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Effect of rhGM-CSF on the Healing of Venous Leg Ulcers

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ClinicalTrials.gov Identifier: NCT04823962
Recruitment Status : Recruiting
First Posted : April 1, 2021
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Ewa Anna Burian, Reponex Pharmaceuticals A/S

Tracking Information
First Submitted Date  ICMJE March 6, 2021
First Posted Date  ICMJE April 1, 2021
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE March 11, 2021
Estimated Primary Completion Date May 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
Proportion of patients reaching a 40% ulcer area reduction, or more, 4 weeks after initiation of the study drug treatment/placebo [ Time Frame: 4 weeks after initiation of the study drug treatment/placebo ]
Ulcer size (area in cm2) will be assessed on the randomization day (Day 0; initiation of the study drug treatment/placebo) and at the end of the study drug/placebo treatment (D28+1)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Absolute change of the ulcer area [ Time Frame: 4 and 8 weeks after randomization ]
    The ulcer size is compared in terms of change in cm2 from the randomization day
  • Percentage change of the ulcer area [ Time Frame: 4 and 8 weeks after randomization ]
    The ulcer size is compared in terms of percentage change from the randomization day
  • Complete ulcer healing [ Time Frame: 4 and 8 weeks after randomization ]
    Number of subjects reaching complete ulcer healing; Full epithelization and no drainage of wound fluid or dressing requirements
  • Time to complete ulcer healing [ Time Frame: Through study completion (8 weeks) ]
    Time to complete ulcer healing in days, with the randomization day as baseline
  • Clinical improvement of the wound healing process [ Time Frame: 4 and 8 weeks after randomization ]
    Semi-quantitatively measured (major improvement, minor improvement, status quo or worsening)
  • Assessment of the safety profile [ Time Frame: Throughout the trial (8 weeks) ]
    All clinical and laboratory adverse events will be assessed and recorded.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 29, 2021)
  • Exploratory measurement: Changes in the levels of cytokines and growth factors in the wound fluid [ Time Frame: Wound fluid is collected at three time points: Before initiation of the study drug/placebo (Day 0), after two weeks of treatment (Day 14) and at the end of the treatment period (Day 28). ]
    Changes in the levels of each cytokine and growth factor will be quantified over time
  • Exploratory measurement: Wound status [ Time Frame: Throughout the trial (8 weeks) ]
    Degree of inflammation, granulation tissue, necrosis/slough, exudation and infection. Semi-quantitatively measured.
  • Exploratory measurement: Changes in the microbiome (number of viable bacteria) [ Time Frame: Before initiation of study drug and after two weeks of treatment ]
    Assessed by the colony-forming unit (CFU)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effect of rhGM-CSF on the Healing of Venous Leg Ulcers
Official Title  ICMJE Effect of Topical rhGM-CSF on the Healing of Venous Leg Ulcers: a Randomized, Placebo-controlled, Double-blind, Clinical Phase II Study
Brief Summary The objective of this study is to examine whether local administration of the growth factor rhGM-CSF incorporated into a hydrogel, can accelerate wound healing when applied to venous leg ulcers, and whether this is safe.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
A randomized, placebo-controlled and double-blind, phase II clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Venous Leg Ulcer
Intervention  ICMJE
  • Drug: rhGM-CSF + hydrogel
    The active substance: molgramostim (rhGM-CSF)
    Other Names:
    • Repogel
    • Molgramostim
  • Drug: Placebo hydrogel
    Placebo hydrogel
  • Other: Standard care
    Compression therapy and neutral dressings
Study Arms  ICMJE
  • Experimental: GM-CSF
    rhGM-CSF (molgramostim) + hydrogel
    Interventions:
    • Drug: rhGM-CSF + hydrogel
    • Other: Standard care
  • Placebo Comparator: Placebo
    Hydrogel
    Interventions:
    • Drug: Placebo hydrogel
    • Other: Standard care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 29, 2021)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 30, 2022
Estimated Primary Completion Date May 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men and women aged aged 18 years or older
  2. Patients with at least one difficult-to-heal venous leg ulcer on standard care (diagnosed by clinical evaluation) localized between the knee and ankle, including the perimalleolar area.
  3. Venous insufficiency confirmed by a venous Doppler/duplex ultrasound scan. A previous scan before randomization can be used. If there is no previous adequate scanning, a new scanning has to be performed before randomization.
  4. Ulcer size 2-75 cm2 at randomization day (D0), the upper limit being defined as the largest ulcer in size that fits the area selection criteria
  5. Ulcer duration ≥2 months and ≤3 years
  6. Negative p-HCG for women of childbearing potential
  7. Patient able to understand Danish
  8. Patient able to comply with the protocol
  9. Patient fully informed about the study and having given written informed consent

