2 (8.4 to 23.9)
    19.9 (13.1 to 30.2)
        S flexneri 3a Ab IgG, Day 15
    59.1 (40.5 to 86.1)
    63.8 (36.2 to 112.4)
    18.4 (12.2 to 27.8)
        S flexneri 3a Ab IgG, Day 29
    56.7 (37.6 to 85.4)
    60.6 (34.8 to 105.5)
    19.3 (12.7 to 29.4)
        S flexneri 3a Ab IgG, Day 85
    26.9 (16.7 to 43.4)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S flexneri 3a Ab IgG, Day 169
    9999 (9999 to 9999)
    24.7 (14.1 to 43.2)
    9999 (9999 to 9999)
        S flexneri 3a Ab IgG, Day 85/169
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    10.1 (6.4 to 15.9)
        S flexneri 3a Ab IgG, Day 113
    43.1 (26.9 to 69.2)
    9999 (9999 to 9999)
    9999 (9999 to 9999)
        S flexneri 3a Ab IgG, Day 197
    9999 (9999 to 9999)
    37.2 (22.4 to 61.7)
    9999 (9999 to 9999)
        S flexneri 3a Ab IgG, Day 113/197
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    9.2 (5.6 to 15.0)
    No statistical analyses for this end point

    Secondary: Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 18 to 50 years of age in Africa

    		 Close Top of page
    End point title
    		 Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 18 to 50 years of age in Africa [67]
    End point description
    The analysis was performed on the PPS for Stage 2 Adults.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85 (before each study intervention administration) and Day 29 and Day 113 (28 days after each study intervention administration)
    Notes
    [67] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: EU/mL
    geometric mean (confidence interval 95%)
        S sonnei Ab IgG, Day 1
    166.4 (82.8 to 334.2)
    171.2 (65.0 to 450.6)
        S sonnei Ab IgG, Day 29
    3112.0 (2181.6 to 4439.2)
    172.0 (66.7 to 443.6)
        S sonnei Ab IgG, Day 85
    2046.5 (1372.1 to 3052.5)
    182.1 (73.2 to 453.1)
        S sonnei Ab IgG, Day 113
    1974.4 (1288.5 to 3025.6)
    172.3 (68.8 to 431.6)
        S flexneri 1b Ab IgG, Day 1
    194.7 (44.0 to 862.2)
    106.4 (41.0 to 276.2)
        S flexneri 1b Ab IgG, Day 29
    388.5 (98.6 to 1531.3)
    103.3 (40.2 to 265.8)
        S flexneri 1b Ab IgG, Day 85
    328.0 (84.8 to 1268.8)
    110.8 (38.9 to 315.5)
        S flexneri 1b Ab IgG, Day 113
    358.3 (98.6 to 1301.7)
    107.2 (37.5 to 306.1)
        S flexneri 2a Ab IgG, Day 1
    192.3 (93.7 to 394.6)
    155.8 (70.7 to 343.6)
        S flexneri 2a Ab IgG, Day 29
    563.0 (269.1 to 1177.7)
    146.1 (68.7 to 311.0)
        S flexneri 2a Ab IgG, Day 85
    463.0 (220.3 to 973.4)
    158.1 (67.7 to 369.3)
        S flexneri 2a Ab IgG, Day 113
    538.6 (269.9 to 1074.7)
    154.0 (68.5 to 346.2)
        S flexneri 3a Ab IgG, Day 1
    84.8 (34.5 to 208.8)
    61.3 (19.6 to 192.0)
        S flexneri 3a Ab IgG, Day 29
    212.8 (89.9 to 503.6)
    57.4 (18.2 to 181.5)
        S flexneri 3a Ab IgG, Day 85
    174.4 (75.1 to 405.3)
    62.3 (16.7 to 233.3)
        S flexneri 3a Ab IgG, Day 113
    225.4 (103.2 to 492.7)
    61.6 (16.7 to 226.8)
    No statistical analyses for this end point

    Secondary: Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 24 to 59 months of age in Africa

    		 Close Top of page
    End point title
    		 Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 24 to 59 months of age in Africa [68]
    End point description
    The analysis was performed on the PPS for Stage 2 Children.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85 (before each study intervention) and Day 29 and Day 113 (28 days after each study intervention)
    Notes
    [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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: EU/mL
    geometric mean (confidence interval 95%)
        S sonnei Ab IgG, Day 1
    22.7 (8.5 to 61.0)
    39.1 (9.5 to 160.1)
    20.7 (10.5 to 41.0)
        S sonnei Ab IgG, Day 29
    899.0 (122.7 to 6588.6)
    746.9 (93.9 to 5940.9)
    19.3 (10.4 to 35.8)
        S sonnei Ab IgG, Day 85)
    702.7 (125.7 to 3927.4)
    388.2 (56.6 to 2663.4)
    24.7 (11.1 to 54.7)
        S sonnei Ab IgG, Day 113
    1163.2 (289.8 to 4668.7)
    560.2 (86.0 to 3651.0)
    40.2 (15.9 to 101.6)
        S flexneri 1b Ab IgG, Day 1
    28.6 (6.6 to 123.1)
    38.4 (7.0 to 211.4)
    37.0 (16.4 to 83.3)
        S flexneri 1b Ab IgG, Day 29
    74.0 (23.3 to 234.8)
    119.4 (27.2 to 525.1)
    33.4 (13.6 to 81.7)
        S flexneri 1b Ab IgG, Day 85
    39.3 (10.7 to 144.5)
    65.4 (13.1 to 326.7)
    34.5 (15.0 to 79.6)
        S flexneri 1b Ab IgG, Day 113
    66.7 (20.5 to 217.0)
    100.3 (21.6 to 466.4)
    31.9 (14.0 to 72.4)
        S flexneri 2a Ab IgG, Day 1
    24.5 (5.1 to 117.9)
    21.0 (4.7 to 93.0)
    30.9 (12.4 to 77.3)
        S flexneri 2a Ab IgG, Day 29
    219.2 (65.6 to 732.9)
    193.5 (76.2 to 491.6)
    30.6 (12.7 to 74.2)
        S flexneri 2a Ab IgG, Day 85
    101.2 (28.7 to 356.9)
    103.8 (36.3 to 297.0)
    32.1 (14.2 to 72.5)
        S flexneri 2a Ab IgG, Day 113
    267.3 (101.0 to 707.4)
    290.0 (115.0 to 731.3)
    29.5 (13.8 to 63.2)
        S flexneri 3a Ab IgG, Day 1
    14.2 (4.5 to 44.7)
    8.5 (3.5 to 20.6)
    7.6 (3.0 to 19.8)
        S flexneri 3a Ab IgG, Day 29
    30.7 (10.7 to 87.9)
    22.0 (7.6 to 63.7)
    6.2 (2.5 to 15.2)
        S flexneri 3a Ab IgG, Day 85
    17.8 (5.9 to 53.4)
    14.1 (4.9 to 40.3)
    6.2 (2.7 to 14.2)
        S flexneri 3a Ab IgG, Day 113
    32.1 (12.3 to 84.2)
    26.1 (10.2 to 66.7)
    7.0 (3.2 to 15.6)
    No statistical analyses for this end point

