Safety and Efficacy Study for the Treatment of Painful Diabetic Neuropathy

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

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

Official Title
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A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Engensis (VM202) in Subjects With Painful Diabetic Peripheral Neuropathy

Conditions
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Painful Diabetic Neuropathies

Intervention / Treatment
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* Biological: Low Dose: 16 mg Engensis (VM202)
* Biological: High Dose: 32 mg Engensis (VM202)
* Other: Control- Placebo (normal saline)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low Dose 16mg Engensis (VM202) and Placebo<br>intramuscular injections in each calf for a total of 16mg Engensis (VM202): Day 0 - 32 injections / calf 16 injections of 0.5mL of VM202 / calf - (4 mg of VM202 / calf) and 16 injections of normal saline 0.5mL / calf Day 14 - 32 injections / calf and 16 injections of normal saline 0.5mL / calf 16 injections of 0.5mL of VM202 / calf - (4 mg of VM202 / calf) | Biological: Low Dose: 16 mg Engensis (VM202)<br>* 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)<br>* Other names: Gene Therapy;Other: Control- Placebo (normal saline)<br>* subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.<br>* Other names: Normal saline;|
| Active Comparator: High Dose 32mg Engensis (VM202)<br>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) For a total of 32mg VM202 | Biological: High Dose: 32 mg Engensis (VM202)<br>* 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)<br>* Other names: Gene Therapy;|
| Placebo Comparator: Control - Placebo (normal saline)<br>32 injections / calf of 0.5 mL normal saline at Day 0 and Day 14 | Other: Control- Placebo (normal saline)<br>* subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Study Endpoint Was the Change in Average 24-hour Pain Score From Baseline to the 6-month Follow-up. | The difference in the mean change of the 24 hour pain score was compared between the treatment groups and the placebo arm to determine treatment effect. The average pain scores were obtained from the Daily Pain and Sleep Interference Diary (recorded daily by subjects for 7 days during Screening prior to the first round of injections and again, before the 6 month follow-up). Subjects rated their 24-hor daily pain intensity according to the 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain). | seven (7) days before Day 0, Day 90, and the 6 Month and 9 Month visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nerve pain, diabetic nerve pain, throbbing, burning, painful feet, tingling, numbness, Engensis (VM202)