Exclusion Criteria:

  1. Characteristics of the index ulcer:

    1. Exposed bone, tendon, ligament, cartilage, joint or muscle
    2. Cellulitis or clinical ulcer infection at the screening day D-4, or the day of randomization, D0.
    3. Ulcers adjacent to the index ulcer that could interfere with the index ulcer, as judged by investigator
  2. Patients that are unsuitable for the compression therapy used in the study
  3. Known allergy towards GM-CSF, excipients or any other substances or remedies used in the trial.
  4. Vascularization: Ankle-brachial index ≤0.7
  5. Active or history of following diseases:

    1. Cancer (past history of well-treated cancer is however accepted after a control period of more than two years).
    2. Following autoimmune diseases: rheumatoid arthritis, autoimmune thrombocytopenia, thyroiditis, psoriasis, nephritis or multiple sclerosis.
    3. Lower extremity deep venous thrombosis within the last 3 months
  6. Any of following active diseases:

    1. Serious heart disease, including unstable angina pectoris, a major cardiac event such as myocardial infarction, congestive heart failure NYHA class III-IV within 3 months before the study
    2. Neutrophilic dermatoses (e.g. pyoderma gangrenosum and Sweet's syndrome)
    3. Severe renal-, hepatic or pulmonary insufficiency or severely dysregulated diabetes, as judged by investigator
    4. Myeloproliferative diseases and hematologic diseases (e.g. myelodysplastic syndrome and leukemia). Anemia due to chronic infection or due to deficiency of iron, B12 or folic acid is accepted if Hb >5 mmol/L).
    5. Significant dementia
  7. Biochemistry with clinically significant abnormalities that could preclude study participation as judged by the investigator, such as:

    1. eGFR <20 mL/min/1.73 m2
    2. Hb <5 mmol/L
    3. ALAT >1.5 x upper limit of normal value
    4. Albumin < 20 g/l
  8. Prohibited therapy:

    1. Systemic immunosuppressive treatment, immunomodulators, cytotoxic chemotherapy (exception: usage of corticosteroids) on D-4 or D0.
    2. Corticosteroids with a daily dose equivalent to >10 mg of prednisolone per day on D-4 or D0.
    3. Topical corticosteroids in the index ulcer bed or within 1 cm of the ulcer edge on D-4 or D0.
    4. Biologics within 3 months of D-4 (anti-VEGF treatment in the eye in e.g. diabetics is however allowed).
  9. Weight <50 kg or BMI >50
  10. Participation in another clinical trial
  11. Planned surgery or hospitalization during trial
  12. Pregnant or lactating woman. Positive pregnancy test during run-in.
  13. Failure to agree to using an adequate method of contraception (having a failure rate of < 1% per year) throughout the study period for heterosexually active males and females of childbearing potential, or disagreement to remain abstinent (refrain from heterosexual intercourse). A woman is considered to be of childbearing potential if she is post-menarche and:

    1. Has not reached a postmenopausal state (≥60 years of age and amenorrhea for at least ≥12 months with no identified cause other than menopause, and has not undergone surgical sterilization: removal of ovaries and/or uterus) - OR
    2. No menses for over a year and confirmed by follicle-stimulating hormone (FSH) levels elevated into the postmenopausal range Examples of contraceptive methods with a failure rate of <1% per year includes bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives, hormone-releasing intrauterine devices and copper intrauterine devices. Male participants must be abstinent or use a condom during the trial period.
  14. Blood or sperm donation during trial
  15. Patient has previously been randomized in this study (rescreening is accepted otherwise)
  16. Judgment by the investigator that the patient is not suited for study participation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ewa A Burian, MD +45 53609159 ewa.anna.burian@regionh.dk
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04823962
Other Study ID Numbers  ICMJE Repogel-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ewa Anna Burian, Reponex Pharmaceuticals A/S
Study Sponsor  ICMJE Reponex Pharmaceuticals A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ewa A Burian, MD Department of Dermatology and Copenhagen Wound Healing Center
PRS Account Reponex Pharmaceuticals A/S
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP