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 skin defects in adults and children in comparison to autologous split-thickness skin grafts (STSG)

Large full thickness skin defects requiring definitive coverage are frequently
encountered in various contexts in both children and adults. They typically
result from injuries (e.g. burns, injuries), illness (e.g. septic skin
necrosis), or when extended (re)constructive surgical procedures are to be
performed. The coverage of such extended lesions still poses a very significant
challenge: the functionally and cosmetically best therapeutic option would be
transplanting full thickness autologous skin, as this basically leads to
reconstitution of a normal skin in terms of both function and cosmetics.
However, donor sites are limited in a prohibitive way when there is extensive
demand (>2-3% total body surface area (TBSA)). By using a dermal template (e.g.
Integra Regenerative Template) in combination with a STSG the functional and
aesthetic outcome can be improved, but will never reach the outcome of full
thickness skin grafts. Furthermore, the two stage procedure is highly time
consuming (e.g. 5/6 weeks in reconstructive procedures), since the formation of
a neodermis has to be awaited before the STSG can be done.
In view of all above considerations, in particular based on the fact that only
full thickness skin transplants yield truly excellent long-term results when
the entire skin has to be replaced, the vision to build autologous skin
analogues in the laboratory by means of tissue engineering has been developed.

The proposed phase II clinical trial aims to evaluate the safety and efficacy
of EHSG-KF, a bioengineered autologous dermo-epidermal skin substitute, in
adults and children with large skale full thickness skin defects, when compared
to split-thickness skin grafts (STSG), the current gold standard.

This study has been transitioned to CTIS with ID 2024-512190-27-00 check the CTIS register for the current data.

To evaluate the efficacy and safety of EHSG-KF in comparison to STSG (unmeshed
or meshed up to 1:3) in adults and children with large full thickness skin
defects.

Primary Objective:
To evaluate the efficacy of EHSG-KF in comparison to STSG based on the
assessment of:
- Scar quality:
o POSAS questionnaire, observer total score 3 months post grafting

Secondary Objectives
To evaluate the safety and efficacy of EHSG-KF in comparison to STSG (unmeshed
or meshed up to 1:3) based on the assessment of:
- Scar quality:
o Cutometer® 3 months post grafting
o POSAS questionnaire, observer items 3 months post grafting
o POSAS questionnaire, patient items and total score 3 months post grafting
o DSM ColorMeter® (1 year post grafting)
o Biopsies of the study area and control area (1 year post grafting) for
histological assessment. (optional)
- Infection 6-10 days and 3 weeks post grafting
- Graft take at 6-10 days post grafting
- % Epithelialization at 4 weeks post grafting
- Adverse events
- QOL assessment at (1 year) post grafting
o EQ-5D and BSHS-B for patients >=18 years with reconstruction of burn scars,
o EQ-5D only for patients >=18 years without burn scars,
o EQ-5DY and PedsQL for patients <18 years
- Ratio of covered surface area to biopsy site/donor site surface area 4 weeks
post grafting

Open label, intra-patient randomised, prospective, multi-centre phase II
clinical trial.
Intra-patient randomisation means that each patient has 2 spots, A and B, each
with a size of 45-90cm2 that are selected. Each spot is covered with either the
standard method (meshed STSG) or EHSG-KF, and it is determined in advance which
treatment will be applied to which spot. The endpoints are measured and
compared.

Product; EHSG-KF is an autologous tissue-engineered dermo-epidermal skin
substitute on a collagen type I hydrogel. The size per graft is 45+/-4cm2 and
the thickness is 0.5-2 mm.

Intervention: Grafting of the wound bed (=experimental area) with 1 to 2 grafts
of EHSG-KF.

The experimental product potentially offers a better therapeutic option than
STSG alone. EHSG-KF has been successfully tested in the phase I clinical trial
and several preclinical studies without significant adverse reactions and, as
the skin grafts are autologous, no unusually high incidence of
complications/adverse effects is anticipated. If the working hypothesis proves
true, then graft take and wound healing dynamics will be similar to those of
STSG, while the efficacy, in terms of scar quality and final functional and
cosmetic results, will be even better than obtained from STSG alone. Currently
the product is under investigation and ongoing risk will be assessed and risk
mitigation strategies are included in the study protocol. Based on the
available study results, we do not believe the risk associated with this
product is greater than the usual treatment.