Safety and Efficacy Study for the Treatment of Painful Diabetic Neuropathy

NCT ID: NCT01475786

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2014-06-30

Brief Summary

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

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. 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.

Conditions

Painful Diabetic Neuropathies

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Low Dose 16mg Engensis (VM202) and Placebo

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)

Group Type: ACTIVE_COMPARATOR

Low Dose: 16 mg Engensis (VM202)

Intervention Type: BIOLOGICAL

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)

Control- Placebo (normal saline)

Intervention Type: OTHER

subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.

High Dose 32mg Engensis (VM202)

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

Group Type: ACTIVE_COMPARATOR

High Dose: 32 mg Engensis (VM202)

Intervention Type: BIOLOGICAL

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)

Control - Placebo (normal saline)

32 injections / calf of 0.5 mL normal saline at Day 0 and Day 14

Group Type: PLACEBO_COMPARATOR

Control- Placebo (normal saline)

Intervention Type: OTHER

subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.

Interventions

Low Dose: 16 mg Engensis (VM202)

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)

Intervention Type: BIOLOGICAL

High Dose: 32 mg Engensis (VM202)

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)

Intervention Type: BIOLOGICAL

Control- Placebo (normal saline)

subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.

Intervention Type: OTHER

Other Intervention Names

Gene Therapy; Gene Therapy; Normal saline

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Helixmith Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jack Kessler, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Diablo Clinical Research

Walnut Creek, California, United States

Compass Research

Orlando, Florida, United States

Palm Beach Neurological Center

Palm Beach Gardens, Florida, United States

Northwestern University

Chicago, Illinois, United States

Beth Israel Deaconess

Boston, Massachusetts, United States

The Neurosciences Institute Albany Medical College

Albany, New York, United States

Mount Sinai Medical Center

New York, New York, United States

University of Oklahoma Harold Hamm Diabetes Center

Oklahoma City, Oklahoma, United States

Houston Neurocare

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

East Virginia Medical School Strelitz Diabetes Center

Norfolk, Virginia, United States

Rainier Clinical Research

Seattle, Washington, United States

Seoul National University Bundang Hospital

Seongnam, Bundang-gu, South Korea

Yonsei University College of Medicine Severance Hospital

Seoul, Seodaemun-gu, South Korea

Sejong General Hospital

Bucheon-si, Sosa-gu, South Korea

The Catholic University of Korea Youido St. Mary's Hospital

Seoul, Yeongdeungpo-gu, South Korea

Countries

United States; South Korea

References

Kessler JA, Smith AG, Cha BS, Choi SH, Wymer J, Shaibani A, Ajroud-Driss S, Vinik A; VM202 DPN-II Study Group. Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy. Ann Clin Transl Neurol. 2015 May;2(5):465-78. doi: 10.1002/acn3.186. Epub 2015 Mar 5.

Reference Type: RESULT

PMID: 26000320 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VMDN-002

Identifier Type: -

Identifier Source: org_study_id