{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:24:27Z","timestamp":1784201067793,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Wound Journal"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To evaluate the status of a 7\u2010month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent\u2010to\u2010Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a <jats:italic>t<\/jats:italic>\u2010test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N\u2009=\u200944), there was a positive trend toward closure in the VM202 group from 3 to 6\u2009months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound\u2010closing effects at month 6 (<jats:italic>P<\/jats:italic>\u2009=\u2009.0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (<jats:italic>P<\/jats:italic>\u2009=\u2009.0391, .0391, and .0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (<jats:italic>P<\/jats:italic>\u2009=\u2009.03 for all points). A potentially clinically meaningful 0.15 increase in Ankle\u2010Brachial Index was observed in the VM202 group at day 210 in the ITT population (<jats:italic>P<\/jats:italic>\u2009=\u2009.0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites.<\/jats:p>","DOI":"10.1111\/iwj.14226","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T21:40:05Z","timestamp":1685050805000},"page":"3531-3539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Gene therapy for diabetic foot ulcers: Interim analysis of a randomised, placebo\u2010controlled phase 3 study of <scp>VM202<\/scp> (<scp>ENGENSIS<\/scp>), a plasmid <scp>DNA<\/scp> expressing two isoforms of human hepatocyte growth factor"],"prefix":"10.1111","volume":"20","author":[{"given":"Emerson","family":"Perin","sequence":"first","affiliation":[{"name":"Director of the Center for Clinical Research Texas Heart Institute  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey","family":"Loveland","sequence":"additional","affiliation":[{"name":"Podiatric Surgery Reno Foot and Ankle  Reno Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Caporusso","sequence":"additional","affiliation":[{"name":"Complete Family Foot Care Futuro Clinical Trials, LLC  McAllen Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyaandi","family":"Dove","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics UT Health San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Motley","sequence":"additional","affiliation":[{"name":"Medical Director, Podiatry Acclaim Bone &amp; Joint Institute  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Sigal","sequence":"additional","affiliation":[{"name":"Podiatric Medicine Foot and Ankle Clinic  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mher","family":"Vartivarian","sequence":"additional","affiliation":[{"name":"Podiatry UCSF Health  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Oliva","sequence":"additional","affiliation":[{"name":"Division of Podiatry Mercy Hospital  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Surgery Keck School of Medicine of the University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the VMNHU\u2010003 study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2016.1231932"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67698-2"},{"key":"e_1_2_10_5_1","unstructured":"SnyderRJ KirsnerRS WarrinerRA3rd LaveryLA HanftJR SheehanP.Consensus Recommendations on Advancing the Standard of Care for Treating Neuropathic Foot Ulcers in Patients with Diabetes HMP Communications.2010."},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13047-020-00383-2"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.12404"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13680"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2017.11.005"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13569"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.22.5.692"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00280.2008"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.21"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2010.101"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2483071579"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26704-x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.08.054"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201800476R"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2015.110"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.10.017"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1614"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30012-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.2758"}],"container-title":["International Wound Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/iwj.14226","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T06:23:44Z","timestamp":1754288624000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/iwj.14226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":22,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1111\/iwj.14226"],"URL":"https:\/\/doi.org\/10.1111\/iwj.14226","archive":["Portico"],"relation":{},"ISSN":["1742-4801","1742-481X"],"issn-type":[{"value":"1742-4801","type":"print"},{"value":"1742-481X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,25]]},"assertion":[{"value":"2023-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}