(CR-030) Results from a Phase 2 multicenter, randomized, placebo controlled, adaptive design study performed to evaluate safety and efficacy of Bromelain-based enzymatic debridement agent (BBD) in debridement of Venous Leg Ulcers (VLUs)

Robert Snyder, DPM

Introduction: Debridement represents a key step in the management of chronic wounds and is considered a basic necessity to induce wound bed preparation that leads to tissue repair. Use of novel therapies that specifically remove the non-viable tissues, is a promising strategy for improving patient outcomes. BBD is currently in clinical development for debridement of chronic wounds. Study objectives were to assess safety and efficacy of BBD in patients with VLUs.

Methods: 120 patients with 2-100cm² VLUs containing ≥50% non-viable tissue were randomized to 3 arms: BBD, Gel Vehicle (GV, placebo) or Non-surgical standard of care (NSSOC, commercially approved products for debridement) at a ratio 3:3:2. Patients were treated with up to 8 daily applications of BBD or GV or with unlimited number of NSSOC treatments (in accordance with its label) and then continued follow-up for up to 12 weeks. Wounds were clinically assessed for complete debridement and wound size was measured by Planimetry system in each clinic visit.

Results: Patients treated with BBD had a statistically significant higher incidence of complete debridement within up to 8 applications compared to GV (BBD=63% vs. GV=30%, p=0.004), and to NSSOC (13%, p< 0.001, post-hoc). The estimated median time to complete debridement was significantly shorter: BBD=9 vs. NSSOC=59 days (p=0.016). Patients treated with BBD demonstrated higher incidence of ≥75% granulation tissue at the end of treatment compared to GV (p< 0.0001), and demonstrated a higher incidence of “wound bed prepared” with complete debridement and complete granulation, compared to GV (p=0.01, post-hoc) and NSSOC (p=0.0002, post-hoc). Non-inferiority was established between study arms in the rates of complete wound closure with 32.6%, 27.9% and 26.7% closure achieved for BBD, GV & NSSOC, respectively. The most common adverse events were local. No serious adverse reactions related to BBD were reported. BBD is safe and well tolerated in VLU patients.

Discussion: The data shows that BBD is a safe and effective product. BBD is significantly more effective and faster than NSSOC and GV in debridement of VLU and in promoting the formation of a healthy granulation tissue, and has no deleterious effect on occurrence or time to wound healing.