Objectives: The growing use of NexoBrid, a concentrate of proteolytic enzymes enriched in Bromelain indicated for enzymatic debridement of deep thermal burns, has lead to interest in the treatment of large burns. The objectives of this study were to assess the safety, efficacy and PK (pharmacokinetics) profile of transcutaneous absorption of NexoBrid in patients with deep burns up to 30% TBSA Methods: A multi-center, open label, single-arm study in patients aged 4-70 years old suffering from 4-30% TBSA deep partial (DPT) and full thickness (FT) burns. Patients were treated with either a single 4 hour application of NexoBrid up to 15% TBSA or two consecutive 4 hour applications, each up to 15% TBSA. PK blood samples were collected at 6 time-points in case of a single NexoBrid application, or 7 time-points in case of 2 consecutive NexoBrid applications, up to 48 hours post debridement. Results: Thirty-six patients were enrolled and treated with NexoBrid, 22 with a single application up to 15% TBSA and 14 patients (with a total treatment area of up to 30% TBSA) were treated with two separate NexoBrid applications, each up to 15% TBSA (maximal dose of 60 gr). Patient and wound characteristics can be seen in Table 1. Complete eschar removal was achieved in 89% of patients, in an average of 0.83 days from enrollment (2.16 days from injury). The PK profile in patients treated with 1 or 2 applications is similar; NexoBrid concentration reached Cmax by 2-4 hours and then declined with a mean half life of 12±4.4 hours. Quantifiable serum concentrations were measured through 48 hours after dose administration, and in most cases were below detection limits afterwards. NexoBrid systemic exposure increased with dose and %TBSA, and a small increase in the average PK parameters was observed after the second application. The PK samples were analyzed by 2 different labs using slightly different methods, nevertheless the PK profile obtained was similar (Figure 1). The average time to complete wound closure per patient was 34.2 days. There were 35 adverse events during the study, occurring in 14/36 patients, all of which were not considered treatment-related and were either mild or moderate in intensity. The safety profile in patients treated up to 15% TBSA was comparable to that of patients treated between 15-30% TBSA, with no safety findings associated with increased %TBSA treated or number of applications. Conclusions: NexoBrid use was shown to be safe and the efficacy results are consistent with previous studies. The pharmacokinetic profile following first and second topical applications was comparable, suggesting no concern with accumulation following a second topical application of NexoBrid, up to a total treated area of 30% TBSA.
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