An open-label single-arm phase 1/2a study to evaluate the safety and exploratory efficacy of a VM202 in patients with Charcot-Marie-Tooth disease 1A

Background: This is the gene therapy trial in patients with Charcot-Marie-Tooth disease type 1A (CMT1A). Intramuscular injections of VM202, a plasmid DNA encoding human hepatocyte growth factor, was investigated for safe and exploratory effective in patients with CMT1A. Methods: This study was an open-label single-arm phase 1/2a 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 exploratory efficacy. CMTNSv2, CMTES, CMTNSv2-R, and CMTES-R 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 decreased with a mean percent decrease of 0.58 (p < 0.05). However, ONLS leg scale and 10-meter walk test were not statistically significant changes. Conclusions: Intramuscular injections of a VM202 appear to be safe and tolerated in CMT1A patients with an exploratory efficacy warrant confirmation in a phase 2b randomized controlled trial. Trial Registration Information: Name of the trial registry (VM202 for CMT1A), Registration number (NCT05361031), URL of the registry (http://www.clinicaltrials.gov) and date of registration (2022–03-31, retrospectively registered).