    Secondary: Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 9 months of age in Africa - Infants safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 9 months of age in Africa - Infants safety cohort [69]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, safety cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1, Day 85 and Day 253 (before each study intervention administration) and Day 29, Day 113 and Day 281 (28 days after each study intervention administration)
    Notes
    [69] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: EU/mL
    geometric mean (confidence interval 95%)
        S sonnei Ab IgG, Day 1
    6.4 (6.4 to 6.4)
    6.9 (5.8 to 8.1)
    6.4 (6.4 to 6.4)
    6.6 (6.2 to 6.9)
        S sonnei Ab IgG, Day 29
    16.9 (7.8 to 36.6)
    17.5 (9.5 to 32.4)
    17.3 (9.1 to 33.0)
    6.4 (6.4 to 6.4)
        S sonnei Ab IgG, Day 85
    27.2 (12.6 to 58.3)
    32.7 (16.1 to 66.6)
    23.3 (11.1 to 48.9)
    6.4 (6.4 to 6.4)
        S sonnei Ab IgG, Day 113
    240.4 (60.3 to 958.3)
    264.7 (105.1 to 666.9)
    171.0 (67.7 to 431.6)
    6.4 (6.4 to 6.4)
        S sonnei Ab IgG, Day 253
    128.5 (60.1 to 274.9)
    99.5 (50.4 to 196.3)
    63.4 (24.4 to 165.1)
    6.4 (6.4 to 6.4)
        S sonnei Ab IgG, Day 281
    429.9 (155.7 to 1186.8)
    275.8 (90.1 to 844.3)
    185.2 (111.2 to 308.4)
    6.4 (6.4 to 6.4)
        S flexneri 1b Ab IgG, Day 1
    6.0 (2.5 to 14.8)
    6.4 (3.9 to 10.6)
    4.2 (2.4 to 7.4)
    5.9 (4.1 to 8.5)
        S flexneri 1b Ab IgG, Day 29
    24.2 (8.2 to 71.2)
    18.5 (10.6 to 32.3)
    7.0 (3.1 to 16.0)
    6.3 (4.6 to 8.6)
        S flexneri 1b Ab IgG, Day 85
    16.3 (6.7 to 40.0)
    9.4 (4.9 to 17.8)
    6.3 (3.1 to 12.7)
    7.4 (5.0 to 10.9)
        S flexneri 1b Ab IgG, Day 113
    30.5 (8.6 to 108.0)
    18.2 (12.1 to 27.5)
    14.2 (5.0 to 40.2)
    7.4 (5.0 to 10.9)
        S flexneri 1b Ab IgG, Day 253
    9.0 (3.5 to 23.2)
    7.2 (3.2 to 16.1)
    8.9 (4.5 to 17.3)
    7.4 (5.0 to 10.9)
        S flexneri 1b Ab IgG, Day 281
    23.3 (9.5 to 57.0)
    20.4 (8.1 to 51.2)
    29.4 (15.3 to 56.6)
    8.0 (5.3 to 12.0)
        S flexneri 2a Ab IgG, Day 1
    3.6 (1.5 to 9.0)
    4.4 (2.3 to 8.3)
    3.9 (1.8 to 8.4)
    4.1 (2.2 to 7.4)
        S flexneri 2a Ab IgG, Day 29
    34.6 (11.0 to 109.1)
    40.5 (16.3 to 100.6)
    17.1 (6.0 to 49.0)
    4.6 (2.5 to 8.4)
        S flexneri 2a Ab IgG, Day 85
    29.6 (11.5 to 76.6)
    16.4 (7.4 to 36.3)
    9.7 (3.8 to 24.7)
    5.8 (3.2 to 10.6)
        S flexneri 2a Ab IgG, Day 113
    81.6 (38.9 to 171.1)
    77.4 (31.1 to 192.5)
    65.5 (33.0 to 130.0)
    7.2 (3.6 to 14.2)
        S flexneri 2a Ab IgG, Day 253
    9.9 (2.5 to 38.8)
    11.2 (2.7 to 47.6)
    14.4 (5.2 to 40.1)
    7.7 (3.9 to 15.2)
        S flexneri 2a Ab IgG, Day 281
    135.0 (81.6 to 223.1)
    72.5 (24.6 to 213.7)
    110.7 (60.4 to 203.0)
    8.2 (4.4 to 15.2)
        S flexneri 3a Ab IgG, Day 1
    2.7 (1.3 to 5.6)
    5.1 (2.7 to 9.7)
    2.6 (1.4 to 4.7)
    3.3 (2.2 to 5.0)
        S flexneri 3a Ab IgG, Day 29
    9.6 (3.4 to 26.9)
    8.9 (3.1 to 25.2)
    3.5 (1.7 to 7.3)
    3.4 (2.2 to 5.2)
        S flexneri 3a Ab IgG, Day 85
    5.1 (2.2 to 12.2)
    6.0 (2.4 to 15.1)
    2.1 (1.1 to 4.2)
    4.0 (2.5 to 6.4)
        S flexneri 3a Ab IgG, Day 113
    12.5 (4.0 to 38.4)
    7.9 (2.5 to 25.1)
    4.5 (2.3 to 8.8)
    3.8 (2.4 to 5.8)
        S flexneri 3a Ab IgG, Day 253
    6.8 (2.4 to 19.2)
    8.5 (2.0 to 35.6)
    3.2 (1.6 to 6.5)
    4.5 (2.8 to 7.0)
        S flexneri 3a Ab IgG, Day 281
    23.0 (7.0 to 75.8)
    20.4 (5.2 to 79.7)
    13.2 (3.5 to 49.8)
    4.9 (3.1 to 7.9)
    No statistical analyses for this end point

