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.

Study Overview

• Status: Terminated
• Conditions: Varicose Ulcer
• Intervention / Treatment: Drug: Tiscover; Other: AS210

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands, 1817 MS
    • Centrum Oosterwal
  • Almere, Netherlands
    • Flevo Ziekenhuis, afdeling dermatologie
  • Amsterdam, Netherlands, 1081HZ
    • VU University Medical Center
  • Rotterdam, Netherlands
    • St. Fransiscus Gasthuis
  • Zwolle, Netherlands
    • Isala Ziekenhuis, dermatologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: autologous cultured skin; 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; two step procedure, week 0 and week1. Dosage depends on wound size.; Other Names: autologous skin substitute
Active Comparator: acellular donor dermis; 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; two step procedure, week 0 and week1. Dosage depends on wound size.; Other Names: Acellular donor dermis

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chantal Blok
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Study Chair: Susan Gibss, Prof.dr., VU medical center, department of dermatology

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 29, 2015
• First Submitted That Met QC Criteria: February 4, 2015
• First Posted (Estimate): February 10, 2015

Study Record Updates

• Last Update Posted (Estimate): January 7, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Leg Ulcer; Skin Ulcer; Varicose Veins; Ulcer; Varicose Ulcer
• Other Study ID Numbers: TIS2012