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.
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
- Conditions the study is for
- Painful Diabetic Neuropathy, Diabetic Neuropathy, Painful
- 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
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
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- 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
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- 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
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
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
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)
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
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.
- First posted28 Apr 2015 (estimated)
- Study startApr 2016
- Primary completionApr 2019
- Study completionApr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Painful Diabetic NeuropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Helixmith Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- John A Kessler, MD, Principal investigator, Northwestern University
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
- Results posted
- Yes, on ClinicalTrials.gov
- 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