Phase 3 Gene Therapy for Painful Diabetic Neuropathy

NCT02427464 | Completed Phase 3 Results DMC

• 1 other identifier: VMDN-003
• Study Type: interventional
• Target: 507
• Locations: 1 country
• Sites: 25

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.

Conditions

Painful Diabetic Neuropathy; Diabetic Neuropathy, Painful

Keywords

diabetic; peripheral neuropathy; shooting pain; burning pain; pins and needles pain; foot pain; ViroMed

Outcome Measures

Primary Outcomes (3)

• Change in the Average 24 Hour Pain Score From Baseline to Day 90

  Participants rated their 24-hour average daily pain intensity score using an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain) in a Daily Pain and Sleep Interference Diary

  The Pain and Sleep Interference diary was completed by participants for at least 5 assessments during a 7-day period at Screening (the mean 24-hour score was the reference/baseline score) and within 14 days prior to Day 90 visit.

• Participants With at Least at 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 90

  Number of participants with at least a 50 percent reduction in average 24-hour pain score, using an 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain) in the Daily Pain and Sleep Interference Diary

  Baseline to Day 90

• Number of Participants With Treatment-emergent Adverse Events.

  Number of Participants with at least one treatment-emergent adverse events.

  Baseline to Day 270

Secondary Outcomes (2)

• Change in the Average 24-hour Pain Score From Baseline to Day 180

  Baseline to Day 180

• Participants With at Least a 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 180

  Baseline to Day 180

Study Arms (2)

Engensis (VM202)

EXPERIMENTAL

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

Biological: Engensis (VM202)

Placebo

PLACEBO COMPARATOR

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

Other: placebo

Interventions

Engensis (VM202) BIOLOGICAL

gene therapy

Engensis (VM202)

placebo OTHER

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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 (\< 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
• 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

Sponsors & Collaborators

• Helixmith Co., Ltd.: lead

Study Sites (25)

Arizona Research Center

Phoenix, Arizona, 85023, United States

Location

Clinical Trials, Inc.

Little Rock, Arkansas, 72205, United States

Location

Richard S. Cherlin, MD

Los Gatos, California, 95032, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Center for Clinical Research

San Francisco, California, 94115, United States

Location

Neurological Research Institute

Santa Monica, California, 90404, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

Associated Neurologists of Southern Connecticut, PC

Fairfield, Connecticut, 06824, United States

Location

Innovative Research of West Florida

Clearwater, Florida, 33756, United States

Location

University of Florida McKnight Brain Institute

Gainesville, Florida, 32611, United States

Location

UF Health College of Med, Jacksonville

Jacksonville, Florida, 32207, United States

Location

Compass Research, LLC

Orlando, Florida, 32806, United States

Location

Clinical Research of West Florida

Tampa, Florida, 33603, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

The Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Columbia University Medical Center Department of Neurology

New York, New York, 10032, United States

Location

Raleigh Neurology Associates, P.A.

Raleigh, North Carolina, 27607, United States

Location

Martin Foot and Ankle

York, Pennsylvania, 17402, United States

Location

Nerve and Muscle Center of Texas

Houston, Texas, 77030, United States

Location

University of Utah -Neurology

Salt Lake City, Utah, 84132, United States

Location

EVMS (Eastern Virginia Medical School)

Norfolk, Virginia, 23510, United States

Location

Western Washington Medical Group

Everett, Washington, 98208, United States

Location

Rainier Clinical Research Center, Inc.

Renton, Washington, 98057, United States

Location

Related Publications (1)

• 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.

  PMID: 33465273 RESULT

MeSH Terms

Conditions

Diabetic Neuropathies; Peripheral Nervous System Diseases; Pain

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jinsub Lee, PhD
• Organization: Helixmith Co., Ltd.

jinsub.lee@helixmith.com

+82-10-8256-0439

Study Officials

• John A Kessler, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: April 28, 2015
• Study Start: April 1, 2016
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: October 9, 2025
• Results First Posted: August 22, 2022

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)