    Secondary: Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 9 months of age in Africa - dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in participants 9 months of age in Africa - dose-finding cohort [70]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1, Day 85 and Day 253 (before each study intervention administration) and Day 29, Day 113 and Day 281 (28 days after each study intervention administration)
    Notes
    [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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: EU/mL
    geometric mean (confidence interval 95%)
        S sonnei Ab IgG, Day 1
    10.9 (8.9 to 13.2)
    9.5 (8.1 to 11.0)
    10.7 (8.7 to 13.3)
    9.8 (8.2 to 11.6)
        S sonnei Ab IgG, Day 29
    36.0 (27.4 to 47.4)
    41.9 (33.6 to 52.4)
    38.5 (29.0 to 51.3)
    9.5 (8.1 to 11.1)
        S sonnei Ab IgG, Day 85
    41.7 (32.3 to 53.9)
    46.7 (36.8 to 59.2)
    41.1 (33.5 to 50.6)
    8.2 (6.9 to 9.7)
        S sonnei Ab IgG, Day 113
    313.6 (224.5 to 438.1)
    353.4 (244.7 to 510.4)
    328.7 (235.4 to 459.1)
    9.0 (7.2 to 11.3)
        S sonnei Ab IgG, Day 253
    162.1 (128.9 to 203.8)
    195.3 (154.9 to 246.2)
    219.0 (164.3 to 291.8)
    16.9 (12.5 to 22.8)
        S sonnei Ab IgG, Day 281
    446.3 (342.1 to 582.3)
    535.1 (416.2 to 688.0)
    603.8 (461.4 to 790.2)
    18.6 (13.7 to 25.2)
        S flexneri 1b Ab IgG, Day 1
    11.4 (8.5 to 15.4)
    11.8 (8.7 to 15.9)
    12.6 (9.1 to 17.3)
    13.4 (9.9 to 18.0)
        S flexneri 1b Ab IgG, Day 29
    32.9 (23.7 to 45.6)
    47.5 (34.8 to 64.9)
    36.8 (26.5 to 51.0)
    13.4 (10.0 to 18.0)
        S flexneri 1b Ab IgG, Day 85
    13.0 (9.9 to 17.0)
    11.1 (8.5 to 14.4)
    9.6 (7.5 to 12.3)
    8.1 (6.2 to 10.7)
        S flexneri 1b Ab IgG, Day 113
    25.4 (18.5 to 34.8)
    21.2 (17.4 to 25.8)
    20.6 (16.4 to 25.8)
    7.4 (5.7 to 9.5)
        S flexneri 1b Ab IgG, Day 253
    15.7 (11.6 to 21.3)
    9.3 (7.4 to 11.7)
    10.3 (7.8 to 13.5)
    16.9 (11.7 to 24.2)
        S flexneri 1b Ab IgG, Day 281
    57.3 (43.2 to 76.0)
    34.4 (26.6 to 44.3)
    36.7 (28.1 to 47.9)
    16.6 (11.5 to 23.9)
        S flexneri 2a Ab IgG, Day 1
    6.1 (4.6 to 8.2)
    5.2 (4.0 to 6.6)
    6.2 (4.7 to 8.2)
    5.7 (4.4 to 7.5)
        S flexneri 2a Ab IgG, Day 29
    51.6 (38.1 to 69.9)
    58.2 (42.6 to 79.5)
    59.4 (42.2 to 83.7)
    6.2 (4.7 to 8.2)
        S flexneri 2a Ab IgG, Day 85
    20.0 (14.0 to 28.6)
    12.7 (9.2 to 17.7)
    14.4 (10.1 to 20.6)
    4.7 (3.2 to 6.7)
        S flexneri 2a Ab IgG, Day 113
    95.4 (72.4 to 125.5)
    69.9 (52.2 to 93.7)
    84.4 (62.4 to 114.2)
    4.5 (3.2 to 6.4)
        S flexneri 2a Ab IgG, Day 253
    27.5 (19.9 to 38.1)
    19.5 (15.3 to 25.0)
    23.2 (18.0 to 30.0)
    11.8 (8.2 to 17.1)
        S flexneri 2a Ab IgG, Day 281
    189.2 (139.2 to 257.2)
    142.3 (112.6 to 179.7)
    177.9 (134.7 to 234.9)
    12.1 (8.3 to 17.4)
        S flexneri 3a Ab IgG, Day 1
    8.1 (5.3 to 12.5)
    5.4 (3.7 to 7.9)
    6.3 (4.1 to 9.6)
    10.2 (6.6 to 15.8)
        S flexneri 3a Ab IgG, Day 29
    22.4 (15.2 to 33.0)
    19.1 (12.8 to 28.5)
    14.8 (9.7 to 22.6)
    10.0 (6.3 to 15.8)
        S flexneri 3a Ab IgG, Day 85
    11.1 (7.3 to 16.6)
    11.4 (7.7 to 16.8)
    6.6 (4.5 to 9.8)
    8.5 (5.5 to 13.2)
        S flexneri 3a Ab IgG, Day 113
    25.7 (17.3 to 38.3)
    18.4 (12.2 to 27.7)
    16.0 (11.2 to 22.9)
    7.7 (5.2 to 11.5)
        S flexneri 3a Ab IgG, Day 253
    13.5 (9.8 to 18.7)
    8.8 (6.6 to 11.8)
    9.6 (6.9 to 13.2)
    10.7 (7.4 to 15.5)
        S flexneri 3a Ab IgG, Day 281
    45.7 (34.0 to 61.5)
    28.1 (21.1 to 37.4)
    36.3 (27.0 to 48.8)
    10.9 (7.4 to 16.1)
    No statistical analyses for this end point

    Secondary: Stage 1: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg [71]
    End point description
    The analysis was performed on the PPS for Stage 1 Adults. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group. 9999 = data not available.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85/Day 169 (before each study intervention); at Day 15 (14 days after the first study intervention); at Day 29 and Day 113/Day 197 (28 days after each study intervention)
    Notes
    [71] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        Day 1
    1
    0
    5
        Day 15
    22
    19
    4
        Day 29
    22
    18
    4
        Day 85
    17
    9999
    9999
        Day 169
    9999
    14
    9999
        Day 85/169
    9999
    9999
    3
        Day 113
    21
    9999
    9999
        Day 197
    9999
    22
    9999
        Day 113/197
    9999
    9999
    3
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg [72]
    End point description
    The analysis was performed on the PPS for Stage 2 Adults.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85 (before each study intervention) and Day 29 and Day 113 (28 days after each study intervention)
    Notes
    [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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        Day 1
    7
    5
        Day 29
    10
    5
        Day 85
    10
    6
        Day 113
    10
    5
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 24 to 59 months of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg [73]
    End point description
    The analysis was performed on the PPS for Stage 2 Children.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85 (before each study intervention) and Day 29 and Day 113 (28 days after each study intervention)
    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 analysis of this primary endpoint was descriptive i.e. no statistical hypothesis test was performed.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        Day 1
    2
    4
    3
        Day 29
    7
    6
    2
        Day 85
    7
    6
    3
        Day 113
    7
    6
    5
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/Oag - safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/Oag - safety cohort [74]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, safety cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
    Notes
    [74] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        Day 1
    0
    0
    0
    0
        Day 29
    0
    0
    0
    0
        Day 85
    0
    1
    0
    0
        Day 113
    6
    6
    5
    0
        Day 253
    4
    2
    3
    0
        Day 281
    6
    6
    6
    0
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/Oag - dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/Oag - dose-finding cohort [75]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
    Notes
    [75] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        Day 1
    1
    0
    2
    1
        Day 29
    10
    11
    12
    0
        Day 85
    9
    9
    6
    1
        Day 113
    51
    52
    57
    2
        Day 253
    42
    48
    49
    8
        Day 281
    61
    61
    67
    8
    No statistical analyses for this end point

    Secondary: Stage 1: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg [76]
    End point description
    The analysis was performed on the PPS for Stage 1 Adults. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group. 9999 = data not available.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85/Day 169 (before each study intervention); at Day 15 (14 days after the first study intervention); at Day 29 and Day 113/Day 197 (28 days after each study intervention)
    Notes
    [76] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    34
    Units: Participants
        Day 1
    1
    0
    2
        Day 15
    13
    11
    2
        Day 29
    12
    11
    2
        Day 85
    12
    9999
    9999
        Day 169
    9999
    9
    9999
        Day 85/169
    9999
    9999
    2
        Day 113
    11
    9999
    9999
        Day 197
    9999
    10
    9999
        Day 113/197
    9999
    9999
    2
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg [77]
    End point description
    The analysis was performed on the PPS for Stage 2 Adults.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85 (before each study intervention) and Day 29 and Day 113 (28 days after each study intervention)
    Notes
    [77] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        Day 1
    2
    3
        Day 29
    10
    3
        Day 85
    10
    3
        Day 113
    10
    2
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg - safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg - safety cohort [78]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, safety cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
    Notes
    [78] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    10
    10
    30
    Units: Participants
        Day 1
    0
    0
    0
    0
        Day 29
    0
    0
    0
    0
        Day 85
    0
    0
    0
    0
        Day 113
    5
    3
    3
    0
        Day 253
    3
    0
    0
    0
        Day 281
    5
    3
    2
    0
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 24 to 59 months of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg [79]
    End point description
    The analysis was performed on the PPS for Stage 2 Children.
    End point type
    Secondary
    End point timeframe
    At Day 1 and Day 85 (before each study intervention) and Day 29 and Day 113 (28 days after each study intervention)
    Notes
    [79] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        Day 1
    0
    1
    1
        Day 29
    7
    6
    0
        Day 85
    7
    6
    1
        Day 113
    7
    6
    3
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg - dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg - dose-finding cohort [80]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
    Notes
    [80] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        Day 1
    1
    0
    2
    0
        Day 29
    2
    0
    2
    0
        Day 85
    2
    2
    1
    1
        Day 113
    38
    36
    36
    1
        Day 253
    18
    20
    28
    2
        Day 281
    40
    45
    47
    2
    No statistical analyses for this end point

