Evaluation of the Efficacy and Safety of EHSG-KF, a Bilayer Engineered Collagen Hydrogel-Based Skin Graft, in Adults and Adolescents with Deep Dermal and Full-Thickness Burns

The primary objective of this study is to evaluate the **efficacy** of EHSG-KF, an autologous bio-engineered dermo-epidermal skin substitute, in comparison to meshed split-thickness skin grafts (STSG) in adults and adolescents with partial deep dermal and full-thickness burns. This will be assessed by measuring the ratio of covered surface area to biopsy site/donor site surface area four weeks post-grafting. This evaluation is clinically relevant as it aims to determine the potential of EHSG-KF to provide effective coverage and healing in burn patients, which could lead to improved outcomes and reduced donor site morbidity.

Secondary objectives include:

• Assessing the percentage of epithelialization at three months post-grafting.
• Evaluating the safety and efficacy of EHSG-KF compared to meshed STSG based on infection rates, scar quality (using Cutometer®, DSM ColorMeter®, and POSAS-questionnaire at various intervals post-grafting), graft take at 6-10 days, and time to complete epithelialization at multiple time points post-grafting.
• Monitoring the incidence of wound closure at 4, 8, and 12 weeks post-grafting, growth in surface area between 1 and 3 years post-grafting, and reporting all observed adverse events.
• Conducting quality of life assessments using EQ-5D and BSHS-B for patients aged 18 and older, and EQ-5DY and PedsQL for patients under 18.
• Evaluating healthcare resource utilization, including direct and indirect healthcare costs.

The clinical trial involves a total of **6 participants** who are **adults and adolescents** with **partial deep dermal and full-thickness burns**. The study population includes both **male and female** subjects, aged **12 years and older**. Participants were selected based on specific criteria, including the presence of deep partial thickness and/or full-thickness burns that require surgical wound coverage. The trial population is characterized by individuals who are expected to have at least 90 cm² of wound area remaining open at 4 weeks post-burn, despite receiving standard care treatment. The study includes a vulnerable population, and informed consent was obtained from the patients or their legally authorized representatives. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase IIb**, 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 partial deep dermal and full-thickness burns in adults and adolescents. The trial compares EHSG-KF to autologous split-thickness skin grafts (STSG). The study is expected to conclude by December 31, 2025, with recruitment having commenced on October 1, 2017.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥12 years), the presence of deep partial thickness and/or full-thickness burns requiring surgical wound coverage, and the expectation that ≥90 cm² of the wound will remain open at four weeks post-burn. Informed consent is required from the patient or their legally authorized representative. The primary endpoint is the efficacy evaluation based on the ratio of covered surface area to biopsy site/donor site surface area at visit 6, which occurs 28 ± 3 days post-grafting.

Secondary endpoints include the percentage of epithelialization at visit 8 (90 ± 5 days post-grafting), safety evaluations for clinical and microbiologic signs of infection at visits 4 (6-10 days post-grafting) and 5 (21 ± 2 days post-grafting), and assessments of scar quality and elasticity at visit 10 (1 year ± 30 days post-grafting). Adverse events will be monitored and reported from visit 2 onwards. 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 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 partial deep dermal and full-thickness burns in adults and adolescents. The **pharmaceutical form** of the product is a hydrogel, and it is administered via cutaneous application. The maximum daily dose and total dose amount are both set at 2 units, with a maximum treatment period of 1 day. The product is categorized as a living tissue, incorporating autologous, ex-vivo human fibroblasts and keratinocytes, and is recognized as an orphan drug under designation number EU/3/15/1596.

In this study, the **comparator treatment** is the standard-of-care therapy, which involves the use of autologous split-thickness skin grafts (STSG). This comparator is utilized to evaluate the efficacy and safety of the EHSG-KF in comparison to the traditional method of treating burns. The trial is structured as a Phase IIb, prospective, intra-patient randomized controlled, multicenter study. The primary objective is to assess the efficacy of EHSG-KF based on the ratio of covered surface area to biopsy site/donor site surface area 4 weeks post-grafting. Participant compliance with the treatment regimen is monitored throughout the study to ensure adherence to the dosing schedule and to evaluate the outcomes accurately.

The efficacy of the autologous bio-engineered dermo-epidermal skin substitute (EHSG-KF) will be assessed in a Phase IIb, prospective, intra-patient randomized controlled, multicenter study. The primary endpoint for evaluating efficacy is the ratio of covered surface area to biopsy site/donor site surface area, measured at visit 6, which occurs 28 ± 3 days post-grafting. This comparison will be made between the EHSG-KF and control sites, which utilize meshed split-thickness skin grafts (STSG).

Secondary efficacy endpoints include the percentage of **epithelialization** at visit 8, occurring 90 ± 5 days post-grafting, and the assessment of scar quality at the study areas. Scar quality will be evaluated using the Cutometer® to assess elasticity at visit 10, which is scheduled for 1 year ± 30 days post-grafting. Additionally, the general scar quality will be assessed using the POSAS, a reliable and validated scar assessment tool, also at visit 10. Another secondary efficacy endpoint is the percentage of epithelialization at visit 6.