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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Skin Wound

Intervention / Treatment
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* Biological: EHSG-KF
* Biological: STSG


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Year

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scar, Skin, Wound Healing, Tissue Engineering, Dermis, Epidermis