Gene Therapy for Painful Diabetic Neuropathy

A Phase I/II, Open Label, Dose-Escalation Study to Assess the Safety and Tolerability of Engensis (VM202) in Patients With Painful Diabetic Peripheral Neuropathy

The purpose of this open label, Phase I/II, dose-escalation, 3-cohort, multicenter, 12-month study, is to assess the safety and tolerability of injecting Engensis (VM202) in the leg muscle in patients with painful diabetic peripheral neuropathy (DPN). The study will also assess the potential of VM202 to reduce the pain associated with diabetic peripheral neuropathy.

Study Overview

• Status: Completed
• Conditions: Painful Diabetic Peripheral Neuropathy
• Intervention / Treatment: Biological: VM202

Detailed Description

Peripheral neuropathy is a serious complication of diabetes. This form of neuropathy carries a high risk of pain, trophic changes and autonomic dysfunction.

Currently, there are no approved drugs or interventional strategies known to halt or reverse the progression of painful diabetic peripheral neuropathy (DPN). Treatments target pain reduction, physical function improvement, reduction of psychological distress, and quality of life improvements.

There is currently no effective treatment for diabetic neuropathy, and good glycemic control is the only way to minimize the risk of occurrence. Clearly, it would be desirable to prevent, impede, or reverse the disrupting and often life-threatening manifestations of peripheral neuropathy by stimulating growth or regeneration of peripheral nerve axons.

The purpose of this open label, dose-escalation, 3-cohort study is to assess the safety and tolerability of injecting Engensis (VM202) in the leg muscle in patients with painful diabetic peripheral neuropathy. The study will also assess the potential of VM202 to reduce the pain associated with diabetic peripheral neuropathy.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years to 75 years
• Documented history of Type I or II diabetes with current treatment control (glycosylated hemoglobin A1c of ≤ 10.0%)
• Diagnosis of painful diabetic peripheral neuropathy in both lower extremities
• The physical examination component of the Michigan Neuropathy Screening Instrument Score (MNSI) is ≥ 3 at Screening
• Visual analog scale (VAS) score of ≥ 4 cm at Screening (0 cm = no pain - 10 cm worst imaginable pain)
• Stable treatment of diabetes for at least 3 months with no anticipated changes in medication regimen, and no new symptoms associated with diabetes
• Lower extremity pain for at least 6 months
• If female of childbearing potential, negative pregnancy test at screening and using acceptable method of birth control during the study.

Exclusion Criteria:

• Peripheral neuropathy caused by condition other than diabetes;
• Other pain more severe than neuropathic pain;
• Progressive or degenerative neurological disorder;
• Myopathy;
• Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease);
• Active infection;
• Chronic inflammatory disease (e.g. Crohn's, Rheumatoid Arthritis)
• Positive HIV or HTLV at Screening
• Positive Hepatitis B or C as determined by Hepatitis B core antibody (HBcAB), antibody to Hepatitis B antigen (IgG and IgM; HbsAB), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV), at Screening or known immunosuppression or on chronic treatment with immunosuppressive drugs, chemotherapy or radiation therapy
• Stroke or myocardial infarction within last 6 months;

• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination:

  • Cataract surgery within 6 months of trial;
  • Vascular lesions of the anterior segment of the eye (infection or ulceration of the cornea, rubeotic glaucoma, etc);
  • Vascular lesions of the posterior segment of the eye or proliferative retinopathy, macular edema, s/p photocoagulation for macular edema or proliferative retinopathy; sickle cell retinopathy, ischemic retinopathy due to retinal venous stasis or carotid artery disease;
  • Choroidal angiogenesis; and
  • Large elevated choroidal nevi, choroidal vascular tumors (choroidal hemangioma), or melanomas.
• Specific laboratory values at Screening including: Hemoglobin < 9.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, Creatinine > 2.0 mg/dL; GFR < 50, AST and/or ALT > 2 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary;
• Use of gamma-linolenic acid (GLA), alpha lipoic acid or any other high dose dietary antioxidant supplement for symptomatic relief of DPN;
• Uncontrolled hypertension as defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at baseline/screening evaluation;
• Patients with history of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence);
• Malignant tumors or abnormal screening test suspicious for cancer, or patients in whom screening exams indicate possible occult malignancy unless malignancy has been ruled out. Patients with family history of colon cancer in any first degree relative unless they have undergone a colonoscopy in the last 12 months with negative findings;
• Elevated PSA unless prostate cancer has been excluded;
• Subjects requiring > 81 mg daily of acetylsalicylic acid; If > 81 mg are taken at screening, subjects may be enrolled if willing/able to switch to another medication;
• Major psychiatric disorder in past 6 months;
• History of drug or alcohol abuse / dependence in the past 2 years;
• History of recent tobacco abuse (within past 5 years);
• BMI > 38 kg/m2;
• Use of an investigational drug or treatment in past 12 months; and
• Unable or unwilling to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Two divided doses of VM202 injected into the calf muscle on Day 0 and Day 14 for a total dose of 4 mg.	Biological: VM202; Intramuscular injections in the calf on Day 0 and Day 14.
Experimental: Cohort 2; Two divided doses of VM202 injected into the calf muscle on Day 0 and Day 14 for a total dose of 8mg.	Biological: VM202; Intramuscular injections in the calf on Day 0 and Day 14.
Experimental: Cohort 3; Two divided doses of VM202 injected into the calf muscle on Day 0 and Day 14 for a total dose of 16mg.	Biological: VM202; Intramuscular injections in the calf on Day 0 and Day 14.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg	Treatment-emergent adverse events are any adverse events that occurred after the first dose of Engensis (VM202). This is a dose escalation study. Cohorts of increasing dose will be enrolled sequentially. Dose escalation decisions (permission to treat at higher doses) will be made by the Data Safety Monitoring Board based on review of adverse events and on the occurrence of dose limiting toxicities in each cohort. The decision to proceed to the next higher dose cohort will be made according to the scheme described in the protocol.	Day 0 to Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Visual Analog Scale Pain Scores	Percent change in median Visual Analog Scale Pain Scores from baseline (Day 0). The Visual Analog Scale Pain scoring instrument is a 10-cm line, oriented horizontally, with the left end (0 cm, is 0 Percent) indicating "no pain" and the right end (10 cm, is 100 percent) representing "pain as bad as it can be". The Change from Baseline of the Visual Analog Scale Pain Score is the difference between the Day 0 and the Days 90, 180 and 365 scores. A negative difference in the Change from Baseline of the Visual Analog Scale Pain Scores, indicates an improvement (reduction of pain severity) of the treated groups Visual Analog Score.	Days 0, 90, 180, and 365

Collaborators and Investigators

• Sponsor: Helixmith Co., Ltd.
• Investigators: Principal Investigator: John Kessler, M.D., Northwestern Memorial Hospital

Publications and helpful links

General Publications

• Ajroud-Driss S, Christiansen M, Allen JA, Kessler JA. Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy. Mol Ther. 2013 Jun;21(6):1279-86. doi: 10.1038/mt.2013.69. Epub 2013 Apr 23.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: October 24, 2009
• First Submitted That Met QC Criteria: October 24, 2009
• First Posted (Estimated): October 27, 2009

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: diabetes; Diabetic; Neuropathy; Peripheral
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Diabetes Mellitus
• Other Study ID Numbers: VMDN-001/G