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    Clinical Trial Results:
    Effect of topical rhGM-CSF on the healing of venous leg ulcers: a randomized, placebo-controlled, double-blind, clinical phase II study

    Summary
    EudraCT number
    		 2019-001483-30
    Trial protocol
    		 DK  
    Global end of trial date
    30 Jan 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Feb 2026
    First version publication date
    15 Feb 2026
    Other versions
    Summary report(s)
    		 Synopsis of study results_Repogel-01

    Trial information

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    Trial identification
    Sponsor protocol code
    BBH-GMCSF-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Reponex Pharmaceuticals A/S
    Sponsor organisation address
    Slotsmarken 12, 1.th. , Hørsholm, Denmark,
    Public contact
    Reponex Pharmaceuticals A/S, Reponex Pharmaceuticals A/S, vp@reponex.dk
    Scientific contact
    Reponex Pharmaceuticals A/S, Reponex Pharmaceuticals A/S, vp@reponex.dk
    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
    22 Jan 2026
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Jan 2025
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jan 2025
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To study the effect of rhGM-CSF on ulcer size reduction, when applied directly in the wound bed of difficult-to-heal venous leg ulcers, given on top of standard care. This was evaluated by measuring the ulcer area change after 4 weeks of treatment compared to placebo.
    Protection of trial subjects
    For safety reasons, the study drug /placebo was applied in the outpatient wound clinic at the hospital with close monitoring of pain and immediate adverse events. During the treatment period with the study drug/placebo participants also received standard care by highly experienced wound care nurses a the center. Participants were compensated for traveling expenses in accordance with the reimbursement policy. Analgesics were offered in the case of pain.
    Background therapy
    		 The following standard of care was performed twice a week in all participants (placebo/Repogel): 1. Ulcer debridement: mechanical or sharp debridement e.g. with a curette, performed at each visit, unless the procedure was too painful. 2. Ulcer irrigation: performed at every study visit with clean tap water 3. Dressing: Ulcers were dressed with a neutral non-medicated dressing at each visit accord-ing to the clinical routine in the department, reflecting the stage and needs of the individual wound. A preference list of dressing choices were made before inclusion. Active dressings such as silver-impregnated dressings or dressings with ibuprofen were not allowed. Dressing type was registered in the eCRF. 4. Compression therapy: Bandages with Coban 2TM, 3MTM were used. CobanTM (“Coban I”) was also accepted 5. Periwound skin treatment: The use of moisturizing creams and protecting the wound bor-der from maceration were used if clinically indicated Home nurse visits: Some of the dressing changes were performed by the home care nurses or at nurses’ clinics in the follow-up period (in accordance with clinical routines).
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Apr 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 6
    Worldwide total number of subjects
    6
    EEA total number of subjects
    6
    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)
    2
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was conducted at the Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital, Denmark. The first patient was randomized 13-04-2021 and the last patient finished the study 19-10-2021.

    Pre-assignment
    Screening details
    		 The target population consisted of adult patients suffering from difficult-to-heal venous leg ulcers, with an ulcer duration of ≥2 months and ≤3 years and an ulcer size 2-75 cm2 at the randomization day.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 -
    Arm type
    		 Placebo

    Investigational medicinal product name
    Hydrogel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Gel
    Routes of administration
    Topical
    Dosage and administration details
    Twice weekly for 4 weeks topically in the wound bed

    Arm title
    		 Repogel
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Repogel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Gel
    Routes of administration
    Topical
    Dosage and administration details
    Repogel containing rhGM-CSF (molgramostim) in a hydrogel with an aimed concentration of 50 mikrgram molgramostim per mL of hydrogel. The treatment was adminstered locally in the wound bed twice weekly for 4 weeks with a dosage of 5 mikrogram/cm2 rhGM-CSF of wound bed. The ulcer area was calculated by means of Silhouette Star (Aranz medical) at every treatment visit, and the ulcer area at that visit determined the individual dose to be applied to the ulcer. The study drug/placebo was supplied in a transparent syringe of 10 mL, indicating the volume used. The maximal dosage of molgramostim that could be given at each administration was 375 mikrogram.

    Number of subjects in period 1
    		Placebo Repogel
    Started
    3
    3
    Completed
    3
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Repogel
    Reporting group description
    		 -

    Reporting group values
    		 Placebo Repogel Total
    Number of subjects
    		 3 3 6
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 1 1 2
        From 65-84 years
    		 2 2 4
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 73 (63.0 to 74.5) 67 (62.5 to 74.5) -
    Gender categorical
    Units: Subjects
        Female
    		 0 1 1
        Male
    		 3 2 5
    Ulcer duration
    Units: Months
        median (inter-quartile range (Q1-Q3))
    		 6 (4.0 to 7.7) 8 (5.5 to 11.0) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Repogel
    Reporting group description
    		 -