    Secondary: Stage 1: Number of participants 18 to 50 years of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA

    		 Close Top of page
    End point title
    		 Stage 1: Number of participants 18 to 50 years of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA [81]
    End point description
    S. sonnei (S.s), S. flexneri 1b (S.f1b), S. flexneri 2a (S.f2a), and S. flexneri 3a (S.f3a) serotypes were tested. 9999 = data not available. The analysis was performed on the PPS for Stage 1 Adults. As the participants in Stage 1 Adults: Placebo Group received the second placebo intervention at Day 85 or at Day 169, the analysis being performed on the pooled participants as per the SAP, no differentiation was made by timepoint of administration for the second dose for this group.
    End point type
    Secondary
    End point timeframe
    At Day 15 (14 days after the first study intervention) and at Day 29 and Day 113/Day 197 (28 days after each study intervention) compared to baseline (Day 1 and Day 85/Day 169)
    Notes
    [81] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 1 Adults: Placebo Group
    Number of subjects analysed
    34
    34
    32
    Units: Participants
        S.s Ab IgG, Day15 compared to Day1
    25
    27
    0
        S.s Ab IgG, Day29 compared to Day1
    26
    26
    0
        S.s Ab IgG, Day113 compared to Day85
    0
    9999
    9999
        S.s Ab IgG, Day197 compared to Day169
    9999
    4
    9999
        S.s Ab IgG, Day113/197 compared to Day85/169
    9999
    9999
    0
        S.f1b Ab IgG, Day15 compared to Day1
    17
    16
    0
        S.f1b Ab IgG, Day29 compared to Day1
    15
    14
    0
        S.f1b Ab IgG, Day113 compared to Day85
    2
    9999
    9999
        S.f1b Ab IgG, Day197 compared to Day169
    9999
    1
    9999
        S.f1b Ab IgG, Day113/197 compared to Day85/169
    9999
    9999
    0
        S.f2a Ab IgG, Day15 compared to Day 1
    32
    31
    0
        S.f2a Ab IgG, Day29 compared to Day1
    30
    31
    0
        S.f2a Ab IgG, Day113 compared to Day85
    1
    9999
    9999
        S.f2a Ab IgG, Day197 compared to Day169
    9999
    0
    9999
        S.f2a Ab IgG, Day113/197 compared to Day85/169
    9999
    9999
    1
        S.f3a Ab IgG, Day15 compared to Day1
    12
    17
    0
        S.f3a Ab IgG, Day29 compared to Day1
    12
    17
    0
        S.f3a Ab IgG, Day113 compared to Day85
    3
    9999
    9999
        S.f3a Ab IgG, Day197 compared to Day169
    9999
    1
    9999
        S.f3a Ab IgG, Day113/197 compared to Day85/169
    9999
    9999
    0
        S.s Ab IgG, Day 85 compared to Day 1
    22
    9999
    9999
        S.s Ab IgG, Day 169 compared to Day 1
    9999
    21
    9999
        S.s Ab IgG, Day 85/169 compared to Day 1
    9999
    9999
    0
        S.s Ab IgG, Day 113 compared to Day 1
    22
    9999
    9999
        S.s Ab IgG, Day 197 compared to Day 85
    9999
    26
    9999
        S.s Ab IgG, Day 113/197 compared to Day 1
    9999
    9999
    0
        S.f1b Ab IgG, Day 85 compared to Day 1
    7
    9999
    9999
        S.f1b Ab IgG, Day 85/169 compared to Day 1
    9999
    9999
    0
        S.f1b Ab IgG, Day 113 compared to Day 1
    11
    9999
    9999
        S.f1b Ab IgG, Day 197 compared to Day 1
    9999
    10
    9999
        S.f1b Ab IgG, Day 113/197 compared to Day 1
    9999
    9999
    0
        S.f2a Ab IgG, Day 85 compared to Day 1
    27
    9999
    9999
        S.f2a Ab IgG, Day 169 compared to Day 1
    9999
    31
    9999
        S.f2a Ab IgG, Day 85/169 compared to Day 1
    9999
    9999
    0
        S.f2a Ab IgG, Day 113 compared to Day 1
    26
    9999
    9999
        S.f2a Ab IgG, Day 197 compared to Day 1
    9999
    32
    9999
        S.f2a Ab IgG, Day 113/197 compared to Day 1
    9999
    9999
    0
        S.f3a Ab IgG, Day 85 compared to Day 1
    2
    9999
    9999
        S.f3a Ab IgG, Day 169 compared to Day 1
    9999
    4
    9999
        S.f3a Ab IgG, Day 85/169 compared to Day 1
    9999
    9999
    0
        S.f3a Ab IgG, Day 113 compared to Day 1
    6
    9999
    9999
        S.f3a Ab IgG, Day 197 compared to Day 1
    9999
    9
    9999
        S.f3a Ab IgG, Day 113/197 compared to Day 1
    9999
    9999
    0
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 18 to 50 years of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 18 to 50 years of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA [82]
    End point description
    The analysis was performed on the PPS for Stage 2 Adults.
    End point type
    Secondary
    End point timeframe
    At Day 29 and Day 113 (28 days after each study intervention) compared to baseline (Day 1 and Day 85)
    Notes
    [82] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control
    Number of subjects analysed
    10
    10
    Units: Participants
        S sonnei Ab IgG, Day 29 compared to Day 1
    10
    0
        S sonnei Ab IgG, Day 85 compared to Day 1
    10
    0
        S sonnei Ab IgG, Day 113 compared to Day 1
    10
    0
        S Sonnei Ab IgG, Day 113 compared to Day 85
    0
    0
        S flexneri 1b Ab IgG, Day 29 compared to Day 1
    2
    0
        S flexneri 1b Ab IgG, Day 85 compared to Day 1
    1
    0
        S flexneri 1b Ab IgG, Day 113 compared to Day 1
    1
    0
        S flexneri 1b Ab IgG, Day 113 compared to Day 85
    0
    0
        S flexneri 2a Ab IgG, Day 29 compared to Day 1
    3
    0
        S flexneri 2a Ab IgG, Day 85 compared to Day 1
    2
    0
        S flexneri 2a Ab IgG, Day 113 compared to Day 1
    3
    0
        S flexneri 2a Ab IgG, Day 113 compared to Day 85
    0
    0
        S flexneri 3a Ab IgG, Day 29 compared to Day 1
    4
    0
        S flexneri 3a Ab IgG, Day 85 compared to Day 1
    2
    0
        S flexneri 3a Ab IgG, Day 113 compared to Day 1
    3
    0
        S flexneri 3a Ab IgG, Day 113 compared to Day 85
    0
    0
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 24 to 59 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 24 to 59 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA [83]
    End point description
    The analysis was performed on the PPS for Stage 2 Children.
    End point type
    Secondary
    End point timeframe
    At Day 29 and Day 113 (28 days after each study intervention) compared to baseline (Day 1 and Day 85)
    Notes
    [83] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 Children: Control
    Number of subjects analysed
    10
    10
    20
    Units: Participants
        S sonnei Ab IgG, Day 29 compared to Day 1
    7
    5
    1
