Extension of Phase 3 Gene Therapy for Painful Diabetic Neuropathy

Long-term, Prospective, Non-interventional, Extension of a Phase III, Randomized, Placebo-controlled, Multicenter Study to Assess the Safety & Efficacy of Engensis (VM202) in Subjects With Painful Diabetic Peripheral Neuropathy

The purpose of this study is to explore the overall safety profile and durability of efficacy of Engensis (VM202) in painful diabetic peripheral neuropathy.

All subjects still in follow-up for the VMDN-003 study or who have completed the Day 270 visit within the prior 90 days will be approached to enroll in the long-term safety extension study.

Study Overview

• Status: Completed
• Conditions: Diabetic Neuropathy, Painful; Painful Diabetic Neuropathy
• Intervention / Treatment: Genetic: Long-Term Follow-Up of Patients who Received Engensis (VM202); Drug: Long-Term Follow-Up of Patients who Received Placebo

Detailed Description

In the phase III VMDN-003 study, subjects received 2 treatments of either Engensis (VM202) or placebo administered as intramuscular injections into bilateral calves on Days 0 and 14, and Days 90 and 104. Primary efficacy was evaluated 90 days following the first injection. The growth potential for Hepatocyte Growth Factor make long-term follow-up important both for safety and efficacy: in order for Engensis to be a candidate for chronic treatment of Painful Diabetic Peripheral Neuropathy, it must be demonstrated not to induce unexpected adverse events with repeated dosing; and the potential for reversal or stabilization of diabetic neuropathy using only one or two treatments of Engensis may make it especially attractive compared to current treatments which must be taken daily for the duration of the disease. A safety extension to the VMDN-003 study is therefore warranted.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Clinical Trials, Inc.
  • California
    • Sacramento, California, United States, 95821
      • Northern California Research
    • San Francisco, California, United States, 94115
      • Center for Clinical Research
    • Santa Monica, California, United States, 90404
      • Neurological Research Institute
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida McKnight Brain Institute
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • The Brigham and Women's Hospital
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurology Associates, P.A.
  • Texas
    • Houston, Texas, United States, 77030
      • Nerve and Muscle Center of Texas
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • EVMS (Eastern Virginia Medical School)
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Were randomized and dosed in the VMDN-003 study
2. Received all intramuscular injections of study drug on Days 0, 14, 90, and 104 in the VMDN-003 study
3. Were in follow-up for the VMDN-003 study or had completed Day 270 within the last 90 days prior to signing consent

Exclusion Criteria:

1. Were using an investigational drug or treatment
2. Were unable or unwilling to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Subjects who received Placebo; Placebo, vehicle	Drug: Long-Term Follow-Up of Patients who Received Placebo; No study drug is administered in this study. Patients who received Placebo in the previous trial (VMDN-003) will remain blinded and were evaluated in this trial for long-term safety and efficacy.
Experimental: Subjects who received Engensis (VM202); VM202, Engensis	Genetic: Long-Term Follow-Up of Patients who Received Engensis (VM202); No study drug is administered in this study. Patients who received Engensis (VM202) in the previous trial (VMDN-003) will remain blinded and were evaluated in this trial for long-term safety and efficacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term Safety for Engensis Versus Placebo	Long-term (6 months) safety in terms of the incidence of Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events for Subjects who received Engensis or Placebo (in the prior VMDN-003 study)	Baseline through Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo	The Average 24-hour Pain Score was obtained from the Daily Pain and Sleep Interference Diary. The change in the Average 24-hour Pain Score was determined from baseline (Day 0 of Study VMDN-003) to the Day 365 visit. The Average 24-hour Pain Score is an 11-point numerical scale with scores from 0 (No Pain) to 10 (Worst Possible Pain).	Baseline to the Day 365
Change in the Average 24-hour Pain Score From Day 270 to Day 365 for Engensis Versus Placebo	The Average 24-hour Pain Score is from the Daily Pain and Sleep Interference Diary. The change in the Average 24-hour Pain Score was determined for Day 270 to Day 365. The Average 24-hour Pain Score is an 11-point numerical scale with scores from 0 (No Pain) to 10 (Worst Possible Pain).	Day 270 to Day 365
Patient's Global Impression of Change at the Day 365 Visit for Engensis Versus Placebo	The Patient's Global Impression of Change was completed by subjects (self-administered) at the Day 365 visit. The subject evaluated how his/her overall status had changed since the start of the study using a 7-point Patient's Global Impression of Change questionnaire scale, where 1 = Very Much Improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse. The Outcome Measure was the Patient's Global Impression of Change Categories of Scores as follows: 1 = Very Much Improved or Much Improved, 0 = Minimally Improved/Worsened or No Change, and -1 = Much Worse or Very Much Worse.	At the Day 365 visit
Subgroup Analysis of the Change in the Average 24-hour Pain Score From Baseline (Day 0 of Study VMDN-003) to Day 365 for Engensis Versus Placebo for Subjects Without Gabapentin and/or Pregabalin Use at Baseline	The Average 24-hour Pain Score was obtained from the Daily Pain and Sleep Interference Diary and the change in the Average 24-hour Pain Score from baseline (Day 0 of Study VMDN-003) to the Day 365 follow-up was determined. The Average 24-hour Pain Score is an 11-point numerical scale with scores from 0 (No Pain) to 10 (Worst Possible Pain).	Baseline to Day 365

Collaborators and Investigators

• Sponsor: Helixmith Co., Ltd.
• Investigators: Principal Investigator: John A. Kessler, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2019
• Primary Completion (Actual): July 24, 2019
• Study Completion (Actual): July 24, 2019

Study Registration Dates

• First Submitted: February 22, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: neuropathy; foot pain; diabetic; shooting pain; burning pain; pins and needles pain; ViroMed; VM202; Engensis; Helixmith
• Additional Relevant MeSH Terms: Neurologic Manifestations; Endocrine System Diseases; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetes Mellitus; Diabetes Complications; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain; Diabetic Neuropathies
• Other Study ID Numbers: VMDN-003b

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No