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   44068   clinical trials with a EudraCT protocol, of which   7320   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 Study in Patients with Hard-to-Heal Venous Leg Ulcers to Measure Efficacy and Safety of Locally Administered LL-37; A Phase IIb, Double-blind, Randomised, Placebo-controlled, Multi-centre Trial

    Summary
    EudraCT number
    		 2018-000536-10
    Trial protocol
    		 PL  
    Global end of trial date
    13 Jul 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jul 2021
    First version publication date
    26 Jul 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    LL-37002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Promore Pharma AB
    Sponsor organisation address
    Karolinska Institutet Science Park Fogdevreten 2 , Stockholm, Sweden, SE-171 65
    Public contact
    Margit Mahlapuu Chief Scientific Officer, Promore Pharma AB, +46 706310109, margit.mahlapuu@promorepharma.com
    Scientific contact
    Margit Mahlapuu Chief Scientific Officer, Promore Pharma AB, +46 706310109, margit.mahlapuu@promorepharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    30 Aug 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Jul 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Jul 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to determine the efficacy of LL-37, at concentrations of 0.5 and 1.6 mg/mL, in increasing the incidence of complete wound closure compared with placebo in the treatment of hard-to-heal (HTH) venous leg ulcers (VLUs).
    Protection of trial subjects
    The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements. Informed consent was obtained from all patients prior to initiation of the study. Pain was part of efficacy assessment and was monitored throughout the study using a graded visual analogue scale (VAS) score (0-10). Safety was monitored at all visits based on adverse events (AEs) and local tolerability assessments. The investigator and/or delegated study nurse carefully monitored the treated ulcers with regard to ulcer characteristics at each dressing change, 2 times per week. In order to detect drug-related reactions, patients reported any AEs occuring between dressing changes. Cream containing lidocaine or prilocaine could be used for pain relief before cleansing and dressing both on the wound itself and in surrounding tissues.
    Background therapy
    		 No background therapy was used in the study.
    Evidence for comparator
    		 No comparator was used in the study. The test product was compared to a placebo.
    Actual start date of recruitment
    26 Aug 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 146
    Country: Number of subjects enrolled
    Sweden: 3
    Worldwide total number of subjects
    149
    EEA total number of subjects
    149
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    58
    From 65 to 84 years
    82
    85 years and over
    9

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The first patient was screened and treated in the run-in period on 2018-09-26. The first patient was randomised and treated (during the treatment period) on 2018-10-15. The last patient’s last visit (treatment period) was on 2020 03-20 and the last patient’s last folow-up visit was on 2020-07-13.

    Pre-assignment
    Screening details
    		 Screening was performed in 190 patients. Of those, 149 were randomised. The main reason for screening failure was unfulfilment of inclusion/exclusion criteria. One randomised patient withdrew consent and the remaining 148 paitents entered and completed the run-in period, during which they were treated with placebo and received standart ulcer care.

    Pre-assignment period milestones
    Number of subjects started
    		 149
    Number of subjects completed
    		 149

    Period 1
    Period 1 title
    Randomisation
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    The blinding was broken for analysis of data when all patients completed the treatment period and the post-wound closure visits. To reduce the risk of bias, the blinding was maintained during the follow-up period among patients, site staff and other people not involved in the statistical analysis or writing of the clinical study report.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LL37 0.5 mg/mL group
    Arm description
    		 Patients were allocated to receive 0.5 mg/mL of LL-37 During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 0.5 mg/mL of LL-37 and active doses of 12.5 µg/cm2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LL-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The IMP was provided in glass syringes, which contained 0.4 mL solution. The diluent (13.1% polyvinyl alcohol [PVA]) was provided in a sealed glass vial, containing 5.0 mL solution. The IMP and diluent were shipped and stored temperature-controlled at +2 to +8°C. The syringes and vials provided were intended for single use. The IMP was prepared by mixing 0.4 mL of the test product or placebo with 1.6 mL of diluent immediately before use. The ready-to-use product had to be used within 3 hours after preparation. The doses were selected based on the results of the phase I/II study LL-37001B, which demonstrated the most pronounced effect on early wound healing response for the doses of 0.5 and 1.6 mg/mL. All patients, regardless of treatment group, also received standard ulcer care including appropriate dressing and compression bandaging.

    Arm title
    		 LL37 1.6 mg/mL group
    Arm description
    		 Patients were allocated to receive 1.6 mg/mL of LL-37 During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 1.6 mg/mL of LL-37 and active doses of 40 µg/cm2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LL-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The IMP was provided in glass syringes, which contained 0.4 mL solution. The diluent (13.1% polyvinyl alcohol [PVA]) was provided in a sealed glass vial, containing 5.0 mL solution. The IMP and diluent were shipped and stored temperature-controlled at +2 to +8°C. The syringes and vials provided were intended for single use. The IMP was prepared by mixing 0.4 mL of the test product or placebo with 1.6 mL of diluent immediately before use. The ready-to-use product had to be used within 3 hours after preparation. The doses were selected based on the results of the phase I/II study LL-37001B, which demonstrated the most pronounced effect on early wound healing response for the doses of 0.5 and 1.6 mg/mL. All patients, regardless of treatment group, also received standard ulcer care including appropriate dressing and compression bandaging.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to receive placebo (reference product) every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The reference product, placebo, was identical to the composition of the test product with the exception that it contained no LL-37. The ready-to-use reference product was prepared by mixing the reference product with the diluent provided (13.1% PVA). During the run-in period and the treatment period, the ready-to-use reference product was applied every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.

    Number of subjects in period 1
    		LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Started
    48
    49
    52
    Completed
    48
    49
    51
    Not completed
    0
    0
    1
         Consent withdrawn by subject
    -
    -
    1
    Period 2
    Period 2 title
    Treatment period
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    The blinding was broken for analysis of data when all patients completed the treatment period and the post-wound closure visits. To reduce the risk of bias, the blinding was maintained during the follow-up period among patients, site staff and other people not involved in the statistical analysis or writing of the clinical study report.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LL37 0.5 mg/mL group
    Arm description
    		 Patients were allocated to receive 0.5 mg/mL of LL-37. During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 0.5 mg/mL of LL-37 and active doses of 12.5 µg/cm2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LL-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The IMP was provided in glass syringes, which contained 0.4 mL solution. The diluent (13.1% polyvinyl alcohol [PVA]) was provided in a sealed glass vial, containing 5.0 mL solution. The IMP and diluent were shipped and stored temperature-controlled at +2 to +8°C. The syringes and vials provided were intended for single use. The IMP was prepared by mixing 0.4 mL of the test product or placebo with 1.6 mL of diluent immediately before use. The ready-to-use product had to be used within 3 hours after preparation. The doses were selected based on the results of the phase I/II study LL-37001B, which demonstrated the most pronounced effect on early wound healing response for the doses of 0.5 and 1.6 mg/mL. All patients, regardless of treatment group, also received standard ulcer care including appropriate dressing and compression bandaging.

