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
James H. Holmes1, Jeffrey W. Shupp2, David Smith3, Victor Joe4, Joshua Carson5, Jeffrey Litt6, Steven Kahn7, Tracee Short8, Leopoldo Cancio9, Julie Rizzo10, Jeffrey Carter11, Kevin Foster12, Janice Smiell13, Angela Lf Gibson14.
1Department of Surgery, Wake Forest University School of Medicine, Winston Salem, NC, USA, 2Department of Surgery, Medstar Washington Hospital Center, Washington DC, WA, USA, 3Department of Plastic Surgery, University of South Florida, Tampa, FL, USA, 4Department of Surgery, University of California at Irvine, Irvine, CA, USA, 5Department of Surgery, University of Florida, Gainesville, FL, USA, 6Department of Surgery, University of Missouri Health Care, Columbia, MT, USA, 7Department of Surgery, University of South Alabama Medical Center, Mobile, AL, USA, 8Department of Surgery, Baton Rouge General Medical Center, Baton Rouge, LA, USA, 9United States Army Institute of Surgical Research, Fort Sam Houston, TX, USA, 10United States Army Institute of Surgical Research, Joint Base, San Antonio, TX, USA, 11Department of Surgery, Louisiana State University School of Medicine, University Medical Center New Orleans, New Orleans, LA, USA, 12Department of Surgery, The Arizona Burn Center at MIHS, Phoenix, AZ, USA, 13Mallinckrodt Pharmaceuticals, Bedminster, NJ, USA, 141Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
BACKGROUND: 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 (M3). This phase 3 study (NCT03005106) evaluated the efficacy and safety of this BRSC in patients with DPT burns.
METHODS: Enrolled patients were 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 M3; and 2) the proportion of patients achieving durable WC of the BRSC treatment site without AG at M3. Safety assessments were performed in all patients. Efficacy was analyzed at M3, and safety and scar follow-up continues to 1 year.
RESULTS: A total of 71 patients were enrolled (mean [SD] age 44  years; mean [SD] %TBSA 12.0 [8.4]). By M3, 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 sites, 2 of whom also required it at their AG sites. Durable WC without AG at the BRSC treatment site was achieved at M3 in 83% of patients compared with 86% of patients at the AG site. The most common BRSC-related adverse event was pruritus, occurring in 11 (15%) patients. All BRSC-related adverse events were mild or moderate in severity.
CONCLUSIONS: This phase 3 study achieved both coprimary endpoints, including significant AG 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.
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