    Primary: Primary endpoint

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    End point title
    		 Primary endpoint
    End point description
    Proportion of patients reaching a 40% ulcer area reduction, or more, 4 weeks after initiation of the study drug treatment/placebo
    End point type
    Primary
    End point timeframe
    4 weeks after randomization
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: Number of subjects
        number (not applicable)
    1
    0
    Statistical analysis title
    		 No statistical analysis
    Statistical analysis description
    Too small sample size (n=6). For this reason, test of statistical significance was deemed as inappropriate.
    Comparison groups
    Repogel v Placebo
    Number of subjects included in analysis
    6
    Analysis specification
    Post-hoc
    Analysis type
    		 other [1]
    P-value
    		 ≤ 0.05 [2]
    Method
    		 No statistical testing
    Confidence interval
    Notes
    [1] - Too small sample size (n=6). For this reason, test of statistical significance was deemed as inappropriate.
    [2] - Originally planned

    Secondary: Absolute ulcer area change 4 weeks after randomization (cm2)

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    End point title
    		 Absolute ulcer area change 4 weeks after randomization (cm2)
    End point description
    End point type
    Secondary
    End point timeframe
    4 weeks after randomization
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: cm2
        arithmetic mean (standard deviation)
    4.5 ( 5.3 )
    -0.8 ( 1.6 )
    No statistical analyses for this end point

    Secondary: Absolute ulcer area change 8 weeks after randomization (cm2)

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    End point title
    		 Absolute ulcer area change 8 weeks after randomization (cm2)
    End point description
    End point type
    Secondary
    End point timeframe
    8 weeks after randomization
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: cm2
        arithmetic mean (standard deviation)
    6.3 ( 5.3 )
    -5.2 ( 8.0 )
    No statistical analyses for this end point

    Secondary: Percentage reduction of the ulcer area 4 weeks after randomization

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    End point title
    		 Percentage reduction of the ulcer area 4 weeks after randomization
    End point description
    A negative value indicates an increase in wound size
    End point type
    Secondary
    End point timeframe
    4 weeks after randomization
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: Percentage area reduction
        arithmetic mean (standard deviation)
    26.5 ( 33.7 )
    1.8 ( 10.5 )
    No statistical analyses for this end point

    Secondary: Percentage reduction of the ulcer area 8 weeks after randomization

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    End point title
    		 Percentage reduction of the ulcer area 8 weeks after randomization
    End point description
    A negative values indicates an increase in wound size
    End point type
    Secondary
    End point timeframe
    8 weeks after randomization
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: Percentage area reduction
        arithmetic mean (standard deviation)
    65 ( 20.1 )
    -10.5 ( 56.6 )
    No statistical analyses for this end point

    Secondary: Complete ulcer healing (full epithelialization and no drainage of wound fluid) 4 and 8 weeks after randomization

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    End point title
    		 Complete ulcer healing (full epithelialization and no drainage of wound fluid) 4 and 8 weeks after randomization
    End point description
    End point type
    Secondary
    End point timeframe
    4 and 8 weeks after randomization
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: Number of participants
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Time to complete ulcer healing

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    End point title
    		 Time to complete ulcer healing
    End point description
    No participant in any study group experienced complete ulcer healing
    End point type
    Secondary
    End point timeframe
    During study period
    End point values
    		 Placebo Repogel
    Number of subjects analysed
    3
    3
    Units: Number og subjects
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the screening visit to the end-of-trial visit.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 SNOMED CT
    Dictionary version
    2025-09-30
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 -

    Reporting group title
    Repogel
    Reporting group description
    		 -

    Serious adverse events
    		 Placebo Repogel
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Repogel
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    Cardiac disorders
    Hypertension
    Additional description: Worsening of hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Serology abnormal
    Additional description: Increasing alkaline phosphatase
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Wound
    Additional description: New wound (small) developed on index leg. Unknown cause.
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Wound infection bacterial
    Additional description: Wound infection (streptococci)
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    Wound complication
    Additional description: Worsening of wounds on index leg
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Dermatitis allergic
    Additional description: Allergic exanthema after a wound care product (not placebo/Repogel)
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Muscle discomfort
    Additional description: Muscular lumbar pain; participant slipped at work
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1
    Bursitis
    Additional description: Bursitis olcecrani, right arm
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    08 Nov 2021
    The current study was temporarily stopped by the Danish Medicines Agency 08. Nov. 2021, following an inspection at sponsors site, due to insufficient validation of the analysis methods of the study drug in the dosage form (Repogel) in batch BA055HBMH. rhGM-CSF in the hydrogel dosage form used in the study were shown as physically not stable due to the hypothesis of stress during manu-facturing process caused alteration of peptide chain over the time. As subjects were included sequentially and participating in the study over a 6-month period, the content of rhGM-CSF may have varied significantly between the patients. At this timepoint six patients were included in the study. With the necessary documentation, the study could be continued. Despite multiple attempts, it was observed that Repogel dosage form was not robust enough and quantification of rhGM-CSF was not reproducible. It was concluded that to achieve the necessary validation/documentation was not possible and therefore it was decided to stop the study and report on the six patients included. Finally a closure of the study was filed in January 2025 with the results of six patients only and without any statistically analysis due to very small sample size (n=6). A dose of 5 mikrogram of rhGM-CSF (molgramostim) per cm2 of wound bed was aimed at being used in the study. The study drug was administered twice a week for 4 consecutive weeks. The maximal dosage of molgramostim that could be given at each administration in our trial, 375 mikrogram.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    No firm conclusions about the efficacy and safety of rhGM-CSF can be drawn from this study due to insufficient data and very few number of enrolled patients (n=6).
    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
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