    Arm title
    		 LL37 1.6 mg/mL group
    Arm description
    		 Patients were allocated to receive 1.6 mg/mL of LL-37. During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 1.6 mg/mL of LL-37 and active doses of 40 µg/cm2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LL-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The IMP was provided in glass syringes, which contained 0.4 mL solution. The diluent (13.1% polyvinyl alcohol [PVA]) was provided in a sealed glass vial, containing 5.0 mL solution. The IMP and diluent were shipped and stored temperature-controlled at +2 to +8°C. The syringes and vials provided were intended for single use. The IMP was prepared by mixing 0.4 mL of the test product or placebo with 1.6 mL of diluent immediately before use. The ready-to-use product had to be used within 3 hours after preparation. The doses were selected based on the results of the phase I/II study LL-37001B, which demonstrated the most pronounced effect on early wound healing response for the doses of 0.5 and 1.6 mg/mL. All patients, regardless of treatment group, also received standard ulcer care including appropriate dressing and compression bandaging.

    Arm title
    		 Placebo
    Arm description
    		 Patients were allocated to receive placebo (reference product). The placebo was applied every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The reference product, placebo, was identical to the composition of the test product with the exception that it contained no LL-37. The ready-to-use reference product was prepared by mixing the reference product with the diluent provided (13.1% PVA). During the run-in period and the treatment period, the ready-to-use reference product was applied every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: One patient withdrew after randomisation and before treating. Therefore the total number of patints for whom baseline characteristics are reported is 148; 48 in the LL37 0.5 mg/mL group, 49 in the LL37 1.6 mg/mL group and 51 in the placebo group. By selecting Period 2-Ttreatment period as the baseline period, the correct number of patients is entered in the baseline characteristics report.
    Number of subjects in period 2 [2]
    		LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Started
    48
    49
    51
    Completed
    42
    41
    48
    Not completed
    6
    8
    3
         Consent withdrawn by subject
    2
    4
    2
         Adverse event, non-fatal
    -
    4
    -
         Missing visits
    1
    -
    -
         Lost to follow-up
    1
    -
    -
         Protocol deviation
    2
    -
    1
    Notes
    [2] - 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: One patient withdrew after randomisation and before treatment. Therefore the total number of patients for whom baseline characteristics are reported is 148; 48 in the LL37 0.5 mg/mL group, 49 in the LL37 1.6 mg/mL group and 51 in the placebo group. By selecting Period 2-Ttreatment period as the baseline period, the correct number of patients is entered in the baseline characteristics report.
    Period 3
    Period 3 title
    Follow-up period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    The blinding was broken for analysis of data when all patients completed the treatment period and the post-wound closure visits. To reduce the risk of bias, the blinding was maintained during the follow-up period among patients, site staff and other people not involved in the statistical analysis or writing of the clinical study report.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LL37 0.5 mg/mL group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    LL-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The IMP was provided in glass syringes, which contained 0.4 mL solution. The diluent (13.1% polyvinyl alcohol [PVA]) was provided in a sealed glass vial, containing 5.0 mL solution. The IMP and diluent were shipped and stored temperature-controlled at +2 to +8°C. The syringes and vials provided were intended for single use. The IMP was prepared by mixing 0.4 mL of the test product or placebo with 1.6 mL of diluent immediately before use. The ready-to-use product had to be used within 3 hours after preparation. The doses were selected based on the results of the phase I/II study LL-37001B, which demonstrated the most pronounced effect on early wound healing response for the doses of 0.5 and 1.6 mg/mL. All patients, regardless of treatment group, also received standard ulcer care including appropriate dressing and compression bandaging.

    Arm title
    		 LL37 1.6 mg/mL group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    LL-37
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The IMP was provided in glass syringes, which contained 0.4 mL solution. The diluent (13.1% polyvinyl alcohol [PVA]) was provided in a sealed glass vial, containing 5.0 mL solution. The IMP and diluent were shipped and stored temperature-controlled at +2 to +8°C. The syringes and vials provided were intended for single use. The IMP was prepared by mixing 0.4 mL of the test product or placebo with 1.6 mL of diluent immediately before use. The ready-to-use product had to be used within 3 hours after preparation. The doses were selected based on the results of the phase I/II study LL-37001B, which demonstrated the most pronounced effect on early wound healing response for the doses of 0.5 and 1.6 mg/mL. All patients, regardless of treatment group, also received standard ulcer care including appropriate dressing and compression bandaging.

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Sterile concentrate
    Routes of administration
    Cutaneous use
    Dosage and administration details
    The reference product, placebo, was identical to the composition of the test product with the exception that it contained no LL-37. The ready-to-use reference product was prepared by mixing the reference product with the diluent provided (13.1% PVA). During the run-in period and the treatment period, the ready-to-use reference product was applied every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.

    Number of subjects in period 3
    		LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Started
    42
    41
    48
    8 weeks follow-up
    31
    26
    35
    16 weeks follow-up
    26
    25
    27
    Completed
    26
    25
    27
    Not completed
    16
    16
    21
         Consent withdrawn by subject
    2
    4
    8
         Physician decision
    2
    -
    -
         Other
    1
    3
    1
         Lost to follow-up
    11
    9
    12

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    LL37 0.5 mg/mL group
    Reporting group description
    		 Patients were allocated to receive 0.5 mg/mL of LL-37. During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 0.5 mg/mL of LL-37 and active doses of 12.5 µg/cm2.

    Reporting group title
    LL37 1.6 mg/mL group
    Reporting group description
    		 Patients were allocated to receive 1.6 mg/mL of LL-37. During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 1.6 mg/mL of LL-37 and active doses of 40 µg/cm2.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive placebo (reference product). The placebo was applied every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.

    Reporting group values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo Total
    Number of subjects
    		 48 49 51 148
    Age categorical
    Units: Subjects
        Adults (≥ 18 years)
    		 48 49 51 148
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 67.5 ( 11.6 ) 67.3 ( 11.5 ) 68.5 ( 11.7 ) -
    Gender categorical
    Units: Subjects
        Female
    		 26 28 29 83
        Male
    		 22 21 22 65
    Location of the target ulcer
    History of target ulcer.
    Units: Subjects
        Left leg back
    		 1 3 3 7
        Left leg front
    		 4 3 5 12
        Left leg inner aspect
    		 14 17 12 43
        Left leg outer aspect
    		 8 7 8 23
        Right leg back
    		 0 1 0 1
        Right leg front
    		 8 3 5 16
        Right leg inner aspect
    		 9 5 11 25
        Right leg outer aspect
    		 4 10 7 21
    Prior use of compression therapy
    History of target ulcer.
    Units: Subjects
        Yes
    		 48 49 51 148
        No
    		 0 0 0 0
    Prior use of ulcer dressing
    History of target ulcer.
    Units: Subjects
        Yes
    		 44 46 47 137
        No
    		 4 3 4 11
    Duration of the target ulcer
    History of target ulcer.
    Units: Days
        arithmetic mean (standard deviation)
    		 1590.8 ( 2277.7 ) 1131.3 ( 1388.3 ) 1984.7 ( 2548.7 ) -
    Ankle-brachial pressure index (ABPI)
    Units: No unit
        arithmetic mean (standard deviation)
    		 0.973 ( 0.140 ) 0.993 ( 0.172 ) 1.007 ( 0.980 ) -
    Subject analysis sets

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety analysis set was defined as all patients who received at least one application of the study treatment. Analysis on the safety analysis set was based on actual treatment (i.e. patients were analysed “as treated”).