        S sonnei Ab IgG, Day 85 compared to Day 1
    7
    5
    3
        S sonnei Ab IgG, Day 113 compared to Day 1
    10
    6
    5
        S sonnei Ab IgG, Day 113 compared to Day 85
    1
    1
    3
        S flexneri 1b Ab IgG, Day 29 compared to Day 1
    2
    4
    1
        S flexneri 1b Ab IgG, Day 85 compared to Day 1
    0
    1
    1
        S flexneri 1b Ab IgG, Day 113 compared to Day 1
    2
    3
    1
        S flexneri 1b Ab IgG, Day 113 compared to Day 85
    0
    0
    1
        S flexneri 2a Ab IgG, Day 29 compared to Day 1
    6
    6
    0
        S flexneri 2a Ab IgG, Day 85 compared to Day 1
    3
    5
    1
        S flexneri 2a Ab IgG, Day 113 compared to Day 1
    7
    10
    0
        S flexneri 2a Ab IgG, Day 113 compared to Day 85
    3
    2
    0
        S flexneri 3a Ab IgG, Day 29 compared to Day 1
    0
    3
    0
        S flexneri 3a Ab IgG, Day 85 compared to Day 1
    0
    1
    0
        S flexneri 3a Ab IgG, Day 113 compared to Day 1
    1
    3
    1
        S flexneri 3a Ab IgG, Day 113 compared to Day 85
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA - safety cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA - safety cohort [84]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, safety cohort.
    End point type
    Secondary
    End point timeframe
    At Day 29, Day 113 and Day 281 (28 days after each study intervention) compared to baseline (Day 1, Day 85 and Day 253)
    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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose Stage 2 Infants safety cohort: Control
    Number of subjects analysed
    10
    9
    10
    30
    Units: Participants
        S sonnei Ab IgG, Day 29 compared to Day 1
    2
    0
    1
    0
        S sonnei Ab IgG, Day 85 compared to Day 1
    2
    1
    3
    0
        S sonnei Ab IgG, Day 113 compared to Day 1
    8
    8
    9
    0
        S sonnei Ab IgG, Day 113 compared to Day 85
    7
    6
    7
    0
        S sonnei Ab IgG, Day 253 compared to Day 1
    8
    6
    6
    0
        S sonnei Ab IgG, Day 281 compared to Day 1
    9
    7
    9
    0
        S sonnei Ab IgG, Day 281 compared to Day 253
    3
    2
    2
    0
        S flexneri 1b Ab IgG, Day 29 compared to Day 1
    3
    1
    1
    0
        S flexneri 1b Ab IgG, Day 85 compared to Day 1
    1
    0
    0
    3
        S flexneri 1b Ab IgG, Day 113 compared to Day 1
    3
    0
    2
    3
        S flexneri 1b Ab IgG, Day 113 compared to Day 85
    2
    0
    2
    1
        S flexneri 1b Ab IgG, Day 253 compared to Day 1
    1
    0
    1
    5
        S flexneri 1b Ab IgG, Day 281 compared to Day 1
    3
    2
    4
    3
        S flexneri 1b Ab IgG, Day 281 compared to Day 253
    1
    1
    2
    0
        S flexneri 2a Ab IgG, Day 29 compared to Day 1
    6
    5
    5
    3
        S flexneri 2a Ab IgG, Day 85 compared to Day 1
    4
    3
    3
    3
        S flexneri 2a Ab IgG, Day 113 compared to Day 1
    8
    6
    9
    6
        S flexneri 2a Ab IgG, Day 113 compared to Day 85
    1
    4
    5
    3
        S flexneri 2a Ab IgG, Day 253 compared to Day 1
    2
    2
    4
    8
        S flexneri 2a Ab IgG, Day 281 compared to Day 1
    8
    7
    7
    7
        S flexneri 2a Ab IgG, Day 281 compared to Day 253
    6
    5
    7
    0
        S flexneri 3a Ab IgG, Day 29 compared to Day 1
    4
    2
    0
    2
        S flexneri 3a Ab IgG, Day 85 compared to Day 1
    0
    0
    0
    2
        S flexneri 3a Ab IgG, Day 113 compared to Day 1
    3
    1
    0
    1
        S flexneri 3a Ab IgG, Day 113 compared to Day 85
    2
    0
    0
    0
        S flexneri 3a Ab IgG, Day 253 compared to Day 1
    2
    2
    0
    3
        S flexneri 3a Ab IgG, Day 281 compared to Day 1
    4
    4
    3
    2
        S flexneri 3a Ab IgG, Day 281 compared to Day 253
    3
    1
    3
    1
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA - dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA - dose-finding cohort [85]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    At Day 29, Day 113 and Day 281 (28 days after each study intervention) compared to baseline (Day 1, Day 85 and Day 253)
    Notes
    [85] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        S sonnei Ab IgG, Day 29 compared to Day 1
    20
    30
    24
    0
        S sonnei Ab IgG, Day 85 compared to Day 1
    28
    29
    20
    3
        S sonnei Ab IgG, Day 113 compared to Day 1
    57
    61
    64
    2
        S sonnei Ab IgG, Day 113 compared to Day 85
    19
    15
    15
    0
        S sonnei Ab IgG, Day 253 compared to Day 1
    53
    60
    58
    11
        S sonnei Ab IgG, Day 281 compared to Day 1
    62
    62
    69
    12
        S sonnei Ab IgG, Day 281 compared to Day 253
    7
    4
    8
    1
        S flexneri 1b Ab IgG, Day 29 compared to Day 1
    22
    24
    18
    3
        S flexneri 1b Ab IgG, Day 85 compared to Day 1
    7
    9
    5
    3
        S flexneri 1b Ab IgG, Day 113 compared to Day 1
    17
    13
    11
    1
        S flexneri 1b Ab IgG, Day 113 compared to Day 85
    5
    2
    4
    1
        S flexneri 1b Ab IgG, Day 253 compared to Day 1
    10
    3
    4
    12
        S flexneri 1b Ab IgG, Day 281 compared to Day 1
    31
    29
    25
    13
        S flexneri 1b Ab IgG, Day 281 compared to Day 253
    19
    15
    13
    1
        S flexneri 2a Ab IgG, Day 29 compared to Day 1
    50
    52
    49
    3
        S flexneri 2a Ab IgG, Day 85 compared to Day 1
    22
    24
    24
    8
        S flexneri 2a Ab IgG, Day 113 compared to Day 1
    54
    52
    58
    7
        S flexneri 2a Ab IgG, Day 113 compared to Day 85
    39
    36
    42
    3
        S flexneri 2a Ab IgG, Day 253 compared to Day 1
    30
    27
    29
    18
        S flexneri 2a Ab IgG, Day 281 compared to Day 1
    59
    59
    65
    16
        S flexneri 2a Ab IgG, Day 281 compared to Day 253
    41
    48
    52
    3
        S flexneri 3a Ab IgG, Day 29 compared to Day 1
    15
    25
    14
    3
        S flexneri 3a Ab IgG, Day 85 compared to Day 1
    13
    20
    9
    10
        S flexneri 3a Ab IgG, Day 113 compared to Day 1
    26
    25
    22
    9
        S flexneri 3a Ab IgG, Day 113 compared to Day 85
    16
    8
    14
    2
        S flexneri 3a Ab IgG, Day 253 compared to Day 1
    17
    15
    16
    18
        S flexneri 3a Ab IgG, Day 281 compared to Day 1
    36
    36
    41
    17
        S flexneri 3a Ab IgG, Day 281 compared to Day 253
    22
    18
    30
    2
    No statistical analyses for this end point

