{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:06:20Z","timestamp":1792166780531,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>VM202 is a plasmid DNA encoding two isoforms of hepatocyte growth factor (HGF). A previous phase II study in subjects with painful diabetic peripheral neuropathy (DPN) showed significant reductions in pain. A phase III study was conducted to evaluate the safety and efficacy of VM202 in DPN. The trial was conducted in two parts, one for 9\u00a0months (DPN 3\u20101) with 500 subjects (VM202: 336 subjects; and placebo: 164) and a preplanned subset of 101 subjects (VM202: 65 subjects; and placebo: 36) with a noninterventional extension to 12\u00a0months (DPN 3\u20101b). VM202 or placebo was administered to calf muscles on days 0 and 14, and on days 90 and 104. The primary end point in DPN 3\u20101 was change from baseline in the mean 24\u2010h Numerical Rating Scale (NRS) pain score. In DPN 3\u20101b, the primary end point was safety, whereas the secondary efficacy end point was change in the mean pain score. VM202 was well\u2010tolerated in both studies without significant adverse events. VM202 failed to meet its efficacy end points in DPN 3\u20101. In DPN 3\u20101b, however, VM202 showed significant and clinically meaningful pain reduction versus placebo. Pain reduction in DPN 3\u20101b was even greater in subjects not receiving gabapentin or pregabalin, confirming an observation noted in the phase II study. In DPN 3\u20101b, symptomatic relief was maintained for 8\u00a0months after the last injection suggesting that VM202 treatment might change disease progression. Despite the perplexing discrepancy between the two studies, the safety and long\u2010lasting pain\u2010relieving effects of VM202 observed in DPN 3\u20101b warrant another rigorous phase III study.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"box\" position=\"anchor\"><jats:caption><jats:title>Study Highlights<\/jats:title><\/jats:caption><jats:p>\n<jats:list list-type=\"simple\">\n\n<jats:list-item><jats:p>\n<jats:bold>WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?<\/jats:bold>\n<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p>Current therapies for painful diabetic peripheral neuropathy (DPN) are palliative and do not target the underlying mechanisms. Moreover, symptomatic relief is often limited with existing neuropathic pain drugs. Thus, there is a great medical need for safer and effective treatments for DPN.\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p><jats:bold>WHAT QUESTION DID THIS STUDY ADDRESS?<\/jats:bold><\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Can nonviral gene delivery of hepatocyte growth factor reduce pain in patients with DPN and potentially modify progression of the disorder?\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p><jats:bold>WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?<\/jats:bold><\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>Nonviral gene therapy can be used safely and practically to treat DPN.\n<jats:list list-type=\"simple\">\n<jats:list-item><jats:p><jats:bold>HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?<\/jats:bold><\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p>As the first gene medicine to enter advanced clinical trials for the treatment of DPN, this study provides the proof of concept of an entirely new potential approach to the disorder.<\/jats:p><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/cts.12977","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T14:09:58Z","timestamp":1611065398000},"page":"1176-1184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Gene therapy for diabetic peripheral neuropathy: A randomized, placebo\u2010controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor"],"prefix":"10.1111","volume":"14","author":[{"given":"John A.","family":"Kessler","sequence":"first","affiliation":[{"name":"Department of Neurology Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Shaibani","sequence":"additional","affiliation":[{"name":"Nerve and Muscle Center of Texas Texas Medical Center Houston Texas 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