    Subject analysis set title
    Per-protocol analysis set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per-protocol analysis set (PPAS) was defined as the subset of patients in the FAS who completed the treatment period and for whom no protocol deviation judged as having an impact on the primary efficacy analysis was reported or identified. The decision as to which protocol deviations were considered as reason for exclusion from the PPAS was made at the clean file meeting and documented in the clean file report. Analysis on the PPAS was based on the actual treatment (i.e. patients were analysed “as treated”).

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set (FAS) was defined as all randomised patients who received at least one application of the study treatment and for whom at least one post-baseline ulcer assessment was made. Patients who were randomised in violation of eligibility criteria were excluded from the FAS. The blinding ensured that the decision of whether to begin treatment could not be influenced by knowledge of the assigned treatment, and thus the intention-to-treat principle was preserved despite the exclusion of patients who did not receive any application of the study treatment. The same rationale applied to the exclusion of patients with no post-baseline ulcer assessment, since the first such assessment was performed within a few days after baseline. Analysis on the FAS was based on the planned treatment (i.e. patients were analysed “as randomised”).

    Subject analysis set title
    FAS, sub-group of patients who completed the treatment period
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    FAS, sub-group of patients who completed the treatment period

    Subject analysis set title
    FAS, patients with wound area < 10 cm² at randomisation
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    FAS, patients with wound area < 10 cm² at randomisation

    Subject analysis set title
    FAS, patients with wound area ≥ 10 cm² at randomisation
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    FAS, patients with wound area ≥ 10 cm² at randomisation

    Subject analysis sets values
    		 Safety analysis set Per-protocol analysis set Full analysis set FAS, sub-group of patients who completed the treatment period FAS, patients with wound area < 10 cm² at randomisation FAS, patients with wound area ≥ 10 cm² at randomisation
    Number of subjects
    148
    129
    144
    131
    78
    66
    Age categorical
    Units: Subjects
        Adults (≥ 18 years)
    148
    129
    144
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    67.8 ( 11.5 )
    67.6 ( 11.5 )
    67.6 ( 11.5 )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    83
    74
    80
        Male
    65
    55
    64
    Location of the target ulcer
    History of target ulcer.
    Units: Subjects
        Left leg back
    7
    7
    7
        Left leg front
    12
    11
    12
        Left leg inner aspect
    43
    36
    42
        Left leg outer aspect
    23
    22
    23
        Right leg back
    1
    0
    0
        Right leg front
    16
    12
    14
        Right leg inner aspect
    25
    24
    25
        Right leg outer aspect
    21
    17
    21
    Prior use of compression therapy
    History of target ulcer.
    Units: Subjects
        Yes
    148
    129
    144
        No
    0
    0
    0
    Prior use of ulcer dressing
    History of target ulcer.
    Units: Subjects
        Yes
    137
    120
    134
        No
    11
    9
    10
    Duration of the target ulcer
    History of target ulcer.
    Units: Days
        arithmetic mean (standard deviation)
    1574.4 ( 2149.7 )
    1649.1 ( 2225.0 )
    1577.9 ( 2159.7 )
    ( )
    ( )
    ( )
    Ankle-brachial pressure index (ABPI)
    Units: No unit
        arithmetic mean (standard deviation)
    0.991 ( 0.153 )
    0.990 ( 0.158 )
    0.988 ( 0.154 )
    ( )
    ( )
    ( )

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    LL37 0.5 mg/mL group
    Reporting group description
    		 Patients were allocated to receive 0.5 mg/mL of LL-37 During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 0.5 mg/mL of LL-37 and active doses of 12.5 µg/cm2.

    Reporting group title
    LL37 1.6 mg/mL group
    Reporting group description
    		 Patients were allocated to receive 1.6 mg/mL of LL-37 During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 1.6 mg/mL of LL-37 and active doses of 40 µg/cm2.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive placebo (reference product) every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.
    Reporting group title
    LL37 0.5 mg/mL group
    Reporting group description
    		 Patients were allocated to receive 0.5 mg/mL of LL-37. During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 0.5 mg/mL of LL-37 and active doses of 12.5 µg/cm2.

    Reporting group title
    LL37 1.6 mg/mL group
    Reporting group description
    		 Patients were allocated to receive 1.6 mg/mL of LL-37. During the treatment period, the test product was applied every third day (±1 day), but not more often than twice a week. The test product was applied on the wound bed, using 25 µL solution per cm2 ulcer area, at concentrations 1.6 mg/mL of LL-37 and active doses of 40 µg/cm2.

    Reporting group title
    Placebo
    Reporting group description
    		 Patients were allocated to receive placebo (reference product). The placebo was applied every third day (±1 day), but not more often than twice a week. The ready-to-use reference product was applied on the wound bed, using 25 µL solution per cm2 ulcer area. The product was applied in the centre of the ulcer using a 1 mL graded syringe and distributed over the entire ulcer area.
    Reporting group title
    LL37 0.5 mg/mL group
    Reporting group description
    		 -

    Reporting group title
    LL37 1.6 mg/mL group
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Subject analysis set title
    Safety analysis set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Safety analysis set was defined as all patients who received at least one application of the study treatment. Analysis on the safety analysis set was based on actual treatment (i.e. patients were analysed “as treated”).

    Subject analysis set title
    Per-protocol analysis set
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per-protocol analysis set (PPAS) was defined as the subset of patients in the FAS who completed the treatment period and for whom no protocol deviation judged as having an impact on the primary efficacy analysis was reported or identified. The decision as to which protocol deviations were considered as reason for exclusion from the PPAS was made at the clean file meeting and documented in the clean file report. Analysis on the PPAS was based on the actual treatment (i.e. patients were analysed “as treated”).

    Subject analysis set title
    Full analysis set
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Full analysis set (FAS) was defined as all randomised patients who received at least one application of the study treatment and for whom at least one post-baseline ulcer assessment was made. Patients who were randomised in violation of eligibility criteria were excluded from the FAS. The blinding ensured that the decision of whether to begin treatment could not be influenced by knowledge of the assigned treatment, and thus the intention-to-treat principle was preserved despite the exclusion of patients who did not receive any application of the study treatment. The same rationale applied to the exclusion of patients with no post-baseline ulcer assessment, since the first such assessment was performed within a few days after baseline. Analysis on the FAS was based on the planned treatment (i.e. patients were analysed “as randomised”).

