Autologous Skin Substitute for Chronic Leg/Foot Ulcers.

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

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.

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.

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