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

• ClinicalTrials.gov Identifier: NCT00797706
• Recruitment Status: Unknown
• First Posted: November 25, 2008
• Last Update Posted: February 5, 2010
• Sponsor: Kringle Pharma Europe AB
• Collaborator: Kringle Pharma, Inc.
• Information provided by: Kringle Pharma Europe AB

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Venous Leg Ulcers	Drug: CHRONSEAL	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: November 2008
• Estimated Primary Completion Date: March 2010
• Estimated Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Vehicle	Drug: CHRONSEAL; Cream (1.4/2.8 g depending on ulcer size) topical administration, every 2nd day at 3 occasions
Experimental: Low dose	Drug: CHRONSEAL; Cream (1.4/2.8 g depending on ulcer size) topical administration, every 2nd day at 3 occasions
Experimental: High dose	Drug: CHRONSEAL; Cream (1.4/2.8 g depending on ulcer size) topical administration, every 2nd day at 3 occasions

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: From start of treatment to 12 weeks post treatment ]

Secondary Outcome Measures :

1. 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. [ Time Frame: From start of treatment to 12 weeks post treatment ]

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Norway

Medi3 Innlandet AS, Department Elverum

Elverum, Norway, 2402

Hudavdelingen Helse

Førde, Norway, 6807

Medi 3 Innlandet AS, Department Hamar

Hamar, Norway, 2317

Colosseumklinikken

Oslo, Norway, 0369

Sweden

Vårdcentralen Alvesta

Alvesta, Sweden, 342 30

Danderyds Sjukhus AB

Danderyd, Sweden, SE-182 88

Carema Vårdcentral Gubbängen

Enskede, Sweden, SE-122 45

Department of Dermatology and Infectious diseases

Halmstad, Sweden, SE-301 85

Husläkarna i Kungsbacka

Kungsbacka, Sweden, SE-434 30

Department of Dermatology, Lund University hospital

Lund, Sweden, SE-221 85

Department of Dermatology, University Hospital MAS

Malmö, Sweden, SE-205 02

Gamla Stans Vårdcentral

Stockholm, Sweden, SE-111 29

Taptogatans Husläkare

Stockholm, Sweden, SE-115 26

Department of Dermatology, Norrlands University hospital

Umeå, Sweden, SE-901 85

Department of Medical Sciences, Section of Dermatology and Venereology, Uppsala University hospital

Uppsala, Sweden, SE-751 05

Neptunuskliniken

Varberg, Sweden, SE-432 44

Sponsors and Collaborators

Kringle Pharma Europe AB

Kringle Pharma, Inc.

Investigators

• Principal Investigator: Hans Olav Høivik, MD; Medi 3 Innlandet AS, avd Hamar
• Principal Investigator: Karin Andersson, MD; Halland County Council, Department of Dermatology and Infectious diseases, Halmstad, Sweden
• Study Chair: Jan Apelqvist, Assoc. Prof., PhD, MD; Department of Endocrinology, University Hospital Malmö,

More Information

• Responsible Party: Prof. Anders Vahlne/CEO, Kringle Pharma Europe AB
• ClinicalTrials.gov Identifier: NCT00797706
• Other Study ID Numbers: CS-201; EudraCT No. 2007-002695-34
• First Posted: November 25, 2008
• Last Update Posted: February 5, 2010
• Last Verified: February 2010

Additional relevant MeSH terms:

Varicose Ulcer; Leg Ulcer; Ulcer; Pathologic Processes; Skin Ulcer; Skin Diseases; Varicose Veins; Vascular Diseases; Cardiovascular Diseases