    Subject analysis set title
    FAS, sub-group of patients who completed the treatment period
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    FAS, sub-group of patients who completed the treatment period

    Subject analysis set title
    FAS, patients with wound area < 10 cm² at randomisation
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    FAS, patients with wound area < 10 cm² at randomisation

    Subject analysis set title
    FAS, patients with wound area ≥ 10 cm² at randomisation
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    FAS, patients with wound area ≥ 10 cm² at randomisation

    Primary: Confirmed complete wound closure of the target ulcer-estimated proportion of responders (FAS)

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer-estimated proportion of responders (FAS)
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. The wound closure was always to be documented by photography, both when first recorded and when confirmed 2 weeks later. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed. Post-wound closure visits could be conducted at any time point during the treatment period after the wound was assessed as closed. Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Primary
    End point timeframe
    Results presented are from data collected from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [1]
    48 [2]
    50 [3]
    Units: percentage
    number (confidence interval 90%)
        Estimated proportion of subjects (%)
    26.5 (17.1 to 38.7)
    24.7 (15.8 to 36.4)
    25.3 (16.4 to 36.9)
    Notes
    [1] - FAS
    [2] - FAS
    [3] - FAS
    Statistical analysis title
    		 Confirmed complete wound closure. FAS
    Statistical analysis description
    The primary efficacy variable, confirmed complete wound closure, was analysed using a logistic regression model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For dichotomous efficacy variables, the missing equals failure approach was used for the analysis on the FAS, i.e. patients with missing values were considered as non-responders.
    Comparison groups
    LL37 1.6 mg/mL group v Placebo v LL37 0.5 mg/mL group
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [4]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [4] - LL37 0.5 mg/mL vs placebo: OR = 1.067 (95% CI: 0.492, -), p-value = 0.4453 LL37 1.6 mg/mL vs placebo: OR = 0.968 (95% CI: 0.446, -), p-value= 0.5274

    Primary: Confirmed complete wound closure of the target ulcer- observed proportion of responders (FAS)

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer- observed proportion of responders (FAS) [5]
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed. Post-wound closure visits could be conducted at any time point during the treatment period after the wound was assessed as closed. Note that the proportion of responders presented is the observed proportion in the study (i.e. number of responders divided by the total number of patients, for each treatment group).
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [6]
    48 [7]
    50 [8]
    Units: subjects
        Not achieved
    33
    35
    37
        Achieved
    13
    13
    13
    Notes
    [6] - FAS
    [7] - FAS
    [8] - FAS
    No statistical analyses for this end point

    Primary: Confirmed complete wound closure of the target ulcer- estimated proportion of responders in the subgroup of patients that completed the treatment phase

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer- estimated proportion of responders in the subgroup of patients that completed the treatment phase
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. The wound closure was always to be documented by photography, both when first recorded and when confirmed 2 weeks later. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed. Post-wound closure visits could be conducted at any time point during the treatment period after the wound was assessed as closed. Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    42 [9]
    41 [10]
    48 [11]
    Units: percentage
    number (confidence interval 90%)
        Estimated proportion
    28.9 (18.7 to 41.9)
    29.5 (19.0 to 42.6)
    26.0 (16.8 to 38.0)
    Notes
    [9] - FAS, subgroup of patients who completed the treatment period
    [10] - FAS, subgroup of patients who completed the treatment period
    [11] - FAS, subgroup of patients who completed the treatment period
    Statistical analysis title
    		 Confirmed complete wound closure. Subgroup
    Statistical analysis description
    The primary efficacy variable, confirmed complete wound closure, was analysed using a logistic regression model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For dichotomous efficacy variables, the missing equals failure approach was used for the analysis on the FAS, i.e. patients with missing values were considered as non-responders.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [12]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [12] - LL37 0.5 mg/mL vs placebo: OR = 1.159 (0.527, -) , p-value = 0.3787 LL37 1.6 mg/mL vs placebo: OR = 1.189 (0.538, -), p-value = 0.3599

    Primary: Confirmed complete wound closure of the target ulcer- observed proportion of responders in the subgroup of patients that completed the treatment phase

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer- observed proportion of responders in the subgroup of patients that completed the treatment phase [13]
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed. Post-wound closure visits could be conducted at any time point during the treatment period after the wound was assessed as closed. Note that the proportion of responders presented is the observed proportion in the study (i.e. number of responders divided by the total number of patients, for each treatment group).
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    42 [14]
    41 [15]
    48 [16]
    Units: subjects
        Not achieved
    29
    28
    25
        Achieved
    13
    13
    13
    Notes
    [14] - FAS, subgroup of patients who completed the treatment period
    [15] - FAS, subgroup of patients who completed the treatment period
    [16] - FAS, subgroup of patients who completed the treatment period
    No statistical analyses for this end point

    Primary: Confirmed complete wound closure of the target ulcer- estimated proportion of responders (PPAS)

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer- estimated proportion of responders (PPAS) [17]
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. The wound closure was always to be documented by photography, both when first recorded and when confirmed 2 weeks later. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed. Post-wound closure visits could be conducted at any time point during the treatment period after the wound was assessed as closed. Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    Notes
    [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: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 Placebo LL37 0.5 mg/mL group LL37 1.6 mg/mL group
    Number of subjects analysed
    41 [18]
    41 [19]
    47 [20]
    Units: percentage
    number (confidence interval 90%)
        Estimated proportion
    29.8 (19.3 to 43.0)
    29.3 (18.9 to 42.4)
    26.6 (17.2 to 38.8)
    Notes
    [18] - PPAS
    [19] - PPAS
    [20] - PPAS
    Statistical analysis title
    		 Confirmed complete wound closure. PPAS
    Statistical analysis description
    The primary efficacy variable, confirmed complete wound closure, was analysed using a logistic regression model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For dichotomous efficacy variables, the missing equals failure approach was used for the analysis on the FAS, i.e. patients with missing values were considered as non-responders.
    Comparison groups
    Placebo v LL37 0.5 mg/mL group v LL37 1.6 mg/mL group
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [21]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [21] - LL37 0.5 mg/mL vs placebo: OR = 1.168 (0.528, -), p-value = 0.3735 LL37 1.6 mg/mL vs placebo: OR = 1.140 (0.514, -), p-value = 0.3933

    Primary: Confirmed complete wound closure of the target ulcer- observed proportion of responders (PPAS)

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer- observed proportion of responders (PPAS) [22]
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed. Post-wound closure visits could be conducted at any time point during the treatment period after the wound was assessed as closed. Note that the proportion of responders presented is the observed proportion in the study (i.e. number of responders divided by the total number of patients, for each treatment group).
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    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: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    41 [23]
    41 [24]
    47 [25]
    Units: subjects
        Not achieved
    28
    28
    34
        Achieved
    13
    13
    13
    Notes
    [23] - PPAS
    [24] - PPAS
    [25] - PPAS
    No statistical analyses for this end point

    Primary: Unconfirmed complete wound closure (FAS)

    		 Close Top of page
    End point title
    		 Unconfirmed complete wound closure (FAS) [26]
    End point description
    The number of patients who achieved complete wound closure during the treatment period but for whom the wound closure status was not possible to assess at the post-wound closure visit after 2 weeks (i.e. for whom it is not known whether the wound reopened or remained closed).
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    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: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [27]
    48 [28]
    50 [29]
    Units: subjects
        Wound closure
    15
    13
    15
        Unconfirmed closure
    2
    0
    1
    Notes
    [27] - FAS
    [28] - FAS
    [29] - FAS
    No statistical analyses for this end point

