Autologous Skin Substitute for Chronic Leg/Foot Ulcers.

Varicose Ulcer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02360358
• Other study ID #: TIS2012
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: January 29, 2015
• Last updated: January 6, 2016
• Start date: August 2012
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Dutch Health Care Inspectorate
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ulcer
• Varicose Ulcer

Intervention

Drug:
• Tiscover
two step procedure, week 0 and week1. Dosage depends on wound size.

Other:
• AS210
two step procedure, week 0 and week1. Dosage depends on wound size.

Locations

Country	Name	City	State
Netherlands	Centrum Oosterwal	Alkmaar
Netherlands	Flevo Ziekenhuis, afdeling dermatologie	Almere
Netherlands	VU University Medical center	Amsterdam
Netherlands	St. Fransiscus Gasthuis	Rotterdam
Netherlands	Isala Ziekenhuis, dermatologie	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
Chantal Blok	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Time in days to complete wound closure from baseline.		12 weeks	No
Secondary	• Proportion of subjects with complete wound closure at each of the 12 treatment weeks.		12 weeks	No
Secondary	Percentage of wound closure		12 and 26 weeks	No
Secondary	Proportion of subjects with durable wound healing over the 3 months following complete wound closure		3 months and 6 months follow up	No
Secondary	Wound size reduction	The percentage of reduction in wound area	12 and 26 weeks	No
Secondary	Pain	Measured with VAS Pain scale	week 0, 1,2,4,8,12, 26 weeks and follow up	No
Secondary	Quality of Life	Measured with SF 36	Week 0, 12, 26 weeks and follow up	No
Secondary	Number of SAE		12, 26 weeks and follow up	Yes