Safety and Efficacy Study for the Treatment of Painful Diabetic Neuropathy
Condition: Painful Diabetic Neuropathies
MeSH terms: Diabetic Neuropathies; Pain
Intervention: Low Dose: 16 mg Engensis (VM202); High Dose: 32 mg Engensis (VM202); Control- Placebo (normal saline)
Intervention description: Subjects in the Low Dose Group (8mg VM202 / leg) will receive the following intramuscular injections in each calf:
Day 0 - 32 injections / calf:
• 16 injections of 0.5mL of VM202 / calf - (4 mg of VM202 / calf)
Day 14 - 32 injections / calf:
• 16 injections of 0.5mL of VM202 / calf - (4 mg of VM202 / calf); Subjects in the High Dose Group (16 mg VM202 / leg) will receive the following intramuscular injections in each calf:
Day 0
• 32 injections of 0.5mL of VM202 / calf (8 mg of VM202 / calf)
Day 14
• 32 injections of 0.5mL of VM202 / calf (8 mg of VM202 / calf); subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: nerve pain; diabetic nerve pain; throbbing; burning; painful feet; tingling; numbness; Engensis (VM202)

Summary:

      The purpose of this study is to determine if Engensis (VM202) is safe and effective in
      treating painful diabetic neuropathy.
    

Eligibility criteria:

        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% at Screening) and currently on oral medication
             and/or insulin

          -  Diagnosis of painful diabetic peripheral neuropathy in both lower extremities

          -  Lower extremity pain for at least 6 months

          -  Visual analog scale (VAS) score of ≥ 40 mm at Initial Screening (0 mm = no pain - 100
             mm very severe pain)

          -  Symptoms from the Brief Pain Neuropathy Screening (BPNS) 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 (MNSI) is ≥ 3 at Screening

          -  Stable treatment of diabetes for at least 3 months with no anticipated changes in
             medication regimen, and no new symptoms associated with diabetes

          -  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

          -  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 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

          -  Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that
             preclude standard ophthalmologic examination

          -  Specific laboratory values at Screening including: Hemoglobin < 8.0 g/dL, WBC < 3,000
             cells per microliter, platelet count <75,000/mm3, Creatinine > 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

          -  Uncontrolled hypertension as defined as sustained systolic blood pressure (SBP) > 200
             mmHg or diastolic BP (DBP) > 110 mmHg at Screening

          -  Patients with a recent history (< 5 years) 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); patients with family history of colon cancer
             in any first degree relative are excluded unless they have undergone a colonoscopy in
             the last 12 months with negative findings

          -  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

          -  Use of any opioids; subjects may be enrolled if willing and able to discontinue use of
             these drugs 14 days prior to starting the 7 Day Daily Pain and Sleep Interference
             Diary and refrain from taking these drugs for the duration of the study

          -  Subjects requiring regular COX-2 inhibitor drug(s) or non-specific COX-1/COX-2
             inhibiting drugs, or high dose steroids (excepting inhaled 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 for the duration of the study;

          -  Major psychiatric disorder in within last 6 months

          -  Body mass index (BMI) > 45 kg/m2 at Screening

          -  Any lower extremity amputation

          -  Use of an investigational drug or treatment in past 6 months

          -  Unable or unwilling to give informed consent