Evaluation of EHSG-KF, a Bilayer Engineered Collagen Hydrogel-Based Skin Graft, Versus Autologous Split-Thickness Skin Grafts in Full-Thickness Skin Defects

The primary objective of this study is to evaluate the **efficacy** and safety of the autologous bio-engineered dermo-epidermal skin substitute, EHSG-KF, in comparison to autologous split-thickness skin grafts (STSG) in adults and children with large full-thickness skin defects. The primary focus is on assessing scar quality using the POSAS questionnaire, specifically the observer total score, three months post-grafting. This evaluation is clinically relevant as it aims to determine the potential of EHSG-KF to improve scar outcomes, which is a critical factor in the recovery and quality of life for patients with significant skin defects.

Secondary objectives include evaluating the safety and efficacy of EHSG-KF compared to STSG based on several parameters: - Scar quality assessed by Cutometer® and POSAS questionnaire (observer and patient items) three months post-grafting, and DSM ColorMeter® one year post-grafting. Optional biopsies for histological assessment may be conducted one year post-grafting. - Infection rates at 6-10 days and 3 weeks post-grafting. - Graft take at 6-10 days post-grafting. - Percentage of epithelialization at 4 weeks post-grafting. - Adverse events monitoring. - Quality of life (QOL) assessment one year post-grafting using EQ-5D and BSHS-B for patients aged 18 and older with burn scar reconstruction, EQ-5D for those without burn scars, and EQ-5DY and PedsQL for patients under 18. - Ratio of covered surface area to biopsy site/donor site surface area 4 weeks post-grafting.

The clinical trial involves a total of **5 participants** comprising both **male and female** subjects. The study population includes **adults and children** with **full-thickness skin defects**. Participants are selected based on specific criteria, including an age requirement of **1 year and older**. The trial targets individuals with large full-thickness defects necessitating coverage post-excision of various conditions such as scars, benign skin tumors, and soft tissue defects following trauma or infection. The trial population includes a vulnerable group, indicating special considerations for ethical and safety measures. Participants' general health status is not specified, and no specific lifestyle considerations such as diet or physical activity are mentioned. The sponsor has not provided additional information regarding the selection process or other demographic details.

The clinical trial is a **Phase II**, prospective, intra-patient randomized controlled, multicenter study designed 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. The trial compares EHSG-KF to autologous split-thickness skin grafts (STSG). The study is expected to run from February 2018 to August 2026, with participant involvement lasting up to one year post-grafting. The trial includes several key elements of research methodology, such as randomization and control, to ensure the reliability and validity of the results.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥1 year) and the presence of large full-thickness skin defects. Following the screening, participants will attend multiple follow-up visits to assess the primary and secondary endpoints. The primary endpoint involves evaluating the efficacy of EHSG-KF compared to STSG based on scar quality using the POSAS questionnaire at visit 8, which occurs 90 days post-grafting. Secondary endpoints include additional assessments of scar quality, clinical and microbiologic signs of infection, and quality of life evaluations at various intervals, including visits 4, 5, 6, and 10, with the latter occurring one year post-grafting.

The expected length of participant involvement is approximately one year, with conditions for early termination including withdrawal of consent or adverse events that compromise participant safety. The study is conducted under strict ethical guidelines, ensuring informed consent is obtained from all participants or their legally authorized representatives. The trial's design and procedures are structured to provide comprehensive data on the safety and efficacy of the EHSG-KF product, contributing valuable insights into its potential as a treatment for full-thickness skin defects.

The clinical trial involves the use of an **experimental medication** known as EHSG-KF, which is a **bilayer engineered collagen hydrogel-based skin graft** composed of autologous keratinocytes and fibroblasts. This product is developed by CUTISS AG and is classified as a **hydrogel** for **cutaneous use**. The EHSG-KF is designed for the treatment of full-thickness skin defects in both adults and children. The maximum daily dose and total dose amount are both limited to 2 units, with a maximum treatment period of 1 day. The product is not a pediatric formulation and is designated as an orphan drug under the number EU/3/15/1596. The EHSG-KF is a living tissue, incorporating autologous, ex-vivo human fibroblasts and keratinocytes, and is categorized as a structurally diverse substance used in cell therapy.

In this study, the **comparator treatment** is the autologous split-thickness skin graft (STSG), which may be used in either an unmeshed form or meshed up to a ratio of 1:3. The STSG serves as the standard-of-care therapy against which the efficacy and safety of EHSG-KF are evaluated. The primary objective of the trial is to assess the efficacy of EHSG-KF in comparison to STSG, with a focus on scar quality as measured by the POSAS questionnaire, specifically the observer total score, three months post-grafting.

Efficacy in this clinical trial will be assessed by comparing the **scar quality** between the treatment sites using the EHSG-KF and control sites using autologous split-thickness skin grafts (STSG). The primary endpoint for efficacy evaluation is the general scar quality, which will be measured using the POSAS (Patient and Observer Scar Assessment Scale) questionnaire. The observer total score will be collected at visit 8, which occurs 90 days ± 5 days post-grafting.

Secondary efficacy endpoints include additional assessments of scar quality. These will involve the use of the Cutometer® to measure parameters such as pliability, extension, elasticity, retraction, and viscoelasticity at visit 8. The POSAS questionnaire will also be used to evaluate both observer and patient items, including vascularity, pigmentation, thickness, relief, pliability, pain, itching, and color at the same timepoint. Further assessments will be conducted using the DSM ColorMeter® to evaluate erythema and pigmentation at visit 10, which is scheduled for 1 year ± 30 days post-grafting. Optional biopsies for histological assessment may be performed at this visit. Additional measures include graft take at visit 4 (6-10 days post-grafting) and percentage epithelialization at visit 6 (28 days ± 3 days post-grafting).

Quality of life (QOL) assessments will also be conducted as part of the secondary efficacy endpoints. These assessments will be performed at visit 10 using the EQ-5D and BSHS-B for patients aged 18 years and older with reconstruction of burn scars, EQ-5D for those without burn scars, and EQ-5DY and PedsQL for patients under 18 years of age.