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There is no approved treatment for EB; current standard of care consists of wound and pain management. SD-101 6% is a topical cream containing 6% allantoin that was developed for treating skin lesions in patients with EB. The aim of this phase 3, multicenter, randomized, double-blind, vehicle-controlled study was to assess the efficacy and safety of SD-101 6% cream versus vehicle (0% allantoin) on lesions in patients with EB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eligible patients were\u2009\u22651\u2009month old, had a diagnosis of EB (simplex, recessive dystrophic, or intermediate junctional) and a target wound 10\u201350\u2009cm<jats:sup>2<\/jats:sup>in size that was present for \u226521\u2009days. Patients were randomly assigned to SD-101 6% cream or vehicle, which was applied topically once a day to the entire body for 3\u2009months. Primary efficacy endpoints were time to complete target wound closure within 3\u2009months and the proportion of patients who experienced complete target wound closure within 3\u2009months. Post hoc subgroup analyses were conducted by patient age and in those with body surface area index of total body wound burden \u22655% at baseline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 169 patients were enrolled and randomly assigned to SD-101 6% (<jats:italic>n<\/jats:italic>\u2009=\u200982) or vehicle (<jats:italic>n<\/jats:italic>\u2009=\u200987). Baseline demographics and disease characteristics were similar between treatment groups. There were no statistically significant differences between treatment groups in time to target wound closure (hazard ratio, 1.004; 95% confidence interval [CI] 0.651, 1.549;<jats:italic>P<\/jats:italic>\u2009=\u20090.985) or proportion of patients with complete target wound closure within 3\u2009months (odds ratio [95% CI], 0.733 [0.365, 1.474]; nominal<jats:italic>P<\/jats:italic>\u2009=\u20090.390). A positive trend toward faster wound closure with SD-101 6% versus vehicle was observed in patients aged 2 to &lt;12\u2009years and those with total body wound burden \u22655% at baseline. SD-101 6% cream was well tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SD-101 6% cream for treatment of EB-associated lesions was not more effective than vehicle in shortening the time to complete target wound closure or achieving complete target wound closure within 3\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>,<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02384460\">NCT02384460<\/jats:ext-link>; Date of trial registration, February 13, 2015; First participant enrolled, March 11, 2015.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13023-020-01419-3","type":"journal-article","created":{"date-parts":[[2020,6,23]],"date-time":"2020-06-23T11:03:07Z","timestamp":1592910187000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Efficacy and tolerability of the investigational topical cream SD-101 (6% allantoin) in patients with epidermolysis bullosa: a phase 3, randomized, double-blind, vehicle-controlled trial (ESSENCE study)"],"prefix":"10.1186","volume":"15","author":[{"given":"Amy S.","family":"Paller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Browning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milos","family":"Nikolic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Bodemer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dedee F.","family":"Murrell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willistine","family":"Lenon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Krusinska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen","family":"Reha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hjalmar","family":"Lagast","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay A.","family":"Barth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the ESSENCE Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,23]]},"reference":[{"key":"1419_CR1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/1750-1172-9-76","volume":"9","author":"M El Hachem","year":"2014","unstructured":"El Hachem M, Zambruno G, Bourdon-Lanoy E, Ciasulli A, Buisson C, Hadj-Rabia S, et al. 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An Institutional Review Board\/Independent Ethics Committee reviewed and approved the study design and protocol at each study site, and signed informed consent\/assent was obtained from each patient (or legal guardian if under 18\u2009years of age) prior to entering the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"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. 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\u2019Oreal, Uriage, Takeda, Novartis, Janssen, and Amicus. CB has served on advisory boards for 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. DFM has served as a consultant and investigator for Amicus, Amryt, Castle Creek Pharmaceuticals, and Shire and has conducted her own investigator-initiated randomized controlled trials in recessive dystrophic epidermolysis bullosa and epidermolysis bullosa simplex. EK is a paid consultant of Amicus. AR, HL, and JAB are employees of and hold stock in Amicus.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"158"}}