    Primary: Unconfirmed complete wound closure in the subgroup of patients who completed the treatment period

    		 Close Top of page
    End point title
    		 Unconfirmed complete wound closure in the subgroup of patients who completed the treatment period [30]
    End point description
    The number of patients who achieved complete wound closure during the treatment period but for whom the wound closure status was not possible to assess at the post-wound closure visit after 2 weeks (i.e. for whom it is not known whether the wound reopened or remained closed)
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    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: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    42 [31]
    41 [32]
    48 [33]
    Units: subjects
        Wound closure
    14
    13
    15
        Unconfirmed closure
    1
    0
    1
    Notes
    [31] - FAS, subgroup of patients who completed the treatment period
    [32] - FAS, subgroup of patients who completed the treatment period
    [33] - FAS, subgroup of patients who completed the treatment period
    No statistical analyses for this end point

    Primary: Unconfirmed complete wound closure (PPAS)

    		 Close Top of page
    End point title
    		 Unconfirmed complete wound closure (PPAS) [34]
    End point description
    The number of patients who achieved complete wound closure during the treatment period but for whom the wound closure status was not possible to assess at the post-wound closure visit after 2 weeks (i.e. for whom it is not known whether the wound reopened or remained closed)
    End point type
    Primary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    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: No statistical analysis was performed for this endpoint. Data is presented descriptively.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    41 [35]
    41 [36]
    47 [37]
    Units: subjects
        Wound closure
    13
    13
    14
        Unconfirmed wound closure
    0
    0
    0
    Notes
    [35] - PPAS
    [36] - PPAS
    [37] - PPAS
    No statistical analyses for this end point

    Secondary: Wound healing rate of the target ulcer, FAS

    		 Close Top of page
    End point title
    		 Wound healing rate of the target ulcer, FAS
    End point description
    The wound healing rate for each patient was estimated by fitting an exponential decay model with 2 parameters to the wound area measurements over time. Only wound area measurements during the treatment period (including the baseline measurement at randomisation) were considered for the modelling. For patients for whom the wound reopened after complete wound closure, only measurements up to and including the first time of wound closure were included in the model. Patients with less than 4 measurements were excluded from the analysis. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period).
    End point type
    Secondary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    42 [38]
    42 [39]
    48 [40]
    Units: rate
    arithmetic mean (confidence interval 90%)
        Wound healing rate
    0.0261 (0.0146 to 0.0375)
    0.0112 (-0.003 to 0.0227)
    0.0204 (0.0097 to 0.0312)
    Notes
    [38] - FAS
    [39] - FAS
    [40] - FAS
    Statistical analysis title
    		 Wound healing rate difference
    Statistical analysis description
    The wound healing rate was analysed using an analysis of covariance (ANCOVA) model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. Each active treatment group was tested against placebo, and the null hypotheses that the least square mean difference in wound healing rate is equal to zero were tested against one-sided alternative hypotheses that the difference ≥ 0.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    132
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [41]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Confidence interval
    Notes
    [41] - LL37 0.5 mg/mL vs placebo: difference in wound healing rate = 0.0057/day (95% CI: -0.0100, -), p-value = 0.2759 LL37 1.6 mg/mL vs placebo: difference in wound healing rate = -0.0092/day (95% CI: -0.0250, -) , p-value = 0.8326

    Secondary: Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS

    		 Close Top of page
    End point title
    		 Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS
    End point description
    Time to confirmed complete wound closure was analysed using a regression analysis to estimate the restricted mean survival time (RMST). The model included treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For patients completing the treatment period or being prematurely withdrawn from the study without experiencing confirmed complete wound closure (including patients for whom the wound reopened during the post-wound closure visits), the time to event was right-censored at the date of end of treatment/ withdrawal.
    End point type
    Secondary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [42]
    48 [43]
    50 [44]
    Units: days
    arithmetic mean (confidence interval 90%)
        RMST
    83.1 (76.3 to 89.8)
    90.3 (86.2 to 94.3)
    87.9 (83.3 to 92.6)
    Notes
    [42] - FAS
    [43] - FAS
    [44] - FAS
    Statistical analysis title
    		 Difference in RMST (FAS)
    Statistical analysis description
    Each of the two active treatment groups were tested separately against placebo, and null hypotheses that the difference in RMST for confirmed complete wound closure is equal to zero were tested against one-sided alternative hypotheses that the difference in RMST is less than zero.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [45]
    Method
    		 RMST regression
    Parameter type
    		 RMST difference
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [45] - LL37 0.5 mg/mL vs placebo: difference in RMST = -4.9 (-, 3.3), p-value = 0.1644 LL37 1.6 mg/mL vs placebo: difference in RMST = 2.3 (-, 8.7), p-value = 0.7270

    Secondary: Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS, subgroup of patients who completed the treatment period

    		 Close Top of page
    End point title
    		 Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS, subgroup of patients who completed the treatment period
    End point description
    Time to confirmed complete wound closure was analysed using a regression analysis to estimate the restricted mean survival time (RMST). The model included treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For patients completing the treatment period or being prematurely withdrawn from the study without experiencing confirmed complete wound closure (including patients for whom the wound reopened during the post-wound closure visits), the time to event was right-censored at the date of end of treatment/ withdrawal.
    End point type
    Secondary
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    42 [46]
    41 [47]
    48 [48]
    Units: days
    arithmetic mean (confidence interval 90%)
        RMST
    82.0 (74.9 to 89.1)
    89.6 (85.0 to 94.1)
    87.8 (83.1 to 92.5)
    Notes
    [46] - FAS, subgroup of patients who completed the treatment period
    [47] - FAS, subgroup of patients who completed the treatment period
    [48] - FAS, subgroup of patients who completed the treatment period
    Statistical analysis title
    		 Difference in RMST, FAS completed treatment
    Statistical analysis description
    Each of the two active treatment groups were tested separately against placebo, and null hypotheses that the difference in RMST for confirmed complete wound closure is equal to zero were tested against one-sided alternative hypotheses that the difference in RMST is less than zero.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [49]
    Method
    		 RMST regression
    Parameter type
    		 RMST difference
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [49] - LL37 0.5 mg/mL vs placebo: difference in RMST = -5.8 (-, 2.8), p-value = 0.1348 LL37 1.6 mg/mL vs placebo: difference in RMST = 1.8 (-, 8.4) p-value = 0.6677

    Secondary: Attainment of target ulcer area reduction of at least 50% from baseline-estimated proportion of responders (FAS)

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 50% from baseline-estimated proportion of responders (FAS)
    End point description
    Attainment of target ulcer area reduction of at least 50% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period). Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Secondary
    End point timeframe
    Endpoint was asseesd at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [50]
    48 [51]
    50 [52]
    Units: percentage
    arithmetic mean (confidence interval 90%)
        Estimated proportion of reposnders
    56.4 (44.2 to 67.8)
    35.0 (24.6 to 47.0)
    46.2 (34.9 to 57.9)
    Notes
    [50] - FAS
    [51] - FAS
    [52] - FAS
    Statistical analysis title
    		 Attainment ≥ 50%, OR vs placebo (FAS)
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the target ulcer (dichotomised as < or ≥ 10cm²) and duration of the target ulcer at baseline.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [53]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [53] - LL37 0.5 mg/mL vs placebo: OR = 1.507 (0.764, -), p-value = 0.1603 LL37 1.6 mg/mL vs placebo: OR = 0.627 (0.314, -) , p-value = 0.8666

