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

Venous Leg Ulcer Clinical Trial

Official title:

Effect of Topical rhGM-CSF on the Healing of Venous Leg Ulcers: a Randomized, Placebo-controlled, Double-blind, Clinical Phase II Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04823962
• Other study ID #: Repogel-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 11, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: November 2022
• Source: Reponex Pharmaceuticals A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. completion date: December 30, 2023
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leg Ulcer
• Ulcer
• Varicose Ulcer
• Venous Leg Ulcer

Intervention

Drug:
• rhGM-CSF + hydrogel
The active substance: molgramostim (rhGM-CSF)
• Placebo hydrogel
Placebo hydrogel

Other:
• Standard care
Compression therapy and neutral dressings

Locations

Country	Name	City	State
Denmark	Department of Dermatology and Copenhagen Wound Healing Center, Bispebjerg Hospital	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Reponex Pharmaceuticals A/S

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory measurement: Changes in the levels of cytokines and growth factors in the wound fluid	Changes in the levels of each cytokine and growth factor will be quantified over time	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).
Other	Exploratory measurement: Wound status	Degree of inflammation, granulation tissue, necrosis/slough, exudation and infection. Semi-quantitatively measured.	Throughout the trial (8 weeks)
Other	Exploratory measurement: Changes in the microbiome (number of viable bacteria)	Assessed by the colony-forming unit (CFU)	Before initiation of study drug and after two weeks of treatment
Primary	Proportion of patients reaching a 40% ulcer area reduction, or more, 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)	4 weeks after initiation of the study drug treatment/placebo
Secondary	Absolute change of the ulcer area	The ulcer size is compared in terms of change in cm2 from the randomization day	4 and 8 weeks after randomization
Secondary	Percentage change of the ulcer area	The ulcer size is compared in terms of percentage change from the randomization day	4 and 8 weeks after randomization
Secondary	Complete ulcer healing	Number of subjects reaching complete ulcer healing; Full epithelization and no drainage of wound fluid or dressing requirements	4 and 8 weeks after randomization
Secondary	Time to complete ulcer healing	Time to complete ulcer healing in days, with the randomization day as baseline	Through study completion (8 weeks)
Secondary	Clinical improvement of the wound healing process	Semi-quantitatively measured (major improvement, minor improvement, status quo or worsening)	4 and 8 weeks after randomization
Secondary	Assessment of the safety profile	All clinical and laboratory adverse events will be assessed and recorded.	Throughout the trial (8 weeks)