A phase 1/2a, open label study to evaluate the safety and efficacy of a plasmid DNA encoding human hepatocyte growth factor in patients with Charcot-Marie-Tooth disease 1A

Abstract

Background This is the first gene therapy trial in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). Intramuscular injectionsof VM202, a plasmid DNA encoding human hepatocyte growth factor, was safe, tolerable and potentially effective in patients with CMT1A. Methods This study was a phase 1/2a, nonrandomized controlled trial. Thirteen patients with CMT1A were screened, and 12 consented and enrolled between September 2020 and November 2020. Patients received intramuscular injections of 14 mg of VM202 at baseline, and on days 14, 90, and 104 in both legs. Safety evaluations and clinical assessments using the CMT neuropathy score version 2 (CMTNSv2), CMT examination score (CMTES), Rasch-modified CMTNSv2 (CMTNSv2-R), Rasch-modified CMTES (CMTES-R), functional disability scale (FDS), overall neuropathy limitation score, and 10-meter walk test were performed throughout a 270-day follow-up period. A Wilcoxon signed-rank test was used for statistical comparisons of continuous variables. Results The primary objective of this study was to assess the safety and tolerability of intramuscular injections of VM202 in patients with CMT1A. All participants tolerated VM202 well, without any serious adverse events related to the study drug. The secondary objective was to evaluate potential therapeutic efficacy. CMTNSv2, CMTES, CMTNSv2-R, and CMTES-R significantly decreased between baseline and day 270 with mean decreases of 2.17, 2.50, 2.08, and 2.33 points, respectively (p < 0.01). Also FDS significantly decreased with a mean percent decrease of 0.58 (p < 0.05). ConclusionsIntramuscular injections of VM202 appear to be safe and well tolerated in CMT1A patients with potentially encouraging clinical results.