    Secondary: Attainment of target ulcer area reduction of at least 70% from baseline-estimated proportion of responders (FAS)

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 70% from baseline-estimated proportion of responders (FAS)
    End point description
    Attainment of target ulcer area reduction of at least 70% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period). Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Secondary
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [54]
    48 [55]
    50 [56]
    Units: percentage
    arithmetic mean (confidence interval 90%)
        Estimated proportion of responders
    43.1 (31.6 to 55.3)
    34.6 (24.2 to 46.6)
    34.0 (23.9 to 45.9)
    Notes
    [54] - FAS
    [55] - FAS
    [56] - FAS
    Statistical analysis title
    		 Attainment ≥ 70%, OR vs placebo (FAS)
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the target ulcer (dichotomised as < or ≥ 10cm²) and duration of the target ulcer at baseline.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [57]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [57] - LL37 0.5 mg/mL vs placebo: OR =1.465 (0.729, —) , p-value = 0.1839 LL37 1.6 mg/mL vs placebo: OR = 1.023 (0.503, —), p-value = 0.4788

    Secondary: Attainment of target ulcer area reduction of at least 50% from baseline- Number of patients that achieved it or not (FAS)

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 50% from baseline- Number of patients that achieved it or not (FAS)
    End point description
    Attainment of target ulcer area reduction of at least 50% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period).
    End point type
    Secondary
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [58]
    48 [59]
    50 [60]
    Units: subjects
        Achieved
    26
    17
    23
        Not achieved
    20
    31
    27
        Missing
    3
    4
    3
    Notes
    [58] - FAS
    [59] - FAS
    [60] - FAS
    No statistical analyses for this end point

    Secondary: Attainment of target ulcer area reduction of at least 70% from baseline- Number of patients that achieved it or not (FAS)

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 70% from baseline- Number of patients that achieved it or not (FAS)
    End point description
    Attainment of target ulcer area reduction of at least 70% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period).
    End point type
    Secondary
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    46 [61]
    48 [62]
    50 [63]
    Units: subjects
        Achieved
    20
    17
    17
        Not achieved
    26
    31
    33
        Missing
    3
    4
    3
    Notes
    [61] - FAS
    [62] - FAS
    [63] - FAS
    No statistical analyses for this end point

    Post-hoc: Confirmed complete wound closure. FAS, subgroup of patients with wound area less than 10 cm² at randomisation.

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure. FAS, subgroup of patients with wound area less than 10 cm² at randomisation.
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. The wound closure was always to be documented by photography, both when first recorded and when confirmed 2 weeks later. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed.
    End point type
    Post-hoc
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    25 [64]
    27 [65]
    26 [66]
    Units: percentage
    number (confidence interval 90%)
        Estimated proportion
    26.0 (14.1 to 42.8)
    31.4 (18.7 to 47.7)
    44.2 (28.8 to 60.8)
    Notes
    [64] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [65] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [66] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    Statistical analysis title
    		 Confirmed complete wound closure. Subgroup
    Statistical analysis description
    The primary efficacy variable, confirmed complete wound closure, was analysed using a logistic regression model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For dichotomous efficacy variables, the missing equals failure approach was used for the analysis on the FAS, i.e. patients with missing values were considered as non-responders.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [67]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [67] - LL37 0.5 mg/mL vs placebo: OR = 0.443 (0.160, -), p-value = 0.9062 LL37 1.6 mg/mL vs placebo: OR = 0.578 (0.220, -), p-value = 0.8252

    Post-hoc: Confirmed complete wound closure of the target ulcer. FAS, subgroup of patients with wound area at least 10 cm² at randomisation.

    		 Close Top of page
    End point title
    		 Confirmed complete wound closure of the target ulcer. FAS, subgroup of patients with wound area at least 10 cm² at randomisation.
    End point description
    The primary efficacy endpoint was a confirmed complete wound closure of the target ulcer, defined as skin re-epithelialisation without drainage or dressing requirements at any time up to the end-of-treatment visit at 13 weeks, which was sustained at the post-wound closure visit, 2 weeks after the first reported closure. The Investigator assessed at each visit whether complete wound closure of the target ulcer had been achieved. The wound closure was always to be documented by photography, both when first recorded and when confirmed 2 weeks later. At the post-wound closure visits, 2 weeks after the complete wound closure was first reported, the Investigator assessed whether the complete wound closure was confirmed.
    End point type
    Post-hoc
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    21 [68]
    21 [69]
    24 [70]
    Units: percentage
        number (confidence interval 90%)
    28.1 (14.9 to 46.6)
    19.6 (8.8 to 38.0)
    8.1 (2.5 to 23.1)
    Notes
    [68] - FAS, patients with wound area ≥ 10 cm² at randomisation
    [69] - FAS, patients with wound area ≥ 10 cm² at randomisation
    [70] - FAS, patients with wound area ≥ 10 cm² at randomisation
    Statistical analysis title
    		 Confirmed complete wound closure. Subgroup
    Statistical analysis description
    The primary efficacy variable, confirmed complete wound closure, was analysed using a logistic regression model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For dichotomous efficacy variables, the missing equals failure approach was used for the analysis on the FAS, i.e. patients with missing values were considered as non-responders.
    Comparison groups
    LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    45
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [71]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [71] - LL37 1.6 mg/mL vs placebo: OR = 2.771 (0.590, -), p-value = 0.1393
    Statistical analysis title
    		 Confirmed complete wound closure. Subgroup
    Statistical analysis description
    The primary efficacy variable, confirmed complete wound closure, was analysed using a logistic regression model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For dichotomous efficacy variables, the missing equals failure approach was used for the analysis on the FAS, i.e. patients with missing values were considered as non-responders.
    Comparison groups
    Placebo v LL37 0.5 mg/mL group
    Number of subjects included in analysis
    45
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [72]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [72] - LL37 0.5 mg/mL vs placebo: OR = 4.454 (1.038, -), p-value = 0.0458

