Phase 3 Gene Therapy for Painful Diabetic Neuropathy

NCT ID: NCT02427464

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 507 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2019-04-30

Brief Summary

The purpose of this study is to determine the safety and efficacy of bilateral intramuscular injections of VM202 versus placebo in the treatment of painful diabetic peripheral neuropathy.

A total of 507 of 477 planned participants were randomized in a 2:1 ratio to one of two treatment groups. Note that 500 participants received Investigational product treatment, whereas 7 participants did not receive Investigational product treatment.

Treatments - Engensis (VM202) - 336 Engensis of 318 planned participants

Control - Placebo (VM202 vehicle) - 164 Placebo of 159 planned participants

Randomization were stratified by current use of gabapentin and/or pregabalin.

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. Current treatments of diabetic peripheral neuropathy are based on either pathogenetic mechanisms or symptomatic relief. A number of clinical trials have established symptomatic treatment but for pathogenetic mechanisms, the only proven treatment strategy is strict glycemic control. 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 Neuropathy; Diabetic Neuropathy, Painful

Study Design

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

Study Groups

Engensis (VM202)

Subjects randomized to the Engensis (VM202) treatment arm received the following intramuscular injections in each calf:

• Day 0 - 16 injections of 0.5mL of VM202 / calf
• Day 14 - 16 injections of 0.5mL of VM202 / calf
• Day 90 - 16 injections of 0.5mL of VM202 / calf
• Day 104 - 16 injections of 0.5mL of VM202 / calf

Group Type: EXPERIMENTAL

Engensis (VM202)

Intervention Type: BIOLOGICAL

gene therapy

Placebo

Subjects in the placebo control group received the following intramuscular injections in each calf:

• Day 0 - 16 injections of 0.5mL of VM202 vehicle / calf
• Day 14 - 16 injections of 0.5mL of VM202 vehicle / calf
• Day 90 - 16 injections of 0.5mL of VM202 vehicle / calf
• Day 104 - 16 injections of 0.5mL of VM202 vehicle / calf

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Interventions

Engensis (VM202)

gene therapy

Intervention Type: BIOLOGICAL

placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years to ≤ 75 years

2. 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)

3. No significant changes anticipated in diabetes medication regimen

4. No new symptoms associated with diabetes within the last 3 months prior to study entry

5. Diagnosis of painful diabetic peripheral neuropathy in both lower extremities

6. Lower extremity pain for at least 6 months

7. Visual analog scale score of ≥ 40 mm at Initial Screening (0 mm = no pain - 100 mm very severe pain)

8. Symptoms from the Brief Pain Neuropathy Screening is ≤ 5 point difference between legs at Initial Screening

9. 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

10. The physical examination component of the Michigan Neuropathy Screening Instrument Score is ≥ 3 at Screening

11. 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

12. If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study

Exclusion Criteria

1. Peripheral neuropathy caused by condition other than diabetes

2. Other pain more severe than neuropathic pain that would prevent assessment of Diabetic Peripheral Neuropathy

3. Progressive or degenerative neurological disorder

4. Myopathy

5. Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease)

6. Active infection

7. Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)

8. Positive HIV or HTLV at Screening

9. 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

10. Subjects with known immunosuppression or currently receiving immunosuppressive drugs, chemotherapy, or radiation therapy

11. Stroke or myocardial infarction within last 3 months

12. 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

13. Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination

14. Uncontrolled hypertension defined as sustained systolic blood pressure > 200 mmHg or diastolic BP > 110 mmHg at Screening

15. Subjects 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 for one year); subjects 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

16. Use of the following drugs / therapeutics is prohibited. Subjects may participate in the study if they are willing to discontinue use of these drugs / therapeutics 7 days prior to starting the 7 Day Daily Pain and Sleep Interference Diary. Subjects must refrain from taking these drugs or undergoing these therapies for the duration of the study

• skeletal muscle relaxants, opioids, benzodiazepines (except for stable bedtime dose),
• capsaicin, local anesthetic creams (except for lidocaine cream prior to intramuscular injection) and patches, isosorbide dinitrate spray,
• transcutaneous electrical nerve stimulation (TENS), acupuncture

17. If not using gabapentin (Neurontin) or pregabalin (Lyrica), subjects must agree not to start these drugs for the first 180 days of the study. Subjects on these medications at study entry must maintain a stable dose until Day 180 of the study;

18. If not using duloxetine (Cymbalta), any antidepressants (e.g., amitriptyline and venlafaxine), any other antiepileptics (e.g., valproic acid, carbamazepine, vigabatrin), subjects must agree not to start these drugs for the first 6 months of the study.

Subjects on these medications at study entry must maintain a stable dose until Day 180 of the study

19. Subjects requiring > 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

20. 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

21. Major psychiatric disorder within the last 180 days that would interfere with study participation

22. Body mass index > 45 kg/m2 at Screening

23. Any lower extremity amputation due to diabetic complications

24. Use of an investigational drug or treatment in past 6 months, or prior participation in any study of Engensis (VM202)

25. 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

John A Kessler, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Arizona Research Center

Phoenix, Arizona, United States

Clinical Trials, Inc.

Little Rock, Arkansas, United States

Richard S. Cherlin, MD

Los Gatos, California, United States

Northern California Research

Sacramento, California, United States

Center for Clinical Research

San Francisco, California, United States

Neurological Research Institute

Santa Monica, California, United States

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Associated Neurologists of Southern Connecticut, PC

Fairfield, Connecticut, United States

Innovative Research of West Florida

Clearwater, Florida, United States

University of Florida McKnight Brain Institute

Gainesville, Florida, United States

UF Health College of Med, Jacksonville

Jacksonville, Florida, United States

Compass Research, LLC

Orlando, Florida, United States

Clinical Research of West Florida

Tampa, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Kansas Medical Center Research Institute

Kansas City, Kansas, United States

The Brigham and Women's Hospital

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Columbia University Medical Center Department of Neurology

New York, New York, United States

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, United States

Martin Foot and Ankle

York, Pennsylvania, United States

Nerve and Muscle Center of Texas

Houston, Texas, United States

University of Utah -Neurology

Salt Lake City, Utah, United States

EVMS (Eastern Virginia Medical School)

Norfolk, Virginia, United States

Western Washington Medical Group

Everett, Washington, United States

Rainier Clinical Research Center, Inc.

Renton, Washington, United States

Countries

United States

References

Kessler JA, Shaibani A, Sang CN, Christiansen M, Kudrow D, Vinik A, Shin N; VM202 study group. Gene therapy for diabetic peripheral neuropathy: A randomized, placebo-controlled phase III study of VM202, a plasmid DNA encoding human hepatocyte growth factor. Clin Transl Sci. 2021 May;14(3):1176-1184. doi: 10.1111/cts.12977. Epub 2021 Feb 2.

Reference Type: RESULT

PMID: 33465273 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VMDN-003

Identifier Type: -

Identifier Source: org_study_id