Study With an Autologous Dermo-epidermal Skin Substitute for the Treatment of Full-Thickness Skin Defects in Adults and Children

A Phase II, Prospective, Intra-patient Randomised Controlled, Multicentre Study to Evaluate the Safety and Efficacy of an Autologous Bio-engineered Dermo-epidermal Skin Substitute (EHSG-KF) for the Treatment of Full-Thickness Defects in Adults and Children in Comparison to Autologous Split-thickness Skin Grafts (STSG)

This phase II trial aims to evaluate the efficacy and safety of EHSG-KF (synonym denovoSkin) in comparison to meshed STSG in adults and children with full-thickness Skin defects.

Study Overview

• Status: Active, not recruiting
• Conditions: Skin Wound
• Intervention / Treatment: Biological: EHSG-KF; Biological: STSG

Detailed Description

This multicentre phase II clinical trial will target adults and children with fullt-thickness skin defects to elucidate the benefit of a tissue-engineered autologous skin substitute. Particular emphasis, apart from safety, will be placed on efficacy, e.g. scar quality, in comparison to meshed STSG.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy
    • Unità di Chirurgia Plastica e Ustioni Ospedale Santobono
  • Napoli, Italy
    • Chirurgia Plastica e Centro Ustioni Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli
  • Padova, Italy
    • U.O.C. Grandi Ustionati Azienda Ospedale Università Padova
  • Torino, Italy, 10126
    • Città della Salute
  • Verona, Italy
    • U.O. Chirurgia Plastica e Centro Ustioni Azienda Ospedaliera Universitaria Integrata Verona
• Netherlands
  • Amsterdam, Netherlands, 1081
    • Dept. of Plastic, Reconstructive and Hand Surgery, VU University Medical Center
  • Beverwijk, Netherlands, 1940
    • Rode Kruis Ziekenhuis
• Switzerland
  • Zurich, Switzerland, 8091
    • University Hospital Zurich
  • Zurich, Switzerland, 8032
    • University Children's Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: ≥1 years of age
• Large full-thickness defects that require coverage after excision of: Scars, Benign skin tumors (e.g. neurofibroma), Melanocytic nevus (e.g. giant nevus), Gender reassignment surgery, Soft tissue defect after trauma, Soft tissue defect after infection and debridement (e.g necrotizingn fascitis, hidadentitis suppurativa, purpura fulminans), Flap donorsite (e.g. radial forearm flap)
• Minimal areas requiring coverage (not counting the head and neck area for study patients in The Netherlands): 1-5 years: minimum 9cm2, 6-16 years: minimum 25cm2, >16 years: minimum 45cm2
• Signed Informed consent

Exclusion Criteria:

• Patients tested positive for HBV, HCV, syphilis or HIV
• Patients with known underlying or concomitant medical conditions that may interfere with normal wound healing (e.g. systemic skin and connective tissue diseases, any kind of congenital defect of metabolism including insulin-dependent diabetes mellitus, Cushing syndrome or disease, scurvy, chronic hypothyroidism, congenital or acquired immunosuppressive condition, chronic renal failure, or chronic hepatic dysfunction (Child-Pugh class B or C), severe malnutrition, or other concomitant illness which, in the opinion of the Investigator, has the potential to significantly delay wound healing)
• Severe drug and alcohol abuse
• Pre-existing coagulation disorders as defined by INR outside its normal value, PTT >ULN and fibrinogen <LLN prior to the current hospital admission and / or at the Investigator's discretion
• Patients with known allergies to amphotericin B, gentamicin, penicillin, streptomycin, or bovine collagen
• Previous enrolment of the patient into the current phase II study
• Participation of the patient in another study with conflicting endpoints within 30 days preceding and during the present study
• Patients expected not to comply with the study protocol (including patients with severe cognitive dysfunction/impairment and severe psychiatric disorders)
• Pregnant or breast feeding females
• Intention to become pregnant during the clinical course of the study (12 months)
• Enrolment of the Investigator, his/her family members, employees and other dependent persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EHSG-KF and STSG Transplantation; Transplantation of EHSG-KF to the experimental area and transplantation of STSG (split-thickness skin graft) to the control area	Biological: EHSG-KF; Transplantation of autologous dermo-epidermal skin substitute EHSG-KF to the experimental area; Other Names: denovoSkin; Biological: STSG; Transplantation of autologous split-thickness skin graft to the control area; Other Names: Split-thickness skin graft

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of EHSG-KF in comparison to STSG based on the assessment of scar quality	Efficacy of EHSG-KF in comparison to STSG based on the assessment of scar quality, using the POSAS ("Patient and Observer Scar Assessment Scale"). The reported Observer Total Score can range from 1 (best) to 10 (worst).	3 months post grafting

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of EHSG-KF in comparison to STSG based on the assessment of scar quality	Evaluation of scar quality at experimental area and control area, using Cutometer for elasticity measurement	3 months and 1 year +/- 30 days post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of scar quality	Evaluation of scar quality at experimental area and control area, using POSAS ("Patient and Observer Scar Assessment Scale") Observer Total Score	3 months and 1 year +/- 30 days post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of scar quality	Evaluation of scar quality at experimental area and control area, using POSAS ("Patient and Observer Scar Assessment Scale") Patient Items and Total Score	3 months and 1 year +/- 30 days post grafting
A Efficacy of EHSG-KF in comparison to STSG based on the assessment of scar quality	Evaluation of scar quality at experimental area and control area, using Colormeter for skin colour measurement,.	3 months and 1 year +/- 30 days post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of epithelialisation	Evaluation of efficacy at experimental area and control area, calculating the epithelialized area as percentage of the total grafted area.	28 +/- 3 days post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of graft take.	Evaluation of efficacy at experimental area and control area, assessed by the analysis of the graft take	4-11 days post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of quality of life.	Evaluation of efficacy of experimental and control treatment, assessed by quality of life questionnaires ("Pediatric quality of life inventory")	1 +/- 30 days year post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of quality of life.	Evaluation of efficacy of experimental and control treatment, assessed by quality of life questionnaires ("Patient Observer Scar Assessment Scale")	1 +/- 30 days year post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of quality of life.	Evaluation of efficacy of experimental and control treatment, assessed by quality of life questionnaires ("EuroQuol 5 dimensions questionnaire")	1 +/- 30 days year post grafting
Efficacy of EHSG-KF in comparison to STSG based on the assessment of quality of life.	Evaluation of efficacy of experimental and control treatment, assessed by quality of life questionnaires ("Burn Specific Health Scale Brief")	1 +/- 30 days year post grafting
Safety of EHSG-KF in comparison to STSG based on the assessment of infection rate.	Evaluation of safety at experimental area and control area based on the infection rate, assessed by using wound swabs and clinical evaluation.	4-11 days and 19-23 days post grafting
Safety of EHSG-KF in comparison to STSG based on the assessment of adverse events.	Evaluation of safety at experimental area and control area, assessed by the type and number of adverse events.	through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: CUTISS AG
• Collaborators: University of Zurich; University Hospital, Zürich; Julius Clinical; Sintesi Research Srl; Wyss Zurich
• Investigators: Study Chair: Clemens Sc, Prof., University Children's Hospital, Zurich

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2018
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 9, 2018

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 20, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Epidermis; Skin; Wound Healing; Scar; Dermis; Tissue Engineering
• Other Study ID Numbers: TBRU-dS-RAC-PII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No