    Secondary: Stage 2: Anti-measles IgG concentrations in participants 9 months of age in the dose-finding cohort

    		 Close Top of page
    End point title
    		 Stage 2: Anti-measles IgG concentrations in participants 9 months of age in the dose-finding cohort [86]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1 (before first measles and rubella vaccine (MR-VAC)) and at Day 281 (28 days after the second MR-VAC administration)
    Notes
    [86] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Day 1
    26.2 (23.8 to 28.9)
    25.4 (24.6 to 26.1)
    25 (25 to 25)
    26.2 (24.5 to 28.1)
        Day 281
    1204.4 (1043.2 to 1390.6)
    1099.7 (957.2 to 1263.4)
    1142.5 (983 to 1327.9)
    971.4 (793.2 to 1189.7)
    No statistical analyses for this end point

    Secondary: Stage 2: Anti-rubella IgG concentrations in participants 9 months of age in the dose-finding groups

    		 Close Top of page
    End point title
    		 Stage 2: Anti-rubella IgG concentrations in participants 9 months of age in the dose-finding groups [87]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    At Day 1 (before first measles and rubella vaccine (MR-VAC)) and at Day 281 (28 days after the second MR-VAC administration)
    Notes
    [87] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Day 1
    1.2 (1 to 1.4)
    1 (1 to 1)
    1.1 (1 to 1.3)
    1.1 (1 to 1.1)
        Day 281
    138.2 (124.7 to 153.1)
    110.3 (99.6 to 122.1)
    116.4 (105.1 to 129)
    107.1 (89.9 to 127.5)
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age in the dose-finding groups achieving anti-measles IgG concentrations of ≥150 milli international units per milliliter (mIU/mL) and ≥200 mIU/mL

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in the dose-finding groups achieving anti-measles IgG concentrations of ≥150 milli international units per milliliter (mIU/mL) and ≥200 mIU/mL [88]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    Day 281 (28 days after the second MR-VAC administration)
    Notes
    [88] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        >= 150 mIU/mL, Day 281
    66
    64
    71
    68
        >= 200 mIU/mL, Day 281
    66
    64
    71
    67
    No statistical analyses for this end point

    Secondary: Stage 2: Number of participants 9 months of age in the dose-finding groups achieving anti-rubella IgG concentrations of ≥4 mIU/mL and ≥10 mIU/mL

    		 Close Top of page
    End point title
    		 Stage 2: Number of participants 9 months of age in the dose-finding groups achieving anti-rubella IgG concentrations of ≥4 mIU/mL and ≥10 mIU/mL [89]
    End point description
    The analysis was performed on the PPS for Stage 2 Infants, dose-finding cohort.
    End point type
    Secondary
    End point timeframe
    Day 281 (28 days after the second MR-VAC administration)
    Notes
    [89] - 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: As per study design, this endpoint presents analysis of a specific set of participants, hence only the arms included in the specified stage and cohorts are included in the analysis.
    End point values
    		 Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Med Dose Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 Infants dose-finding cohort: Control
    Number of subjects analysed
    82
    81
    83
    82
    Units: Participants
        >= 4 IU/mL Day 281
    66
    64
    71
    68
        >= 10 IU/mL Day 281
    66
    64
    71
    68
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Solicited AEs were collected within 7 days and unsolicited AEs within 28 days after any intervention (administered on Day (D) 1 and D85 for Stage 1 adults, Stage 2 adults and children and D1, D85 and D253 for Stage 2 infants).
    Adverse event reporting additional description
    SAEs and all-cause mortality: from Day (D) 1 to D113/D197 for Stage 1, from D1 to D113 for Stage 2 adults & children, from D1 to D281 for Stage 2 infants.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 v28.0
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Stage 1 Adults: altSonflex1-2-3 High Dose Group 1
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive 1 dose of altSonflex1-2-3 High Dose on Day 1 and Day 85

    Reporting group title
    Stage 1 Adults: altSonflex1-2-3 High Dose Group 2
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive 1 dose of altSonflex1-2-3 High Dose on Day 1 and Day 169

    Reporting group title
    Stage 2 Infants: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of altSonflex1-2-3 high dose on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of altSonflex1-2-3 medium dose on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Infants: altSonflex1-2-3 Low Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of altSonflex1-2-3 low dose on Day 1, Day 85 and Day 253. The measles-rubella vaccine (MR-VAC) was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 Chilren: Control
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of TYPHIM VI as comparator on Day 85.

    Reporting group title
    Stage 1 Adults: Placebo Group
    Reporting group description
    		 European participants 18-50 years of age were randomized to receive 1 dose of Placebo on Day 1 and on Day 85 or 169. All participants that received placebo were pooled, as per SAP.

    Reporting group title
    Stage 2 Adults: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 18-50 years of age were randomized to receive 1 dose of altSonflex1-2-3 high dose on Day 1 and Day 85

    Reporting group title
    Stage 2 Adults: Control
    Reporting group description
    		 African participants 18-50 years of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of BOOSTRIX as comparator Day 85

    Reporting group title
    Stage 2 Children: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive a dose of altSonflex1-2-3 medium dose on Day 1 and Day 85.

    Reporting group title
    Stage 2 Children: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 24-59 months of age were randomized to receive a dose of altSonflex1-2-3 high dose on Day 1 and Day 85.

    Reporting group title
    Stage 2 dose-finding cohort: altSonflex1-2-3 Medium Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of altSonflex1-2-3 medium dose on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was evaluated to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 dose-finding cohort: altSonflex1-2-3 Low Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of altSonflex1-2-3 low dose on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was evaluated to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 Infants: Control
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.

    Reporting group title
    Stage 2 dose-finding cohort: altSonflex1-2-3 High Dose
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of altSonflex1-2-3 high dose on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was evaluated to identify the preferred dose among low, medium and high doses.

    Reporting group title
    Stage 2 dose-finding cohort: Control
    Reporting group description
    		 African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was evaluated to identify the preferred dose among low, medium and high doses.

