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Painful Diabetic NeuropathyPhase 3NCT02427464

Phase 3 Gene Therapy for Painful Diabetic Neuropathy

A Phase 3 study testing Engensis (VM202) in people with Painful Diabetic Neuropathy and Diabetic Neuropathy, Painful, run by Helixmith Co., Ltd. at 25 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Engensis (VM202)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
507 participants
Where
25 sitesUnited States
Study dates
Apr 2016to Apr 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 29Show fewer
  • 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
  • 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
  • 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
  • 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
  • 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;
  • 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
  • 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
  • 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
  • Major psychiatric disorder within the last 180 days that would interfere with study participation
  • Body mass index > 45 kg/m2 at Screening
  • Any lower extremity amputation due to diabetic complications
  • Use of an investigational drug or treatment in past 6 months, or prior participation in any study of Engensis (VM202)
  • Unable or unwilling to give informed consent

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • The Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Northwestern University

    Chicago, Illinois, 60611

  • Innovative Research of West Florida

    Clearwater, Florida, 33756

  • Western Washington Medical Group

    Everett, Washington, 98208

  • Associated Neurologists of Southern Connecticut, PC

    Fairfield, Connecticut, 06824

  • University of Florida McKnight Brain Institute

    Gainesville, Florida, 32611

  • Nerve and Muscle Center of Texas

    Houston, Texas, 77030

  • UF Health College of Med, Jacksonville

    Jacksonville, Florida, 32207

  • University of Kansas Medical Center Research Institute

    Kansas City, Kansas, 66160

  • Clinical Trials, Inc.

    Little Rock, Arkansas, 72205

  • Richard S. Cherlin, MD

    Los Gatos, California, 95032

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center Department of Neurology

    New York, New York, 10032

  • EVMS (Eastern Virginia Medical School)

    Norfolk, Virginia, 23510

  • Compass Research, LLC

    Orlando, Florida, 32806

  • Arizona Research Center

    Phoenix, Arizona, 85023

  • Raleigh Neurology Associates, P.A.

    Raleigh, North Carolina, 27607

  • Rainier Clinical Research Center, Inc.

    Renton, Washington, 98057

  • Northern California Research

    Sacramento, California, 95821

  • University of Utah -Neurology

    Salt Lake City, Utah, 84132

  • Center for Clinical Research

    San Francisco, California, 94115

  • Neurological Research Institute

    Santa Monica, California, 90404

  • Clinical Research of West Florida

    Tampa, Florida, 33603

  • Diablo Clinical Research, Inc.

    Walnut Creek, California, 94598

  • Martin Foot and Ankle

    York, Pennsylvania, 17402

Other trials in United States

About this study

Official title: A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of VM202 in Participants With Painful Diabetic Peripheral Neuropathy

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.

Read the 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.

Being tested
Engensis (VM202), placebo
Keywords
diabetic, peripheral neuropathy, shooting pain, burning pain, pins and needles pain, foot pain, ViroMed
Medical subject headings
Diabetic Neuropathies, Peripheral Nervous System Diseases, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Engensis (VM202)Biological

    gene therapy

  • placeboOther

Study groups in NCT02427464
Study groupRoleWhat they receive
Engensis (VM202)ExperimentalSubjects 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
Receives: Biological: Engensis (VM202)
PlaceboPlacebo comparatorSubjects 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
Receives: Other: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 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.

  2. 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

    Measured: Baseline to Day 90

  3. Number of Participants With Treatment-emergent Adverse Events.

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

    Measured: Baseline to Day 270

Secondary outcomes (2)

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

    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 the Daily Pain and Sleep Interference Diary

    Measured: Baseline to Day 180

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

    The number of participants with at least a 50% 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

    Measured: Baseline to Day 180

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2015 (estimated)
  2. Study startApr 2016
  3. Primary completionApr 2019
  4. Study completionApr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
507 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02427464
Sponsor's protocol ID
VMDN-003
Status last verified
Aug 2025
First submitted
22 Apr 2015
Last updated
9 Oct 2025
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 33465273

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Engensis (VM202) in people with Painful Diabetic Neuropathy and Diabetic Neuropathy, Painful, run by Helixmith Co., Ltd. at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Average 24 Hour Pain Score From Baseline to Day 90 (time frame: 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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02427464, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.

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