    Post-hoc: Wound healing rate. FAS, subgroup of patients with wound area less than 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Wound healing rate. FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    End point description
    The wound healing rate for each patient was estimated by fitting an exponential decay model with 2 parameters to the wound area measurements over time. Only wound area measurements during the treatment period (including the baseline measurement at randomisation) were considered for the modelling. For patients for whom the wound reopened after complete wound closure, only measurements up to and including the first time of wound closure were included in the model. Patients with less than 4 measurements were excluded from the analysis. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period).
    End point type
    Post-hoc
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    21 [73]
    22 [74]
    24 [75]
    Units: rate
    arithmetic mean (confidence interval 90%)
        Wound healing rate
    0.0138 (0.0020 to 0.0256)
    0.0076 (-0.0040 to 0.0191)
    0.0324 (0.0213 to 0.0435)
    Notes
    [73] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [74] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [75] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    Statistical analysis title
    		 Wound healing rate difference (subgroup analysis)
    Statistical analysis description
    The wound healing rate was analysed using an analysis of covariance (ANCOVA) model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. Each active treatment group was tested against placebo, and the null hypotheses that the least square mean difference in wound healing rate is equal to zero were tested against one-sided alternative hypotheses that the difference ≥ 0.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    67
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [76]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Confidence interval
    Notes
    [76] - LL37 0.5 mg/mL vs placebo: difference in wound healing rate = -0.0186/day (95% CI: -0.0348, -) , p-value = 0.9693 LL37 1.6 mg/mL vs placebo: difference in wound healing rate = -0.0248/day (95% CI: -0.0409, -) , p-value = 0.9939

    Post-hoc: Wound healing rate. FAS, subgroup of patients with wound area at least 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Wound healing rate. FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    End point description
    The wound healing rate for each patient was estimated by fitting an exponential decay model with 2 parameters to the wound area measurements over time. Only wound area measurements during the treatment period (including the baseline measurement at randomisation) were considered for the modelling. For patients for whom the wound reopened after complete wound closure, only measurements up to and including the first time of wound closure were included in the model. Patients with less than 4 measurements were excluded from the analysis. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period).
    End point type
    Post-hoc
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    21 [77]
    20 [78]
    24 [79]
    Units: rate
    arithmetic mean (confidence interval 90%)
        Wound rate
    0.0367 (0.0174 to 0.0559)
    0.0159 (-0.0040 to 0.0358)
    0.0093 (-0.0087 to 0.0274)
    Notes
    [77] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [78] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [79] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    Statistical analysis title
    		 Wound healing rate difference (subgroup analysis)
    Statistical analysis description
    The wound healing rate was analysed using an analysis of covariance (ANCOVA) model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. Each active treatment group was tested against placebo, and the null hypotheses that the least square mean difference in wound healing rate is equal to zero were tested against one-sided alternative hypotheses that the difference ≥ 0.
    Comparison groups
    LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [80]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Confidence interval
    Notes
    [80] - LL37 1.6 mg/mL vs placebo: difference in wound healing rate = 0.0066 (95% CI: -0.0204, -) , p-value = 0.3430
    Statistical analysis title
    		 Wound healing rate difference (subgroup...
    Statistical analysis description
    The wound healing rate was analysed using an analysis of covariance (ANCOVA) model, including treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. Each active treatment group was tested against placebo, and the null hypotheses that the least square mean difference in wound healing rate is equal to zero were tested against one-sided alternative hypotheses that the difference ≥ 0.
    Comparison groups
    Placebo v LL37 0.5 mg/mL group
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [81]
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Confidence interval
    Notes
    [81] - LL37 0.5 mg/mL vs placebo: OR = 3.252 (1.165, -) , p-value = 0.0294

    Post-hoc: Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS, subgroup of patients with wound area less than 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    End point description
    Time to confirmed complete wound closure was analysed using a regression analysis to estimate the restricted mean survival time (RMST). The model included treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For patients completing the treatment period or being prematurely withdrawn from the study without experiencing confirmed complete wound closure (including patients for whom the wound reopened during the post-wound closure visits), the time to event was right-censored at the date of end of treatment/ withdrawal.
    End point type
    Post-hoc
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    25 [82]
    27 [83]
    26 [84]
    Units: days
    arithmetic mean (confidence interval 90%)
        RMST
    77.9 (67.4 to 88.4)
    86.1 (80.1 to 92.2)
    77.2 (68.8 to 85.9)
    Notes
    [82] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [83] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [84] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    Statistical analysis title
    		 Difference in RMST, FAS subgroup analysis
    Statistical analysis description
    Each of the two active treatment groups were tested separately against placebo, and null hypotheses that the difference in RMST for confirmed complete wound closure is equal to zero were tested against one-sided alternative hypotheses that the difference in RMST is less than zero.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [85]
    Method
    		 RMST regression
    Parameter type
    		 RMST difference
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [85] - LL37 0.5 mg/mL vs placebo: difference in RMST = 0.7 (-, 14.1), p-value = 0.5333 LL37 1.6 mg/mL vs placebo: difference in RMST = 0,8.9 (-, 19.4) p-value = 0.9181

    Post-hoc: Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS, subgroup of patients with wound area at least 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Time to confirmed complete wound closure- restricted mean survival time (RMST). FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    End point description
    Time to confirmed complete wound closure was analysed using a regression analysis to estimate the restricted mean survival time (RMST). The model included treatment group and the baseline area of the target ulcer (dichotomous stratification factor) as factors, and the duration of the target ulcer at baseline as a covariate. For patients completing the treatment period or being prematurely withdrawn from the study without experiencing confirmed complete wound closure (including patients for whom the wound reopened during the post-wound closure visits), the time to event was right-censored at the date of end of treatment/ withdrawal.
    End point type
    Post-hoc
    End point timeframe
    Results presented are from data collected during the study, from the start of the run-in period to the end of post-wound closure period at Visit 36 (Week 15). No efficacy evaluation was performed during the follow-up period.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    21 [86]
    21 [87]
    24 [88]
    Units: days
    arithmetic mean (confidence interval 90%)
        RMST
    87.4 (80.9 to 93.9)
    92.6 (88.3 to 96.9)
    97.5 (96.1 to 98.8)
    Notes
    [86] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [87] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [88] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    Statistical analysis title
    		 Difference in RMST, FAS subgroup analysis
    Statistical analysis description
    Each of the two active treatment groups were tested separately against placebo, and null hypotheses that the difference in RMST for confirmed complete wound closure is equal to zero were tested against one-sided alternative hypotheses that the difference in RMST is less than zero.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [89]
    Method
    		 RMST regression
    Parameter type
    		 RMST difference
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [89] - LL37 0.5 mg/mL vs placebo: difference in RMST = -10.1 (-, -3.4), p-value = 0.0066 LL37 1.6 mg/mL vs placebo: difference in RMST = -4.8 (-, 0.3),- p-value = 0.0407

    Post-hoc: Attainment of target ulcer area reduction of at least 50% from baseline-estimated proportion of responders. FAS, subgroup of patients with wound area less than 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 50% from baseline-estimated proportion of responders. FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    End point description
    Attainment of target ulcer area reduction of at least 50% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period). Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Post-hoc
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    25 [90]
    27 [91]
    26 [92]
    Units: percentage
    arithmetic mean (confidence interval 90%)
        Estimated proportion of responders
    51.6 (35.4 to 67.4)
    32.8 (19.9 to 49.0)
    58.7 (42.2 to 73.4)
    Notes
    [90] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [91] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [92] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    Statistical analysis title
    		 Attainment ≥ 50% OR vs placebo (subgroup analysis)
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the target ulcer (dichotomised as < or ≥ 10cm²) and duration of the target ulcer at baseline.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [93]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [93] - LL37 0.5 mg/mL vs placebo: OR = 0.750 (0.292, -), p-value = 0.6920 LL37 1.6 mg/mL vs placebo: OR = 0.344 (0.133, -), p-value = 0.9669

