{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:10:55Z","timestamp":1789099855172,"version":"build-2803163510"},"reference-count":43,"publisher":"Mark Allen Group","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Wound Care"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:sec><jats:title>Objective:<\/jats:title><jats:p>To assess the safety\/tolerability and perform a preliminary efficacy evaluation of a multiple-dosing regimen of recombinant human vascular endothelial growth factor (VEGF<jats:sub>165<\/jats:sub>or rhVEGF; telbermin) applied topically to chronic diabetic neuropathic foot ulcers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method:<\/jats:title><jats:p>Subjects with type 1 or 2 diabetes mellitus were randomised to receive either topical applied telbermin (72\u00b5g\/cm<jats:sup>2<\/jats:sup>) (n=29) or placebo (n=26) treatment to the foot ulcer surface in conjunction with standard ulcer care. Subjects received treatment every 48 hours (maximum three doses per week) for up to six weeks. Weekly 35mm photography, quantitative planimetry and physical examinations documented the ulcer appearance, surface area and stage. Safety endpoints included incidence of clinically significant hypotension, adverse events and ulcer infection. Exploratory efficacy endpoints included percentage reduction in total ulcer surface area, incidence of complete ulcer healing and time to complete ulcer healing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Incidence of adverse events was comparable in the two treatment groups. None of the adverse events were attributed to study drug, and no hypotension was observed as a result of telbermin treatment. Occurrence of infected study ulcers appeared to be balanced between the treatment groups. Positive trends suggestive of potential signals of biological activity were observed for incidence of complete ulcer healing (41.4% telbermin versus 26.9% placebo at day 43 [P=0.39]) and time to complete ulcer healing (25th percentile of 32.5 days telbermin versus 43.0 days placebo [log-rank P=0.13]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>The topical application of telbermin 72\u00b5g\/cm2 three times a week for up to six weeks appeared to be well tolerated. Further studies are required to characterise the safety\/efficacy of telbermin more completely.<\/jats:p><\/jats:sec><jats:sec><jats:title>Declaration of interest:<\/jats:title><jats:p>Paul S. Kwon, Sarah M. Gray and Christopher J. Lynch are employed by Genentech, and own Genentech stock. Tim J. Breen was employed by Genentech before February 2006 and owns Genentech stock. Charles P. Semba was employed by Genentech before December 2007 and owns Genentech stock.<\/jats:p><\/jats:sec>","DOI":"10.12968\/jowc.2008.17.1.27917","type":"journal-article","created":{"date-parts":[[2014,5,23]],"date-time":"2014-05-23T15:59:42Z","timestamp":1400860782000},"page":"30-37","source":"Crossref","is-referenced-by-count":132,"title":["Phase I trial on the safety of topical rhVEGF on chronic neuropathic diabetic foot ulcers"],"prefix":"10.12968","volume":"17","author":[{"given":"J.R.","family":"Hanft","sequence":"first","affiliation":[{"name":"Doctor\u2019s Research Network, South Miami, Florida, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.A.","family":"Pollak","sequence":"additional","affiliation":[{"name":"San Antonio Podiatry Associates, San Antonio, Texas, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Barbul","sequence":"additional","affiliation":[{"name":"Sinai Hospital\/Johns Hopkins University, Baltimore, Maryland, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.van","family":"Gils","sequence":"additional","affiliation":[{"name":"Dixie Regional Medical Center, St George, Utah, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.S.","family":"Kwon","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, California, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.M.","family":"Gray","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, California, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.J.","family":"Lynch","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, California, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.P.","family":"Semba","sequence":"additional","affiliation":[{"name":"SARcode Corporation, San Franciso, US"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.J.","family":"Breen","sequence":"additional","affiliation":[{"name":"Genentech, South San Francisco, California, US"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5130","reference":[{"key":"p_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0891-8422(23)00741-3","volume":"12","author":"Murray H.J.","year":"1995","journal-title":"Clin Podiatr Med