31 A phase 3 open-label, controlled, randomized trial evaluating the efficacy and safety of a bioengineered allogeneic cellularized construct in patients with deep partial-thickness thermal burns
Authors: Gibson Angela L F , Holmes James H , Shupp Jeffrey W , Smith David , Joe Victor , Carson Joshua , Litt Jeffrey , Kahn Steven , Short Tracee , Cancio Leopoldo , Rizzo Julie , Carter Jeffrey E , Foster Kevin , Allen-Hoffmann B Lynn 
Published: April 2021

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 pain and scarring. In a phase 1b trial, no deep partial-thickness (DPT) wound treated with a bioengineered allogeneic cellularized construct (BACC) required AG by Day 28 and WC at the BACC site was achieved in 93% of patients by Month (M) 3. This phase 3 study (NCT03005106) evaluated the efficacy and safety of this BACC in patients with DPT burns.

Methods
Enrolled patients were aged ≥18 years with 3–49% 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 BACC or AG. Coprimary endpoints were 1) the difference in percent area of BACC treatment site and AG treatment site autografted at M3 and 2) the proportion of patients achieving durable WC of the BACC treatment site without AG at M3. Ranked secondary endpoints were: 1) the difference between BACC and AG donor sites in average donor site pain intensity through Day 14; 2) the difference between BACC and AG donor site cosmesis at M3; and 3) the difference between BACC and AG treatment site cosmesis at M12. Safety assessments were performed in all patients through M12.

Results
Seventy-one patients were enrolled. By M3, there was a 96% reduction in mean percent area of BACC treatment sites that required AG, compared with AG treatment sites (4.3% vs 102.1%, respectively; P&lt;.0001). BACC treatment resulted in durable WC at M3 without AG in 92% (95% CI: 85.6, 98.8; 59/64) of patients for whom data was available. By M3, mean donor site Patient and Observer Scar Assessment Scale (POSAS) observer total score (±SD) was significantly lower (more like normal skin) for BACC donor sites compared with AG donor sites (6.3 ± 1.71 vs 16.3 ± 7.71; P&lt;.0001). At M12, mean POSAS observer total score (±SD) was 15.6 (± 8.34) for BACC treatment sites compared with 16.3 (± 9.41) for AG treatment sites (P=.4268). The most common BACC-related adverse event (AE) was pruritus, which occurred in 11 (15%) patients. All BACC-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. Both donor site pain and donor site cosmesis were favorable outcomes of significantly reduced use of AG in BACC-treated patients. M12 POSAS for BACC did not differ significantly from AG. This BACC may offer a new treatment for severe burns to reduce or eliminate the need for AG.

Applicability of Research to Practice
This BACC 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.