    Post-hoc: Attainment of target ulcer area reduction of at least 50% from baseline-estimated proportion of responders. FAS, subgroup of patients with wound area at least 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 50% from baseline-estimated proportion of responders. FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    End point description
    Attainment of target ulcer area reduction of at least 50% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period). Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Post-hoc
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    21 [94]
    21 [95]
    24 [96]
    Units: percentage
    arithmetic mean (confidence interval 90%)
        Estimated proportion of responders
    61.9 (43.6 to 77.3)
    38.2 (22.7 to 56.6)
    33.3 (19.6 to 50.5)
    Notes
    [94] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [95] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [96] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    Statistical analysis title
    		 Attainment ≥ 50% OR vs placebo (subgroup analysis)
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the target ulcer (dichotomised as < or ≥ 10cm²) and duration of the target ulcer at baseline.
    Comparison groups
    LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05 [97]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [97] - LL37 1.6 mg/mL vs placebo: OR = 1.240 (0.438, ), p-value = 0.3669
    Statistical analysis title
    		 Attainment ≥ 50% OR vs placebo (subgrou...
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the target ulcer (dichotomised as < or ≥ 10cm²) and duration of the target ulcer at baseline.
    Comparison groups
    Placebo v LL37 0.5 mg/mL group
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [98]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [98] - LL37 0.5 mg/mL vs placebo: OR = 3.252 (1.165, -) , p-value = 0.0294

    Post-hoc: Attainment of target ulcer area reduction of at least 70% from baseline-estimated proportion of responders FAS, subgroup of patients with wound area less than 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 70% from baseline-estimated proportion of responders FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    End point description
    Attainment of target ulcer area reduction of at least 70% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period). Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Post-hoc
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    25 [99]
    27 [100]
    26 [101]
    Units: percentage
    arithmetic mean (confidence interval 90%)
        Estimated proportion of responders
    38.7 (24.2 to 55.6)
    32.1 (19.3 to 48.3)
    51.9 (35.8 to 67.7)
    Notes
    [99] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [100] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    [101] - FAS, subgroup of patients with wound area less than 10 cm² at randomisation
    Statistical analysis title
    		 Attainment ≥ 70% OR vs placebo (subgroup analysis)
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the target ulcer (dichotomised as < or ≥ 10cm²) and duration of the target ulcer at baseline.
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    78
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [102]
    P-value
    		 > 0.05 [103]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 90%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [102] - One-sided tests of differences from placebo were performed for each of the two active treatment groups at the 0.05 significance level.
    [103] - LL37 0.5 mg/mL vs placebo: OR = 0.586 (0.224, -), p-value = 0.8205 LL37 1.6 mg/mL vs placebo: OR = 0.438 (0.168, -), p-value = 0.9223

    Post-hoc: Attainment of target ulcer area reduction of at least 70% from baseline-estimated proportion of responders. FAS, subgroup of patients with wound area at least 10 cm² at randomisation

    		 Close Top of page
    End point title
    		 Attainment of target ulcer area reduction of at least 70% from baseline-estimated proportion of responders. FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    End point description
    Attainment of target ulcer area reduction of at least 70% at end-of-treatment compared to baseline was analysed using logistic regression models. Wound area measurements were performed at Visits 1, 3 and 6 (Run-in period), Visits 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 (Treatment period) and at Visits 37 and 38 (follow-up period). Wound photography was performed at the same timepoints and at Visits 34 and 36 (post-wound closure period). Note that the estimated proportion of responders is based on the statistical model (logistic regression analysis) and adjusted for covariates.
    End point type
    Post-hoc
    End point timeframe
    Endpoint was assessed at the end of the treatment period and compared to the baseline.
    End point values
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Number of subjects analysed
    21 [104]
    21 [105]
    24 [106]
    Units: percentage
    arithmetic mean (confidence interval 90%)
        Estimated proportion of responders
    47.2 (30.3 to 64.8)
    39.0 (23.3 to 57.5)
    16.2 (7.2 to 32.5)
    Notes
    [104] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [105] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    [106] - FAS, subgroup of patients with wound area at least 10 cm² at randomisation
    Statistical analysis title
    		 Attainment ≥ 70%,OR vs placebo (subgroup analysis)
    Statistical analysis description
    A logistic regression model was used. The model was adjusted for treatment, baseline area of the
    Comparison groups
    LL37 0.5 mg/mL group v LL37 1.6 mg/mL group v Placebo
    Number of subjects included in analysis
    66
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05 [107]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 -
         upper limit
    		 -
    Notes
    [107] - LL37 0.5 mg/mL vs placebo: OR = 4.619 (1.450, -) , p-value = 0.0149 LL37 1.6 mg/mL vs placebo: OR = 3.307 (1.005, -), p-value = 0.0493

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Total study: Screening and run-in period (Visits 1 to 6, Weeks -3 to -1) Treatment period (Visits 7 to 32, Weeks 1 to 13) Post-wound closure period (Visits 33 to 36, Weeks 14 to 15) Follow-up period (Visits 37 and 38, Weeks 21 and 29)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    LL37 0.5 mg/mL group
    Reporting group description
    		 -

    Reporting group title
    LL37 1.6 mg/mL group
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 48 (8.33%)
    6 / 49 (12.24%)
    1 / 51 (1.96%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 48 (2.08%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 48 (0.00%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 48 (0.00%)
    0 / 49 (0.00%)
    1 / 51 (1.96%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    1 / 48 (2.08%)
    1 / 49 (2.04%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 48 (2.08%)
    0 / 49 (0.00%)
    0 / 51 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 LL37 0.5 mg/mL group LL37 1.6 mg/mL group Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 48 (31.25%)
    14 / 49 (28.57%)
    10 / 51 (19.61%)
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    6 / 48 (12.50%)
    4 / 49 (8.16%)
    3 / 51 (5.88%)
         occurrences all number
    15
    9
    5
    Underdose
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    1 / 51 (1.96%)
         occurrences all number
    5
    5
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 48 (4.17%)
    2 / 49 (4.08%)
    3 / 51 (5.88%)
         occurrences all number
    2
    2
    3
    Infections and infestations
    Wound infection
         subjects affected / exposed
    3 / 48 (6.25%)
    2 / 49 (4.08%)
    3 / 51 (5.88%)
         occurrences all number
    4
    2
    3
    Erysipelas
         subjects affected / exposed
    2 / 48 (4.17%)
    3 / 49 (6.12%)
    0 / 51 (0.00%)
         occurrences all number
    4
    5
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Sep 2018
    The first CSP version under which patients were included in the study was version 1.0 (dated 2018 03-01). After this, there was one protocol amendment in the study, resulting in CSP version 2.0 (dated 2018 06-11). Changes included sample time point correction, clarification of description of blinding and unblinding, as well as clarification that patients with missing data should be considered as non-responders in the main analysis on the full analysis set, upon request from the Swedish competent authorities.

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

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

    European Medicines Agency © 1995-Sat Sep 21 03:05:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA