Evaluation of EHSG-KF, a Bilayer Engineered Collagen Hydrogel-Based Skin Graft, in Pediatric Partial Deep Dermal and Full Thickness Burns

The primary objective of this study is to evaluate the **efficacy** and safety of an autologous bio-engineered dermo-epidermal skin substitute (EHSG-KF) compared to meshed split-thickness skin grafts (STSG) in children with partial deep dermal and full-thickness burns. The primary focus is on assessing the ratio of covered surface area to biopsy site/donor site surface area four weeks post-grafting. This is clinically relevant as it directly measures the effectiveness of the skin substitute in covering burn areas, which is crucial for healing and recovery in pediatric burn patients.

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 through various parameters such as infection rates, scar quality using Cutometer® and DSM ColorMeter® at multiple time points, graft take at 6-10 days post-grafting, and the incidence of wound closure at 4, 8, and 12 weeks post-grafting. - Monitoring growth in terms of surface area change between 1 and 3 years post-grafting. - Reporting all observed adverse events. - Conducting quality of life assessments using EQ-5DY and PedsQL. - Analyzing healthcare resource utilization, including direct and indirect healthcare costs.

The clinical trial involves a total of **4 participants** who are children with **partial deep dermal and full-thickness burns**. The study population includes both male and female subjects under the age of 12, reflecting a vulnerable population due to their age and health condition. Participants were selected based on specific criteria, including the presence of deep partial thickness and/or full-thickness burns that necessitate surgical wound coverage. Additionally, it is expected that at least 90 cm² of the wound will remain open at 4 weeks post-burn, despite standard care treatment. The trial does not specify any particular lifestyle considerations such as diet or physical activity. Informed consent was obtained from the patients or their parents/legal representatives, ensuring ethical compliance in the study's conduct.

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 children. The trial compares EHSG-KF to autologous split-thickness skin grafts (STSG). The study is expected to run from October 2017 to March 2028, with participant involvement lasting up to one year post-grafting. The trial employs a **randomized, controlled** design to ensure robust and unbiased results.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age under 12 years, presence of deep partial thickness or full-thickness burns, and the need for surgical wound coverage. Following the initial screening, participants will receive the investigational product, EHSG-KF, and will be monitored through a series of follow-up visits. Key follow-up visits include visit 4 (6-10 days post-grafting) for assessing clinical and microbiologic signs of infection, visit 6 (28 ± 3 days post-grafting) for primary efficacy evaluation, and visit 8 (90 ± 5 days post-grafting) for epithelialization assessment. The end-of-study visit, visit 10, occurs one year ± 30 days post-grafting, focusing on scar quality and elasticity assessments using validated tools such as the POSAS and Cutometer®.

Participants are expected to remain in the study for the full duration unless specific conditions necessitate early termination. These conditions include significant adverse events, non-compliance with study procedures, or withdrawal of consent. 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. Secondary endpoints include epithelialization rates, safety evaluations, and scar quality assessments. The trial aims to provide comprehensive data on the safety and efficacy of EHSG-KF, contributing to the advancement of treatment options for pediatric burn patients.

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 children. 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 not a pediatric formulation and is designated as an orphan drug under the number EU/3/15/1596. The active substances are derived from autologous, ex-vivo human fibroblasts and keratinocytes, 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 serves as the standard-of-care therapy. The trial is designed to evaluate the safety and efficacy of EHSG-KF in comparison to meshed STSG. The primary objective is to assess the efficacy based on the ratio of covered surface area to biopsy site/donor site surface area four weeks post-grafting. Participant compliance will be monitored throughout the study to ensure adherence to the dosing schedule and administration protocol.

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 autologous 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 and the POSAS, a validated scar assessment tool, at visit 10, which is scheduled for 1 year ± 30 days post-grafting. Additionally, epithelialization will also be assessed at visit 6. These endpoints will provide a comprehensive evaluation of the efficacy of EHSG-KF in treating partial deep dermal and full-thickness burns in children.