Phase I/II Dose Ranging CHRONSEAL® Study in Venous Leg Ulcers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if the investigational medicinal product CHRONSEAL intended for future treatment of chronic venous leg ulcers is safe and tolerated and if it has an ulcer size reduction effect when administered to individuals suffering from venous leg ulcers.

Official Title
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A Phase I/II Double-Blind, Dose Ranging, Vehicle Controlled, Randomized, Parallel Groups, Safety, Tolerability and Efficacy Study of CHRONSEAL® (5-amino-acid Deleted Recombinant Human Hepatocyte Growth Factor (KP-dHGF)), in Subjects With Venous Leg Ulcers

Conditions
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Chronic Venous Leg Ulcers

Intervention / Treatment
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* Drug: CHRONSEAL


Participation Criteria
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Eligibility Criteria
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Inclusion criteria (Run-in period): Caucasian male or clinically sterile female subjects 40 years or older. Ankle brachial index of at least 0.6. Written informed consent obtained. Subject legally competent and able to communicate effectively. Subject likely to co-operate. Uncomplicated venous ulcer as by clinical diagnosis. Full skin ulcer. Localisation above the foot and below the knee (wrist and malleoli included) Duration of at least 3 months. Area 3-20 cm2. Exclusion criteria (Run-in period) Visible signs of infection, black necrosis or discharge in the target ulcer. More than  20% slough after debridement. Ulcer that by location or extension will either be difficult to follow or to treat according to the protocol. Other known etiology of the target ulcer. Subject having to the discretion of the investigator clinically significant findings on physical examination or vital signs. Concomitant systemic or topical treatment within 14 days prior to start of study medication with antibiotics or antiseptics for treatment of ulcer infection in target ulcer. Concomitant systemic treatment within 14 days prior to start of study medication with immunosuppressives Concomitant topical treatment within 14 days prior to start of study medication with any of the following: NSAIDs, aspirin Growth factors, or other biologically active agents Products containing chlorhexidine, potassium permanganate, iodine or silver Diabetes Mellitus requiring pharmaceutical treatment. Co-morbidity with a life expectancy less than 6 months. Co-morbidity expected to lower compliance. Diagnosed kidney disease Individuals sensitive to any of the study medication components. Subject having received an investigational drug product, or been enrolled in other investigational drug protocols within a period of 30 days prior to receiving the first dose of the study medication. Known abuse of alcohol, drugs or pharmaceuticals. Diagnosis of squamous epithelia carcinoma Diagnoses of a serious psychiatric illness which may influence study participation. Inclusion criteria (Randomization) Subject likely to co-operate. Ulcer area reduction less than 50% during run-in period. Ulcer area 3-20 cm2. Exclusion criteria (Randomization) 1.& 2. = Run-in period criteria 1. & 2. 3. Subject having to the discretion of the investigator clinically significant findings on vital signs or laboratory values. 4.-10. = Run-in period criteria 6., 7., 8., 11., 12., 13., & 14

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle<br> | Drug: CHRONSEAL<br>* Cream (1.4/2.8 g depending on ulcer size) topical administration, every 2nd day at 3 occasions<br>|
| Experimental: Low dose<br> | Drug: CHRONSEAL<br>* Cream (1.4/2.8 g depending on ulcer size) topical administration, every 2nd day at 3 occasions<br>|
| Experimental: High dose<br> | Drug: CHRONSEAL<br>* Cream (1.4/2.8 g depending on ulcer size) topical administration, every 2nd day at 3 occasions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate safety and local tolerance of CHRONSEAL® cream containing 2 different concentrations of API, applied at 3 occasions every second day in chronic venous leg ulcers compared to vehicle. |  | From start of treatment to 12 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To investigate the treatment effect on ulcer area reduction and changes of ulcer condition of CHRONSEAL® cream, containing 2 different concentrations API, applied at 3 occasions every second day in chronic venous leg ulcers compared to vehicle. |  | From start of treatment to 12 weeks post treatment |