Surg"},{"key":"p_2","doi-asserted-by":"publisher","DOI":"10.1086\/424846"},{"key":"p_3","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(98)00181-0"},{"key":"p_4","doi-asserted-by":"publisher","DOI":"10.1126\/science.2479986"},{"key":"p_5","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.240470305"},{"key":"p_7","volume-title":"Senior Statistical Scientist","author":"Gray D"},{"key":"p_8","volume-title":"Chief Medical Officer","author":"Semba MD"},{"key":"p_10","unstructured":"\u25cf Safety outcome measures The primary outcome measure was the incidence of clinically significant hypotension (a drop of \u226535mmHg in systolic blood pressure relative to pre-dose) 60 minutes after application of the study drug during the first week of treatment (days 1, 3 and 5). Selection of this outcome measure was based on preclinical animal studies22-25and clinical studies using systemic VEGF in patients with coronary artery disease in which there appeared to be a dose-related hypotensive effect.26The aetiology of hypotension may involve VEGF-mediated vasodilation secondary to increased nitric oxide release.22,23,27,28"},{"key":"p_25","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2001.6089"},{"key":"p_28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2005.00071.x"},{"key":"p_30","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.134.2.200"},{"key":"p_31","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63754-6"},{"key":"p_33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.21.12607"},{"key":"p_35","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63821-7"},{"key":"p_37","doi-asserted-by":"publisher","DOI":"10.1177\/1534734603256626"},{"key":"p_38","doi-asserted-by":"publisher","DOI":"10.1038\/359843a0"},{"key":"p_43","unstructured":"The high incidence of complete healing in the control group (approximately one-third of subjects) corroborates reports by others of high placebo response rates with standard ulcer care including saline washes, debridement and offloading.29-32Although the study did not meet the primary exploratory efficacy endpoint of reduced total ulcer surface area on day 43, positive trends suggestive of potential signals of biological activity were observed in two key exploratory efficacy outcome measures (incidence of complete ulcer healing and time to complete ulcer healing). Overall, there did not appear to be a trend toward the primary exploratory efficacy outcome measure since the median and mean percent reduction in total ulcer surface area were contradictory. The positive trend for complete healing is notable, considering that the Food and Drug Administration (FDA) considers the incidence of complete ulcer healing as one of the most objective and clinically meaningful wound-healing endpoints for clinical trials.21"},{"key":"p_44","unstructured":"We postulate that the biology of VEGF may provide a potent pathway to accelerate wound healing and closure. As demonstrated by animal model studies, telbermin promotes blood vessel development, tissue growth and repair, and enhances wound closure.6,9-11"},{"key":"p_46","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9610(03)00302-7"},{"key":"p_47","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5694\/j.1326-5377.1967.tb20983.x","volume":"1","author":"Ferrier T.M","year":"1967","journal-title":"Med J Aust"},{"key":"p_48","doi-asserted-by":"publisher","DOI":"10.1177\/1534734605280130"},{"key":"p_50","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.1999.00442.x"},{"key":"p_51","volume-title":"ICH Harmonised Tripartite Guideline E6: Good Clinical Practice: Consolidated Guideline. www.ich.org\/cache\/compo\/475-272-1.html#E6 (accessed on","author":"International Conference","year":"2007"},{"key":"p_52","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.5.855"},{"key":"p_53","doi-asserted-by":"publisher","DOI":"10.1016\/S1067-2516(96)80125-6"},{"key":"p_54","volume-title":"July, 2000 (Updated 2006","author":"Guidance","year":"2007"},{"key":"p_55","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1996.0226"},{"key":"p_56","first-page":"586","volume":"265","author":"Ku D.D.","year":"1993","journal-title":"Am J Physiol"},{"key":"p_58","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.11.2793"},{"key":"p_61","first-page":"1346","volume":"3","year":"2000","journal-title":"Drugs"},{"key":"p_62","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.126179"},{"key":"p_63","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199606000-00011"},{"key":"p_65","first-page":"689","volume":"40","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"p_67","doi-asserted-by":"crossref","unstructured":"multicenter clinical trial. 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