Study With an Autologous Dermo-epidermal Skin Substitute for the Treatment of Burns in Adults and Adolescents

Study Overview
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Brief Summary
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This phase IIb trial aims to evaluate the efficacy and safety of EHSG-KF (synonym denovoSkin) in comparison to meshed STSG in adults and adolescents with partial deep dermal and full thickness burns.

Detailed Description
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This multicentre phase IIb clinical trial will target adults and adolescents with severe burns to elucidate the benefit of a tissue-engineered autologous skin substitute for the patient group with the highest mortality rates. Particular emphasis, apart from safety, will be placed on efficacy, including the ratio of covered surface area to harvested surface area and scar quality, in comparison to meshed STSG.

Official Title
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A Phase IIb, 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 Partial Deep Dermal and Full Thickness Burns in Adults and Adolescents in Comparison to Autologous Split-thickness Skin Grafts (STSG)

Conditions
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Burns

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: ≥12 years of age Deep partial thickness and/or full thickness burns requiring surgical wound coverage Expected that ≥90 cm2 of wound (not counting the head and neck area for study patients in The Netherlands) will remain open at 4 weeks post burn despite proceeding with treatment in accordance with the standard of care. >20% TBSA burns can be taken as guideline, but TBSA is not an inclusion criterion. 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) Wounds in the head and neck area as study target area (only applicable for study patients in The Netherlands) Enrolment of the Investigator, his/her family members, employees and other dependent persons

Ages Eligible for Study
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Minimum Age: 12 Years

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 meshed STSG based on ratio of covered surface | Efficacy of EHSG-KF in comparison to meshed STSG based on ratio of covered surface area to biopsy site/donor site surface area | 4 weeks post grafting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of EHSG-KF in comparison to meshed STSG based on clinical signs of infection | Evaluation of clinical signs of infection at experimental area and control area | 4-11 days post grafting and 21 +/-2 days post grafting | 
| Safety of EHSG-KF in comparison to meshed STSG based on microbiological signs of infection | Evaluation of microbiologic signs of infection at experimental area and control area | 4-11 days post grafting and 21 +/-2 days post grafting | 
| Efficacy of EHSG-KF in comparison to meshed STSG based on evaluation of scar quality by measurement of the elasticity using Cutometer(R) | Assessment of elasticity of experimental area and control area using Cutometer(R) | 1 year +/-30 days post grafting | 
| Efficacy of EHSG-KF in comparison to meshed STSG based on evaluation of scar quality by assessment of General scar quality using POSAS assessment tool | Assessment of general scar Quality of experimental area and control area using POSAS assessment tool | 1 year +/-30 days post grafting | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Burns, Scar, Skin, Wound healing, Tissue Engineering, Dermis, Epidermis, Thermal Injuries