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

Brief Summary

Detailed Description

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. All Participants will receive sixteen (16) 0.5-mL intramuscular injections of Engensis or Placebo in each calf gastrocnemius muscle at each of two Visits during two Treatment Cycles: Treatment Cycle 1 on Day 0 and Day 14, and Treatment Cycle 2 on Day 90 and Day 104. At 2 hours (± 1 hour) after completion of intramuscular injections of Engensis or Placebo on Days 0 and 14 and Days 90 and 104, vital signs and blood draw for cytokine levels will be performed. Treatment-emergent adverse event assessment, including injection site reactions, will start as of randomization (Day 0) and continue throughout the study. Follow-up Study Visits will be conducted on Days 28, 60, 150, and 180 or early termination. Vital signs will be recorded at all Study Visits. At the Day 180 Visit (end of study), the following assessments will be conducted: the full Brief Pain Inventory for Diabetic Peripheral Neuropathy (performed for 7 days prior to the Day 180 Visit), Michigan Neuropathy Screening Instrument, Bedside Sensory Testing, Patient Global Impression of Change and the quality of life assessments (36-item Short Form Health Survey and European Quality of Life Health Utilities Index, urine drug analysis, retinal fundoscopy, physical examination, concomitant medications and procedures, and anti-Hepatic Growth Factors antibodies. Blood will be drawn for determination of serum chemistry, lipid profile, pregnancy status, hematology, and Hemoglobin A1c levels. The purpose of this study is to assess the efficacy and safety of Engensis compared to Placebo as measured by changes in the means of the Average Daily Pain Scores of the full Brief Pain Inventory for Diabetic Peripheral Neuropathy, selected blood cytokines, Bedside sensory testing, and assessments of injection site reactions, physical examination, laboratory assessments, vital signs, treatment emergent Adverse events, and serious adverse events. Study and Treatment Duration: Screening will occur up to 52 days prior to Baseline (Day 0) and Participants will be followed from Day 0, the day of first Study Injections, to Day 180/Early termination. Visit Frequency: Consented Participants will be seen and evaluated for enrollment during Screening (up to 52 days prior to Baseline, Day 0). There are 8 visits to the Clinical Site during the study from Day 0 to Day 180 for Study Injections and follow-up. Intervention Groups and Duration: Two treatment groups of Participants (Engensis or Placebo) will be in the study for 180 days. Number of Participants (N = 152 to approximately 250): The target sample size is a minimum of 152 Participants and the maximum sample size is 250 Participants based on the proposed adaptive design analysis. The final sample size of Participants to be enrolled and evaluated will be determined by the independent Data Monitoring Committee. An interim analysis will be conducted after approximately 50% of Participants in the target sample (i.e., 76 Participants) have completed the primary efficacy endpoint at Day 180 or have withdrawn prematurely. The Data monitoring committee will make a recommendation based on an unblinded (comparative) power analysis.

Primary Outcomes

Secondary Outcomes

• Efficacy of Engensis on Worst Pain in Painful Diabetic Peripheral Neuropathy in Feet and Legs by Comparing Change From Baseline (Day 0) in Worst Pain Score From Brief Pain Inventory for Diabetic Peripheral Neuropathy to Day 180 Compared to Placebo(180 days)
• Efficacy of Engensis Reducing Painful Diabetic Peripheral Neuropathy in Feet and Legs by Determining a ≥ 50% Reduction in the Average Daily Pain Score From Baseline to Day 180 Using the Brief Pain Inventory With Participants Diabetic Peripheral Neuropathy(180 days)
• Safety of Engensis in Painful Diabetic Peripheral Neuropathy in Feet and Legs Comparing Incidence of Adverse and Serious Adverse Events, Incidence of Injection Site Reactions, and Incidence of Clinically Significant Laboratory Values to Placebo(180 days)
• To Evaluate the Possibility of Cellular Responses to Engensis(104 days)
• To Evaluate the Possibility of Humoral Responses to Engensis - Anti-Hepatic Growth Factor(Days 0, 60, 90, 150 and 180)