Effect of rhGM-CSF on the Healing of Venous Leg Ulcers
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GM-CSF rhGM-CSF (molgramostim) + hydrogel |
Drug: rhGM-CSF + hydrogel
The active substance: molgramostim (rhGM-CSF)
Other Names:
Other: Standard care
Compression therapy and neutral dressings
|
| Placebo Comparator: Placebo Hydrogel |
Drug: Placebo hydrogel
Placebo hydrogel
Other: Standard care
Compression therapy and neutral dressings
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients reaching a 40% ulcer area reduction, or more, 4 weeks after initiation of the study drug treatment/placebo [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)
Secondary Outcome Measures
- Absolute change of the ulcer area [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 [4 and 8 weeks after randomization]
The ulcer size is compared in terms of percentage change from the randomization day
- Complete ulcer healing [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 [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 [4 and 8 weeks after randomization]
Semi-quantitatively measured (major improvement, minor improvement, status quo or worsening)
- Assessment of the safety profile [Throughout the trial (8 weeks)]
All clinical and laboratory adverse events will be assessed and recorded.
Other Outcome Measures
- Exploratory measurement: Changes in the levels of cytokines and growth factors in the wound fluid [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 [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) [Before initiation of study drug and after two weeks of treatment]
Assessed by the colony-forming unit (CFU)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Men and women aged aged 18 years or older
-
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.
-
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.
-
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
-
Ulcer duration ≥2 months and ≤3 years
-
Negative p-HCG for women of childbearing potential
-
Patient able to understand Danish
-
Patient able to comply with the protocol
-
Patient fully informed about the study and having given written informed consent
Exclusion Criteria:
-
Characteristics of the index ulcer:
-
Exposed bone, tendon, ligament, cartilage, joint or muscle
-
Cellulitis or clinical ulcer infection at the screening day D-4, or the day of randomization, D0.
-
Ulcers adjacent to the index ulcer that could interfere with the index ulcer, as judged by investigator
-
Patients that are unsuitable for the compression therapy used in the study
-
Known allergy towards GM-CSF, excipients or any other substances or remedies used in the trial.
-
Vascularization: Ankle-brachial index ≤0.7
-
Active or history of following diseases:
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Cancer (past history of well-treated cancer is however accepted after a control period of more than two years).
-
Following autoimmune diseases: rheumatoid arthritis, autoimmune thrombocytopenia, thyroiditis, psoriasis, nephritis or multiple sclerosis.
-
Lower extremity deep venous thrombosis within the last 3 months
-
Any of following active diseases:
-
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
-
Neutrophilic dermatoses (e.g. pyoderma gangrenosum and Sweet's syndrome)
-
Severe renal-, hepatic or pulmonary insufficiency or severely dysregulated diabetes, as judged by investigator
-
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).
-
Significant dementia
-
Biochemistry with clinically significant abnormalities that could preclude study participation as judged by the investigator, such as:
-
eGFR <20 mL/min/1.73 m2
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Hb <5 mmol/L
-
ALAT >1.5 x upper limit of normal value
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Albumin < 20 g/l
-
Prohibited therapy:
-
Systemic immunosuppressive treatment, immunomodulators, cytotoxic chemotherapy (exception: usage of corticosteroids) on D-4 or D0.
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Corticosteroids with a daily dose equivalent to >10 mg of prednisolone per day on D-4 or D0.
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Topical corticosteroids in the index ulcer bed or within 1 cm of the ulcer edge on D-4 or D0.
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Biologics within 3 months of D-4 (anti-VEGF treatment in the eye in e.g. diabetics is however allowed).
-
Weight <50 kg or BMI >50
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Participation in another clinical trial
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Planned surgery or hospitalization during trial
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Pregnant or lactating woman. Positive pregnancy test during run-in.
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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:
-
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
-
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.
-
Blood or sperm donation during trial
-
Patient has previously been randomized in this study (rescreening is accepted otherwise)
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Judgment by the investigator that the patient is not suited for study participation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital | Copenhagen | Denmark |
Sponsors and Collaborators
- Reponex Pharmaceuticals A/S
Investigators
- Principal Investigator: Ewa A Burian, MD, Department of Dermatology and Copenhagen Wound Healing Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Repogel-01