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

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

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.

Inclusion criteria (Run-in period):

1. Caucasian male or clinically sterile female subjects
2. 40 years or older.
3. Ankle brachial index of at least 0.6.
4. Written informed consent obtained.
5. Subject legally competent and able to communicate effectively.
6. Subject likely to co-operate.
7. Uncomplicated venous ulcer as by clinical diagnosis.
8. Full skin ulcer.
9. Localisation above the foot and below the knee (wrist and malleoli included)
10. Duration of at least 3 months.
11. Area 3-20 cm2.

Exclusion criteria (Run-in period)

1. Visible signs of infection, black necrosis or discharge in the target ulcer.

2. More than ~20% slough after debridement.

3. Ulcer that by location or extension will either be difficult to follow or to treat according to the protocol.

4. Other known etiology of the target ulcer.

5. Subject having to the discretion of the investigator clinically significant findings on physical examination or vital signs.

6. 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.

7. Concomitant systemic treatment within 14 days prior to start of study medication with immunosuppressives

8. 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

9. Diabetes Mellitus requiring pharmaceutical treatment.

10. Co-morbidity with a life expectancy less than 6 months.

11. Co-morbidity expected to lower compliance.

12. Diagnosed kidney disease

13. Individuals sensitive to any of the study medication components.

14. 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.

15. Known abuse of alcohol, drugs or pharmaceuticals.

16. Diagnosis of squamous epithelia carcinoma

17. Diagnoses of a serious psychiatric illness which may influence study participation.

Inclusion criteria (Randomization)

1. Subject likely to co-operate.
2. Ulcer area reduction less than 50% during run-in period.
3. 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