Wound closure in epidermolysis bullosa: data from the vehicle arm of the phase 3 ESSENCE Study

Dedee F Murrell, Amy S Paller, Christine Bodemer, John Browning, Milos Nikolic, Jay A Barth, Hjalmar Lagast, Eva Krusinska, Allen Reha, ESSENCE Study Group, Dedee F Murrell, Amy S Paller, Christine Bodemer, John Browning, Milos Nikolic, Jay A Barth, Hjalmar Lagast, Eva Krusinska, Allen Reha, ESSENCE Study Group

Abstract

Background: Chronic wounds are a fundamental issue for patients with epidermolysis bullosa (EB). Herein, we assess the natural history of wound closure in patients with EB who were randomly assigned to the vehicle-control arm of the multicenter, randomized, double-blind, phase 3 ESSENCE (NCT02384460) trial.

Methods: ESSENCE was designed to assess the efficacy and safety of a topical cream formulation of 6% allantoin (SD-101 6%) vs vehicle (SD-101 0%) in patients ≥1 month old who had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10-50 cm2 present for ≥21 days. Time to complete target wound closure and the proportion of patients with target wound closure over time were analyzed overall and by parameters including patient age and baseline body surface area index (BSAi) of total wound burden (< 5% and ≥ 5%). Changes in BSAi of lesional skin, pain, and itching were also assessed.

Results: The vehicle-control arm included 87 patients. Mean (standard deviation [SD]) time to target wound closure within 3 months was 53.6 (28.6) days, with a range of 14 to 142 days. The proportion of patients with target wound closure increased over time from 7.1% at day 14 to 53.6% at month 3. Mean (SD) changes from baseline in BSAi of total wound burden and BSAi of lesional skin at month 3 were -2.3% (6.3) and -5.0% (13.5) of total body coverage, respectively. Reductions in pain and itching were observed at day 7 and maintained for 3 months. Faster healing times and a greater proportion of patients with wound closure were observed in patients aged 1 month to < 2 years; those with wounds < 30 days old, and in those with BSAi of total body wound burden < 5%.

Conclusions: Treatment response observed in the vehicle-control arm of the ESSENCE study was unexpectedly high and may have been due to unforeseen benefits of vehicle or enhanced wound care provided by the clinical trial staff. These observations will help inform the study design of future trials in patients with EB.

Trial registration: ClinicalTrials.gov , NCT02384460 ; Date of registration: February 13, 2015; First participant enrollment: March 11, 2015.

Keywords: Epidermolysis bullosa; Natural history; Wound closure.

Conflict of interest statement

DFM has served as a consultant and investigator for Amicus, Amryt, Castle Creek Pharma, and Shire and has conducted her own investigator-initiated randomized controlled trials in recessive dystrophic epidermolysis bullosa and epidermolysis bullosa simplex. ASP has served as an investigator (uncompensated) for Amicus, Castle Creek Pharmaceuticals, Lenus Therapeutics and Shire, and as a consultant with honorarium for Castle Creek Pharmaceuticals, Lenus Therapeutics, and MEDACorp. CB has served on advisory boards for Pfizer and Sanofi, as a consultant for Expanscience, as an investigator (uncompensated) for Amicus, as a speaker for La Roche-Posay and Expanscience, and has received honoraria from Celgene and Novartis. JB has served as an investigator for Amicus, Galderma, Valeant, Patagonia, and Regeneron and as a speaker for Medimetriks and Promius. MN has received honoraria from Meda/Mylan, Medis, La Roche-Posay/L’Oreal, Uriage, Takeda, Novartis, Janssen, and Amicus. JAB, HL, and AR are employees of and hold stock in Amicus. EK is a paid consultant to Amicus.

Figures

Fig. 1
Fig. 1
Change in (a) lesional skin BSAi, (b) total body wound burden BSAi over 3 months. BSAi body surface area index; EB epidermolysis bullosa; SE standard error. Analysis excluded patients with missing values, resulting in variability in patient numbers at each visit
Fig. 2
Fig. 2
Change in (a) pain and (b) itch scores over 3 months. SE standard error. Analyses excluded patients with missing data
Fig. 3
Fig. 3
Proportion of vehicle-treated patients with complete target wound closure within 3 months by (a) patient age, (b) target wound age, (c) BSAi of total body wound burden, and (d) EB type. BSAi body surface area index; d day; EB epidermolysis bullosa; y year

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