Venous leg ulcers MedDRA version: 21.1 Level: LLT Classification code 10047260 Term: Venous ulceration System Organ Class: 100000004858
Conditions
Interventions
Product Name: Repogel
Pharmaceutical Form: Gel
INN or Proposed INN: MOLGRAMOSTIM
CAS Number: 99283-10-0
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number
Sponsors
Reponex Pharmaceuticals A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women aged =18 years 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: 1. Characteristics of the index ulcer: a. Exposed bone, tendon, ligament, cartilage, joint or muscle b. Cellulitis or clinical ulcer infection at the screening day D-4, or the day of randomization, D0. c. 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: a. Cancer (past history of well-treated cancer is however accepted after a control period of more than two years). b. Following autoimmune diseases: rheumatoid arthritis, autoimmune thrombocytopenia, thyroiditis, psoriasis, nephritis or multiple sclerosis. c. Lower extremity deep venous thrombosis within the last 3 months 6. Any of following active diseases: a. 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 b. Neutrophilic dermatoses (e.g. pyoderma gangrenosum and Sweet’s syndrome) c. Severe renal-, hepatic or pulmonary insufficiency or severely dysregulated diabetes, as judged by investigator d. 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). e. Significant dementia 7. Biochemistry with clinically significant abnormalities that could preclude study participation as judged by the investigator, such as: a. eGFR 1.5 x upper limit of normal value d. Albumin 10 mg of prednisolone per day on D-4 or D0. c. Topical corticosteroids in the index ulcer bed or within 1 cm of the ulcer edge on D-4 or D0. d. Biologics within 3 months of D-4 (anti-VEGF treatment in the eye in e.g. diabetics is however allowed). 9. Weight 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: a. 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 b. 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. Bloo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 will be evaluated by measuring the ulcer area change after 4 weeks of treatment compared to placebo. ;Secondary Objective: To study the effect of topical rhGM-CSF on complete wound healing, the time to complete healing and a clinical evaluation of the wound healing process. The safety and the mechanisms of action of the intervention will be studied as well. Finally, the effect of topical rhGM-CSF on inflammation will be studied in terms of clinical signs and relevant biomarkers in the wound microenvironment, as well as studies on the microbiome.;Primary end point(s): Proportion of patients reaching a 40% ulcer area reduction, or more, 4 weeks after initiation of the study drug treatment/placebo;Timepoint(s) of evaluation of this end point: 4 weeks after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Absolute and percentage change of the ulcer area 2. Complete ulcer healing 3. Time to complete ulcer healing 4. Clinical improvement of the wound healing process 5. Degree of inflammation, granulation tissue, necrosis/slough, exudation and infection 6. Changes in the levels of cytokines and growth factors in the wound fluid 7. Changes in the microbiome 8. Assessment of the safety profile;Timepoint(s) of evaluation of this end point: Please see protocol. | — |
Countries
Denmark
Contacts
Public ContactClinical Trials Information
Department of Dermatology and Copenhagen Wound Healing Center
Outcome results
None listed