An Adaptive, Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Engensis in Participants With Painful Diabetic Peripheral Neuropathy

Overall Design VMDN-003-2 is an adaptive Phase 3, double-blind, randomized, placebo-controlled, multicenter study designed to assess the efficacy and safety of Engensis (containing the active pharmaceutical ingredient VM202) in Participants with painful Diabetic Peripheral Neuropathy. Following completion of the informed consent process, Screening activities (during 45 days [from Day -52 to Day -7] prior to Day 0) will determine which Participants meet all-but-one eligibility criteria, which are assessed by an adjudication procedure, followed by completion of a 7-day eDiary prior to Day 0. Eligible participants will be enrolled and randomly assigned in a double-blind fashion and in a 1:1 ratio on Day 0 to either Engensis or Placebo. During Screening, medical history and familial cancer history, demographics, vital signs, height, body mass index, waist size, physical examination, retinal fundoscopy (by an ophthalmologist), 12-lead electrocardiogram, ultrasound of the right and left gastrocnemius muscles (to guide Study Injections), laboratory assessments, estimated glomerular filtration rate, Hemoglobin A1c levels, viral screening, a record of all concomitant medications and procedures, urine drug analysis, and urine pregnancy test for females of childbearing potential will be conducted.

In addition, the following procedures will be conducted during Screening: Hospital Anxiety and Depression Scale, Accurate Pain Reporting and Placebo Response Reduction, Michigan Neuropathy Screening Instrument, and cancer screening tests.

During 7 days before Day 0 and randomization, Participants must complete the full Brief Pain Inventory for Diabetic Peripheral Neuropathy on an eDiary for determining the Average Daily Pain Scores for at least 5 out of the 7 days. Adverse event assessments will start upon completion of the consent process at the start of Screening.

At any time prior to dosing on Day 0, Bedside Sensory Testing should be administered.

Following randomization, and prior to the first intramuscular injections of Engensis or Placebo on Day 0, the partial Brief Pain Inventory for Diabetic Peripheral Neuropathy, , and quality of life instruments will be completed. Blood will be collected for testing of selected cytokines, anti-Hepatic growth factor antibodies, and laboratory assessments.