    Serious adverse events
    		 Stage 1 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 2 Infants: altSonflex1-2-3 High Dose Stage 2 Infants: altSonflex1-2-3 Medium Dose Stage 2 Infants: altSonflex1-2-3 Low Dose Stage 2 Chilren: Control Stage 1 Adults: Placebo Group Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 dose-finding cohort: altSonflex1-2-3 Medium Dose Stage 2 dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants: Control Stage 2 dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 dose-finding cohort: Control
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    2 / 82 (2.44%)
    1 / 30 (3.33%)
    4 / 83 (4.82%)
    1 / 82 (1.22%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Thermal burn
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Infantile spasms
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Stomatitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    1 / 30 (3.33%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    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
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    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
    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 Adults: altSonflex1-2-3 High Dose Group 1 Stage 1 Adults: altSonflex1-2-3 High Dose Group 2 Stage 2 Infants: altSonflex1-2-3 High Dose Stage 2 Infants: altSonflex1-2-3 Medium Dose Stage 2 Infants: altSonflex1-2-3 Low Dose Stage 2 Chilren: Control Stage 1 Adults: Placebo Group Stage 2 Adults: altSonflex1-2-3 High Dose Stage 2 Adults: Control Stage 2 Children: altSonflex1-2-3 Medium Dose Stage 2 Children: altSonflex1-2-3 High Dose Stage 2 dose-finding cohort: altSonflex1-2-3 Medium Dose Stage 2 dose-finding cohort: altSonflex1-2-3 Low Dose Stage 2 Infants: Control Stage 2 dose-finding cohort: altSonflex1-2-3 High Dose Stage 2 dose-finding cohort: Control
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    33 / 34 (97.06%)
    33 / 34 (97.06%)
    10 / 10 (100.00%)
    8 / 10 (80.00%)
    6 / 10 (60.00%)
    12 / 20 (60.00%)
    32 / 34 (94.12%)
    7 / 10 (70.00%)
    5 / 10 (50.00%)
    9 / 10 (90.00%)
    5 / 10 (50.00%)
    74 / 81 (91.36%)
    77 / 82 (93.90%)
    26 / 30 (86.67%)
    80 / 83 (96.39%)
    69 / 82 (84.15%)
    General disorders and administration site conditions
    Administration site erythema
         subjects affected / exposed
    5 / 34 (14.71%)
    8 / 34 (23.53%)
    6 / 10 (60.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    21 / 81 (25.93%)
    20 / 82 (24.39%)
    1 / 30 (3.33%)
    32 / 83 (38.55%)
    14 / 82 (17.07%)
         occurrences all number
    6
    10
    9
    1
    0
    0
    1
    0
    0
    2
    1
    28
    33
    1
    43
    21
    Axillary pain
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Administration site swelling
         subjects affected / exposed
    5 / 34 (14.71%)
    9 / 34 (26.47%)
    5 / 10 (50.00%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 10 (10.00%)
    32 / 81 (39.51%)
    30 / 82 (36.59%)
    5 / 30 (16.67%)
    34 / 83 (40.96%)
    20 / 82 (24.39%)
         occurrences all number
    7
    12
    11
    2
    1
    0
    0
    0
    0
    2
    1
    53
    55
    6
    60
    25
    Application site hypersensitivity
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Administration site pain
         subjects affected / exposed
    33 / 34 (97.06%)
    33 / 34 (97.06%)
    7 / 10 (70.00%)
    5 / 10 (50.00%)
    4 / 10 (40.00%)
    3 / 20 (15.00%)
    20 / 34 (58.82%)
    7 / 10 (70.00%)
    4 / 10 (40.00%)
    7 / 10 (70.00%)
    3 / 10 (30.00%)
    57 / 81 (70.37%)
    49 / 82 (59.76%)
    7 / 30 (23.33%)
    58 / 83 (69.88%)
    35 / 82 (42.68%)
         occurrences all number
    54
    64
    20
    10
    6
    6
    24
    9
    5
    13
    4
    117
    101
    12
    127
    60
    Chills
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    4 / 34 (11.76%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    5
    1
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site eczema
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    3 / 34 (8.82%)
    5 / 34 (14.71%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    4 / 34 (11.76%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    4
    5
    0
    0
    0
    0
    4
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site discolouration
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Feeling hot
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    1 / 83 (1.20%)
    1 / 82 (1.22%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    1
    1
    1
    Injection site erythema
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site haematoma
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site induration
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site reaction
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    1 / 34 (2.94%)
    3 / 34 (8.82%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site rash
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Injection site nodule
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Injection site warmth
         subjects affected / exposed
    0 / 34 (0.00%)
    3 / 34 (8.82%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Malaise
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Vaccination site pain
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 34 (2.94%)
    5 / 10 (50.00%)
    3 / 10 (30.00%)
    1 / 10 (10.00%)
    3 / 20 (15.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 10 (20.00%)
    2 / 10 (20.00%)
    28 / 81 (34.57%)
    38 / 82 (46.34%)
    9 / 30 (30.00%)
    37 / 83 (44.58%)
    18 / 82 (21.95%)
         occurrences all number
    2
    1
    6
    3
    2
    3
    1
    0
    0
    2
    2
    35
    48
    10
    44
    22
    Swelling face
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Immune system disorders
    Food allergy
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Reproductive system and breast disorders
    Vaginal discharge
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Nasal congestion
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Cough
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 34 (2.94%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    6 / 82 (7.32%)
    2 / 30 (6.67%)
    9 / 83 (10.84%)
    10 / 82 (12.20%)
         occurrences all number
    1
    1
    1
    0
    0
    1
    0
    0
    0
    0
    0
    2
    6
    2
    9
    10
    Bronchospasm
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    1 / 83 (1.20%)
    2 / 82 (2.44%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    1
    2
    Allergic cough
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    5 / 81 (6.17%)
    3 / 82 (3.66%)
    0 / 30 (0.00%)
    6 / 83 (7.23%)
    5 / 82 (6.10%)
         occurrences all number
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    5
    3
    0
    6
    5
    Sneezing
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Pulmonary congestion
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 34 (5.88%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    3 / 34 (8.82%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    3
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nasal discomfort
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    2 / 82 (2.44%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    0
    1
    1
    Blood potassium increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood sodium increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Blood thyroid stimulating hormone increased
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Eosinophil count increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Haemoglobin decreased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    3 / 81 (3.70%)
    8 / 82 (9.76%)
    0 / 30 (0.00%)
    5 / 83 (6.02%)
    3 / 82 (3.66%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    3
    8
    0
    5
    3
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Lymphocyte count increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    3 / 82 (3.66%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    3
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    2 / 82 (2.44%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    2
    Platelet count increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    4 / 82 (4.88%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    2
    4
    0
    0
    1
    Respiratory rate increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Bone contusion
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Face injury
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Immunisation reaction
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hand fracture
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Greenstick fracture
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Limb injury
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Soft tissue injury
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Thermal burn
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Syncope
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Partial seizures
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Migraine
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypotonia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    12 / 34 (35.29%)
    10 / 34 (29.41%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    8 / 34 (23.53%)
    3 / 10 (30.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    16
    13
    0
    0
    0
    0
    13
    3
    1
    0
    0
    0
    0
    0
    0
    0
    Tension headache
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Lymph node pain
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    8 / 82 (9.76%)
    0 / 30 (0.00%)
    6 / 83 (7.23%)
    3 / 82 (3.66%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    1
    9
    0
    7
    3
    Thrombocytopenia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Thrombocytosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Ear and labyrinth disorders
    Hypoacusis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Eye disorders
    Conjunctivitis allergic
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Eye irritation
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Lacrimation increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Eye pruritus
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Cheilitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Constipation
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    1 / 82 (1.22%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    1
    Flatulence
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Enteritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    2 / 82 (2.44%)
    0 / 30 (0.00%)
    2 / 83 (2.41%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    0
    2
    1
    Faeces hard
