T5 Preliminary Analysis of a Phase 3 Open-label, Controlled, Randomized Trial Evaluating the Efficacy and Safety of a Bioengineered Regenerative Skin Construct in Patients with Deep Partial-thickness Thermal Burns

Abstract

Abstract Introduction Autograft (AG) is the standard of care for treatment of severe burns. While AG provides effective wound closure (WC), the procedure creates a donor-site wound prone to dyspigmentation, infection, scarring, and pain. In a phase 1b trial, no deep partial-thickness (DPT) wound treated with a bioengineered regenerative skin construct (BRSC) required AG by Day 28 and WC at the BRSC site was achieved in 93% of patients by Month 3 (Holmes et al 2019). This phase 3 study evaluated the efficacy and safety of this BRSC in patients with DPT burns. Methods This phase 3 study (NCT03005106) enrolled patients aged ≥18 years with 3–49% total body surface area (TBSA) thermal burns on the torso or extremities. In each patient, two DPT areas (≤2,000 cm2 total) deemed comparable following excision were randomized to treatment with either cryopreserved BRSC or AG. Coprimary endpoints were 1) the difference in percent area of BRSC treatment site and AG treatment site autografted at 3 months and 2) the proportion of patients achieving durable WC of the BRSC treatment site without AG at 3 months. Safety assessments were performed in all patients. Efficacy was analyzed at 3 months and safety and scar follow-up continues to one year. Results A total of 71 patients were enrolled (mean [SD] age 44 [16] years; mean [SD] %TBSA 12.0 [8.4]). By Month 3, 4.3% (SD 21.6%) of all BRSC-treated area required AG compared with an additional regrafting of 2.1% of all AG-treated area (total 102.1% SD 13.1%; P< .0001). Three patients subsequently required AG at their BRSC site, 2 of whom also required it at their AG sites; Durable WC without autografting at the BRSC treatment site was achieved at Month 3 in 83% of patients compared with 86% of patients at the AG site. The most common BRSC-related adverse event (AE) was pruritus, occurring in 11 (15%) patients. All BRSC-related AEs were mild or moderate in severity. Conclusions This phase 3 study achieved both coprimary endpoints, including significant autograft sparing and durable WC in DPT burns. This BRSC may offer a new treatment for severe burns to reduce or eliminate the need for AG. Applicability of Research to Practice This BRSC has shown clinical benefit in patients with DPT thermal burns, potentially mitigating donor site morbidity. External Funding Stratatech, a Mallinckrodt Company; Funding and technical support for the Phase 3 clinical study were provided by the Biomedical Advanced Research and Development Authority (BARDA), under the Assistant Secretary for Preparedness and Response, within the U.S. Department of Health and Human Services, under Project BioShield Contract No. HHSO100201500027C.