Phase 3 Gene Therapy for Painful Diabetic Neuropathy

Inclusion Criteria

• Age ≥ 18 years to ≤ 75 years
• Documented history of type I or II diabetes with current treatment control (HbA1c of ≤ 10.0% at Screening) and currently on medication for diabetes (oral, injectable, and/or insulin)
• No significant changes anticipated in diabetes medication regimen
• No new symptoms associated with diabetes within the last 3 months prior to study entry
• Diagnosis of painful diabetic peripheral neuropathy in both lower extremities
• Lower extremity pain for at least 6 months
• Visual analog scale score of ≥ 40 mm at Initial Screening (0 mm = no pain - 100 mm very severe pain)
• Symptoms from the Brief Pain Neuropathy Screening is ≤ 5 point difference between legs at Initial Screening
• The average daily pain intensity score of the Daily Pain and Sleep Interference Diary completed after medication wash-out is ≥ 4 with a standard deviation ≤ 2
• The physical examination component of the Michigan Neuropathy Screening Instrument Score is ≥ 3 at Screening
• Subjects on gabapentin (Neurontin), pregabalin (Lyrica), duloxetine (Cymbalta) for painful Diabetic Peripheral Neuropathy at study entry must be on stable regimen of these treatments for at least 3 months prior to study entry
• If female of childbearing potential, negative urine 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 that would prevent assessment of Diabetic Peripheral Neuropathy
• 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 disease, rheumatoid arthritis)
• Positive HIV or HTLV at Screening
• Active Hepatitis B or C as determined by Hepatitis B core antibody (HBcAb), antibody to Hepatitis B surface antigen (IgG and IgM; HBsAb), Hepatitis B surface antigen (HBsAg), and Hepatitis C antibodies (Anti HCV) at Screening
• Subjects with known immunosuppression or currently receiving immunosuppressive drugs, chemotherapy, or radiation therapy
• Stroke or myocardial infarction within last 3 months
• Specific laboratory values at Screening including: Hemoglobin 2.0 mg/dL; AST and/or ALT > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary
• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination
• Uncontrolled hypertension defined as sustained systolic blood pressure > 200 mmHg or diastolic BP > 110 mmHg at Screening
• Subjects with a recent history ( 81 mg daily of acetylsalicylic acid; subjects may be enrolled if willing/able to switch to ≤ 81 mg daily of acetylsalicylic acid or to another medication
• Subjects requiring regular COX-2 inhibitor drug(s) or non-specific COX-1/COX-2 inhibiting drugs, or high dose steroids (except inhaled steroids or ocular steroids) subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs until Day 180 of the study
• Major psychiatric disorder within the last 180 days that would interfere with study participation
• Body mass index > 45 kg/m2 at Screening
• Any lower extremity amputation due to diabetic complications
• Use of an investigational drug or treatment in past 6 months, or prior participation in any study of Engensis (VM202)
• Unable or unwilling to give informed consent