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    2 / 82 (2.44%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    2
    Diarrhoea
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    15 / 81 (18.52%)
    4 / 82 (4.88%)
    3 / 30 (10.00%)
    5 / 83 (6.02%)
    14 / 82 (17.07%)
         occurrences all number
    0
    0
    2
    0
    0
    0
    2
    0
    0
    0
    1
    15
    4
    3
    5
    15
    Gastritis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Toothache
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Mucous stools
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Mouth ulceration
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    1 / 82 (1.22%)
    1 / 30 (3.33%)
    3 / 83 (3.61%)
    4 / 82 (4.88%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    1
    3
    5
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    3 / 81 (3.70%)
    2 / 82 (2.44%)
    0 / 30 (0.00%)
    5 / 83 (6.02%)
    3 / 82 (3.66%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    3
    2
    0
    5
    4
    Blister
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Dermatitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    2 / 83 (2.41%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    1
    0
    2
    1
    Eczema
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Urticaria
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Rash pruritic
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Endocrine disorders
    Autoimmune hypothyroidism
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Limb discomfort
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Groin pain
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Neck pain
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Myalgia intercostal
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Muscle tightness
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Body tinea
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    Amoebic dysentery
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Bacterial infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Amoebiasis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 20 (10.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Bronchiolitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    COVID-19
         subjects affected / exposed
    4 / 34 (11.76%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    6 / 34 (17.65%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    4
    1
    0
    0
    0
    0
    6
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Dermatitis infected
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    2 / 83 (2.41%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    2
    0
    1
    2
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    3 / 81 (3.70%)
    2 / 82 (2.44%)
    4 / 30 (13.33%)
    1 / 83 (1.20%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    3
    2
    4
    1
    1
    Cystitis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Cellulitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Ear infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Genital abscess
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    8 / 81 (9.88%)
    3 / 82 (3.66%)
    0 / 30 (0.00%)
    11 / 83 (13.25%)
    8 / 82 (9.76%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    1
    0
    0
    0
    0
    9
    4
    0
    12
    8
    Furuncle
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    Helminthic infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Infectious mononucleosis
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Labyrinthitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    1
    1
    Malaria
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 20 (5.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    0
    0
    1
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 34 (2.94%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    6 / 81 (7.41%)
    6 / 82 (7.32%)
    2 / 30 (6.67%)
    5 / 83 (6.02%)
    1 / 82 (1.22%)
         occurrences all number
    2
    1
    1
    0
    1
    0
    1
    0
    0
    0
    0
    6
    6
    2
    5
    1
    Oral candidiasis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    3 / 82 (3.66%)
    0 / 30 (0.00%)
    5 / 83 (6.02%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    3
    0
    6
    1
    Otitis media
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    1 / 30 (3.33%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    0
    0
    0
    0
    1
    0
    0
    1
    0
    0
    Otitis media acute
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 81 (1.23%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    1
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    1 / 82 (1.22%)
    1 / 30 (3.33%)
    0 / 83 (0.00%)
    2 / 82 (2.44%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    1
    0
    0
    0
    0
    2
    1
    1
    0
    2
    Plasmodium falciparum infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    0 / 82 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    1 / 81 (1.23%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    1 / 83 (1.20%)
    2 / 82 (2.44%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    1
    0
    0
    1
    2
    Rhinitis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 34 (5.88%)
    4 / 10 (40.00%)
    2 / 10 (20.00%)
    2 / 10 (20.00%)
    2 / 20 (10.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    9 / 81 (11.11%)
    7 / 82 (8.54%)
    6 / 30 (20.00%)
    6 / 83 (7.23%)
    13 / 82 (15.85%)
         occurrences all number
    0
    2
    5
    2
    3
    2
    0
    0
    0
    1
    0
    11
    7
    7
    8
    13
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 34 (0.00%)
    2 / 10 (20.00%)
    1 / 10 (10.00%)
    2 / 10 (20.00%)
    1 / 20 (5.00%)
    2 / 34 (5.88%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    2 / 10 (20.00%)
    0 / 10 (0.00%)
    19 / 81 (23.46%)
    17 / 82 (20.73%)
    8 / 30 (26.67%)
    18 / 83 (21.69%)
    21 / 82 (25.61%)
         occurrences all number
    2
    0
    2
    2
    2
    1
    2
    0
    1
    2
    0
    21
    21
    8
    21
    23
    Scabies
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Sinusitis
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    0 / 82 (0.00%)
         occurrences all number
    2
    2
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 34 (2.94%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    1 / 10 (10.00%)
    0 / 10 (0.00%)
    3 / 81 (3.70%)
    3 / 82 (3.66%)
    1 / 30 (3.33%)
    3 / 83 (3.61%)
    3 / 82 (3.66%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    1
    0
    1
    0
    3
    3
    1
    3
    3
    Varicella
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    2 / 81 (2.47%)
    1 / 82 (1.22%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    0
    2
    1
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 20 (0.00%)
    0 / 34 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 10 (0.00%)
    0 / 81 (0.00%)
    0 / 82 (0.00%)
    0 / 30 (0.00%)
    0 / 83 (0.00%)
    1 / 82 (1.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    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
    23 Sep 2021
    This amendment has been prepared based on feedback received from the clinical trial application to the Belgian health authority. The word “booster vaccination” has been replaced by “third vaccination” or “primary” vaccination. The screening period has been shortened to 28 days. Additional rationale have been added for choice of schedule, choice of study population, and justification of dose. Inclusion criterion has been revised to mention that laboratory assessment is used as assessment for healthy participants. Travel and occupational exposure to Shigella have been added to the exclusion criterion on known exposure to Shigella. The criterion on reaction/hypersensitivity to any component of the study vaccine has been clarified. Exceptions for flu and COVID-19 vaccines in adults and EPI vaccines in children and infants have been added to the exclusion criteria. Bone marrow transplantation has been added to the exclusion criteria. Immediate allergic reaction to previous study vaccination has been added as contraindication. Additional clarifications on the additional blood volume collected in some participants for peripheral blood mononuclear cell (PBMC) extraction has been added. Instructions have been added for the investigator or delegate to assess the exclusion criterion of known exposure to Shigella.
    14 Feb 2022
    This amendment has been prepared to incorporate the latest company strategy on result analysis before the first interim analysis data lock point, address operational issues due to the COVID-19 pandemic, and to incorporate feedback received from the Kenyan site Institutional Review Boards (IRB). An additional benefit is added for children and infants participants who did not receive MENVEO during the study so they can receive a meningitis vaccine at the end of the study. GVGH will also play a role in supporting revaccination of non-responder with measles and rubella vaccines in Stage 2. In case the Quantitative Decision Making (QDM) success criterion is not met during Interim Analysis 1, a comprehensive review of all Stage 1 immunogenicity and safety data (Interim analysis 2) will lead to the GO-NO-GO decision to proceed to Stage 2 (instead on relying only on QDM). Changes have been made due to the COVID-19 pandemic The 3rd and 4th interim analyses have been combined into 1 interim analysis. Other minor changes have been made.
    07 Feb 2023
    This amendment has been prepared due to a change of the laboratory performing primary and secondary immunogenicity analyses, the addition of endpoints for serum bactericidal assay, and the inclusion of an additional interim analysis for the infant safety cohort.
    31 Oct 2023
    The amendment has been prepared to improve safety monitoring of participants by modifying the creatinine grading scale using a range that better represents the population being evaluated and by introducing blood urea, sodium, and potassium testing to ensure further monitoring of renal function. Serology sampling has been optimised to obtain more representative results with reference ELISA testing and focus on immune response characterization. Due to supply constraints, the trivalent INFANRIX vaccine is also being substituted with the hexavalent INFANRIX HEXA vaccine providing additional potential benefit to the participants.

    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.
    Limitations of the trial were small numbers of participants analyzed for the adults and children cohorts. Short study follow-up (1 month after last vaccination) did not allow for the assessment of the persistence of immune responses.
    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-Sun Jan 18 00:47:53 CET 2026 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA