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Phase 3 Gene Therapy for Painful Diabetic Neuropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02427464
Recruitment Status : Completed
First Posted : April 28, 2015
Results First Posted : August 22, 2022
Last Update Posted : August 22, 2022
Sponsor:
Information provided by (Responsible Party):
Helixmith Co., Ltd.

Study Description
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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 IP treatment, whereas 7 participants did not receive IP 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.


Condition or disease Intervention/treatment Phase
Painful Diabetic Neuropathy Diabetic Neuropathy, Painful Biological: Engensis (VM202) Other: placebo Phase 3

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 (DPN) 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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 507 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : April 2016
Actual Primary Completion Date : April 2019
Actual Study Completion Date : April 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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
 Biological: Engensis (VM202)
gene therapy
Placebo Comparator: 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
 Other: placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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. ]
    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

  2. Participants With at Least at 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 90 [ Time Frame: 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

  3. Number of Participants With Treatment-emergent Adverse Events. [ Time Frame: Baseline to Day 270 ]
    Number of Participants with at least one treatment-emergent adverse events.


Secondary Outcome Measures :
  1. Change in the Average 24-hour Pain Score From Baseline to Day 180 [ Time Frame: 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

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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (VAS) score of ≥ 40 mm at Initial Screening (0 mm = no pain - 100 mm very severe pain)
  8. Symptoms from the Brief Pain Neuropathy Screening (BPNS) 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 (MNSI) is ≥ 3 at Screening
  11. Subjects on gabapentin (Neurontin), pregabalin (Lyrica), duloxetine (Cymbalta) for painful DPN 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 DPN
  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 (SBP) > 200 mmHg or diastolic BP (DBP) > 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 IM injection) and patches, isosorbide dinitrate (ISDN) 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 (BMI) > 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427464


Locations
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Sponsors and Collaborators
Helixmith Co., Ltd.
Investigators
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Principal Investigator: John A Kessler, MD Northwestern University
  Study Documents (Full-Text)

Documents provided by Helixmith Co., Ltd.:
Study Protocol  [PDF] September 5, 2019
Statistical Analysis Plan  [PDF] September 5, 2019

More Information
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Additional Information:

Publications of Results:

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Responsible Party: Helixmith Co., Ltd.
ClinicalTrials.gov Identifier: NCT02427464    
Other Study ID Numbers: VMDN-003
First Posted: April 28, 2015    Key Record Dates
Results First Posted: August 22, 2022
Last Update Posted: August 22, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Helixmith Co., Ltd.:
diabetic
peripheral neuropathy
shooting pain
burning pain
 pins and needles pain
foot pain
ViroMed
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Diabetic Neuropathies
Pain
Neuromuscular Diseases
Nervous System Diseases
 Neurologic Manifestations
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases