Autologous Skin Substitute for Chronic Leg/Foot Ulcers.

Study Overview
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Brief Summary
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A prospective, multicenter, randomised controlled phase II study in which patients with therapy resistant (arterio-) venous leg/foot ulcers are treated with Tiscover® (test group) or with AS210 (control group) to determine the safety and relative efficacy of both products.

Detailed Description
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Multicenter, randomised clinical trial in out patient in which patients with chronic (arterio-) venous leg/foot ulcers are treated with an autologous cultured human living skin substitute (Tiscover®: test group) or with Acellular donor dermis (AS210: control group). During a pre-inclusion evaluation period of 4 weeks (non healing) chronicity of ulcer is ensured (ulcer size change of < 30%). To determine ulcer type ABI, Doppler and CEAP is performed. The test group will receive 2 applications of Tiscover®. Week 0: wound activating pre-treatment, application of at least one quarter of the wound surface. Week 1: removal of patches, application of patches on total wound surface. The control group (16 patients) will follow the same application protocol.

Official Title
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A Phase II Randomized Multicenter Study on Efficacy and Safety of Cultured Autologous Skin (Tiscover®) and Acellular Dermal Matrix (AS210) in Chronic (Arterio-)Venous Ulcers

Conditions
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Varicose Ulcer

Intervention / Treatment
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* Drug: Tiscover
* Other: AS210


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Have a (arterio) venous leg ulcer (VLU) between the knee and ankle (at or above the malleolus), or on foot (not plantar side of the foot) with a surface area ≥ 1.0 cm2 and ≤ 40.0 cm2 Venous insufficiency confirmed by duplex Doppler ultrasound examination for valvular or venous incompetence. Arterial supply adequacy confirmed (ABPI ≥ 0.6 and ≤ 1.3) Target ulcer involves a full thickness skin loss, but WITHOUT exposure of tendon, muscle, or bone. Ulcer depth < 1 cm Target ulcer duration ≥ 12 weeks but ≤ 15 years Acceptable state of health and nutrition Mobile, at least able to walk with medical walker, and able to return for required treatments and study evaluations Exclusion Criteria: History of anaphylaxis, serum sickness, or erythema multiforme reaction to bovine serum proteins, gentamycin. Therapy with another investigational agent within thirty (30) days of Screening, or during the study. A target ulcer of non-venous etiologies (e.g., sickle cell anemia, necrobiosis lipoidica diabeticorum, pyoderma gangrenosum, vasculopathic or vasculitic). Documented history of osteomyelitis at the target wound location within 6 months preceding the Screening Visit. Refusal of or inability to tolerate compression therapy. Therapy of the target ulcer with autologous skin graft, Apligraf™, or Dermagraft™ within 30 days preceding the Screening Visit. History of cancer in the preceding 5 years (other than carcinoma in situ of the cervix or adequately treated non-melanoma skin cancers). >30% change of wound size in 4 weeks or confirmed by historical data Presence of deep vein thrombosis or contra indication for compression therapy Severe co-morbidity reducing life expectance to < 1 year Use of oral corticosteroids and/or cytostatics >20 mg/per day; Severe infection of ulcer, active cellulitis, osteomyelitis Severe malnutrition Uncontrolled diabetes mellitus, HbA1c > 12% (108 mmol/mol) Anaemia Hb <6 mmol/l

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: autologous cultured skin<br>autologous cultured skin patches (Tiscover) is applied on wound in 2-step procedure with 1 week interval. Dosage: number of patches depends on wound size. Application week 0 is removed after one week (week1). Week 1: wound is completely covered with new Tiscover patches. | Drug: Tiscover<br>* two step procedure, week 0 and week1. Dosage depends on wound size.<br>* Other names: autologous skin substitute;|
| Active Comparator: acellular donor dermis<br>acellular donor dermis (AS210) is applied on wound in 2-step procedure with 1 week interval. Dosage: number of patches depends on wound size. Application week 0 is removed after one week (week1). Week 1: wound is completely covered with new AS210 patches. | Other: AS210<br>* two step procedure, week 0 and week1. Dosage depends on wound size.<br>* Other names: Acellular donor dermis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with complete wound closure after 26 weeks. | The primary objective of this study is to demonstrate the superiority of Tiscover® compared to AS210 for achieving wound healing in subjects with a chronic (arterio) venous leg or foot ulcer. | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time in days to complete wound closure from baseline. |  | 12 weeks | 
| • Proportion of subjects with complete wound closure at each of the 12 treatment weeks. |  | 12 weeks | 
| Percentage of wound closure |  | 12 and 26 weeks | 
| Proportion of subjects with durable wound healing over the 3 months following complete wound closure |  | 3 months and 6 months follow up | 
| Wound size reduction | The percentage of reduction in wound area | 12 and 26 weeks | 
| Pain | Measured with VAS Pain scale | week 0, 1,2,4,8,12, 26 weeks and follow up | 
| Quality of Life | Measured with SF 36 | Week 0, 12, 26 weeks and follow up | 
| Number of SAE |  | 12, 26 weeks and follow up |