Painful Diabetic NeuropathiesPhase 2NCT01475786
Safety and Efficacy Study for the Treatment of Painful Diabetic Neuropathy
A Phase 2 study testing Low Dose: 16 mg Engensis (VM202) and High Dose: 32 mg Engensis (VM202) in people with Painful Diabetic Neuropathies, run by Helixmith Co., Ltd. at 17 sites in 2 countries.
Trial summary
The purpose of this study is to determine if Engensis (VM202) is safe and effective in treating painful diabetic neuropathy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Painful Diabetic Neuropathies
- What is being tested?
- Low Dose: 16 mg Engensis (VM202) and High Dose: 32 mg Engensis (VM202)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 17 sitesin 2 countries
- Study dates
- Aug 2012to Jun 2014
- Phase
- Phase 2
- 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 (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
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- 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
Who cannot join
- 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
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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 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
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States13 sites
The Neurosciences Institute Albany Medical College
Albany, New York, 12208
Beth Israel Deaconess
Boston, Massachusetts, 02115
Northwestern University
Chicago, Illinois, 60611
Houston Neurocare
Houston, Texas, 77030
The Methodist Hospital
Houston, Texas, 77030
Mount Sinai Medical Center
New York, New York, 10029
East Virginia Medical School Strelitz Diabetes Center
Norfolk, Virginia, 23510
University of Oklahoma Harold Hamm Diabetes Center
Oklahoma City, Oklahoma, 73104
Compass Research
Orlando, Florida, 32806
Palm Beach Neurological Center
Palm Beach Gardens, Florida, 33418
University of Utah
Salt Lake City, Utah, 84132
Rainier Clinical Research
Seattle, Washington, 98057
Diablo Clinical Research
Walnut Creek, California, 94598
South Korea4 sites
Sejong General Hospital
Bucheon-si, Sosa-gu, 422-711
Seoul National University Bundang Hospital
Seongnam, Bundang-gu, 463-707
Yonsei University College of Medicine Severance Hospital
Seoul, Seodaemun-gu, 120-752
The Catholic University of Korea Youido St. Mary's Hospital
Seoul, Yeongdeungpo-gu, 150-713
About this study
Official title: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Engensis (VM202) in Subjects With Painful Diabetic Peripheral Neuropathy
The purpose of this study is to determine if Engensis (VM202) is safe and effective in treating painful diabetic neuropathy.
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. 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
- Being tested
- Low Dose: 16 mg Engensis (VM202), High Dose: 32 mg Engensis (VM202), Control- Placebo (normal saline)
- Keywords
- nerve pain, diabetic nerve pain, throbbing, burning, painful feet, tingling, numbness, Engensis (VM202)
- Medical subject headings
- Diabetic Neuropathies, Neuralgia, Paresthesia, Hypesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low Dose: 16 mg Engensis (VM202)Biological
Also called Gene Therapy
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)
High Dose: 32 mg Engensis (VM202)Biological
Also called Gene Therapy
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)Other
Also called Normal saline
subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose 16mg Engensis (VM202) and Placebo | Active comparator | 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) Receives: Biological: Low Dose: 16 mg Engensis (VM202); Other: Control- Placebo (normal saline) |
| High Dose 32mg Engensis (VM202) | Active comparator | 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 Receives: Biological: High Dose: 32 mg Engensis (VM202) |
| Control - Placebo (normal saline) | Placebo comparator | 32 injections / calf of 0.5 mL normal saline at Day 0 and Day 14 Receives: Other: Control- Placebo (normal saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Study Endpoint Was the Change in Average 24-hour Pain Score From Baseline to the 6-month Follow-up.
The difference in the mean change of the 24 hour pain score was compared between the treatment groups and the placebo arm to determine treatment effect. The average pain scores were obtained from the Daily Pain and Sleep Interference Diary (recorded daily by subjects for 7 days during Screening prior to the first round of injections and again, before the 6 month follow-up). Subjects rated their 24-hor daily pain intensity according to the 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain).
Measured: seven (7) days before 9 Month visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2011 (estimated)
- Study startAug 2012
- Primary completion12 Mar 2014
- Study completionJun 2014
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 NeuropathiesStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helixmith Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jack Kessler, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01475786
- Sponsor's protocol ID
- VMDN-002
- Status last verified
- Aug 2025
- First submitted
- 15 Nov 2011
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26000320
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of Engensis (VM202) in Subjects With Painful Diabetic Peripheral Neuropathy
- ClinicalTrials.gov ID
- NCT01475786
- Acronym / sponsor ID
- VMDN-002
- Conditions
- Painful Diabetic Neuropathies
- Keywords
- nerve pain, diabetic nerve pain, throbbing, burning, painful feet, tingling, numbness, Engensis (VM202)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Helixmith Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Aug 2012
- Primary completion
- 12 Mar 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 21 Nov 2011 (estimated)
- Results
- Posted 3 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose 16mg Engensis (VM202) and Placebo | Active comparator | Biological: Low Dose: 16 mg Engensis (VM202), Other: Control- Placebo (normal saline)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) |
| High Dose 32mg Engensis (VM202) | Active comparator | Biological: High Dose: 32 mg 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 |
| Control - Placebo (normal saline) | Placebo comparator | Other: Control- Placebo (normal saline)32 injections / calf of 0.5 mL normal saline at Day 0 and Day 14 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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)
Key exclusion criteria (23 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low Dose: 16 mg Engensis (VM202)Also: Gene TherapySubjects 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) | Biological | Low Dose 16mg Engensis (VM202) and Placebo |
| High Dose: 32 mg Engensis (VM202)Also: Gene TherapySubjects 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) | Biological | High Dose 32mg Engensis (VM202) |
| Control- Placebo (normal saline)Also: Normal salinesubjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14. | Other | Control - Placebo (normal saline), Low Dose 16mg Engensis (VM202) and Placebo |
Primary outcome
The Primary Study Endpoint Was the Change in Average 24-hour Pain Score From Baseline to the 6-month Follow-up.
Time frame: seven (7) days before 9 Month visit
The difference in the mean change of the 24 hour pain score was compared between the treatment groups and the placebo arm to determine treatment effect. The average pain scores were obtained from the Daily Pain and Sleep Interference Diary (recorded daily by subjects for 7 days during Screening prior to the first round of injections and again, before the 6 month follow-up). Subjects rated their 24-hor daily pain intensity according to the 11-point numerical rating scale from 0 (no pain) to 10 (worst possible pain).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26000320Kessler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jack Kessler, MD principal investigator
Northwestern University
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Low Dose: 16 mg Engensis (VM202) and High Dose: 32 mg Engensis (VM202) in people with Painful Diabetic Neuropathies, run by Helixmith Co., Ltd. at 17 sites in 2 countries.
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 10 inclusion and 23 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 6 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 17 sites in United States, South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 3 Jul 2023). 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?
The Primary Study Endpoint Was the Change in Average 24-hour Pain Score From Baseline to the 6-month Follow-up. (time frame: seven (7) days before 9 Month visit). 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 NCT01475786, 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 6 Oct 2025.