search
Back to results

Phase 3 Gene Therapy for Painful Diabetic Neuropathy

Primary Purpose

Painful Diabetic Neuropathy, Diabetic Neuropathy, Painful

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Engensis (VM202)
placebo
Sponsored by
Helixmith Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Painful Diabetic Neuropathy focused on measuring diabetic, peripheral neuropathy, shooting pain, burning pain, pins and needles pain, foot pain, ViroMed

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arizona Research Center
  • Clinical Trials, Inc.
  • Richard S. Cherlin, MD
  • Northern California Research
  • Center for Clinical Research
  • Neurological Research Institute
  • Diablo Clinical Research, Inc.
  • Associated Neurologists of Southern Connecticut, PC
  • Innovative Research of West Florida
  • University of Florida McKnight Brain Institute
  • UF Health College of Med, Jacksonville
  • Compass Research, LLC
  • Clinical Research of West Florida
  • Northwestern University
  • University of Kansas Medical Center Research Institute
  • The Brigham and Women's Hospital
  • University of Minnesota
  • Columbia University Medical Center Department of Neurology
  • Raleigh Neurology Associates, P.A.
  • Martin Foot and Ankle
  • Nerve and Muscle Center of Texas
  • University of Utah -Neurology
  • EVMS (Eastern Virginia Medical School)
  • Western Washington Medical Group
  • Rainier Clinical Research Center, Inc.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Engensis (VM202)

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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
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
Number of Participants With Treatment-emergent Adverse Events.
Number of Participants with at least one treatment-emergent adverse events.

Secondary Outcome Measures

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
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

Full Information

First Posted
April 22, 2015
Last Updated
July 26, 2022
Sponsor
Helixmith Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT02427464
Brief Title
Phase 3 Gene Therapy for Painful Diabetic Neuropathy
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 Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
April 2019 (Actual)
Study Completion Date
April 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Helixmith Co., Ltd.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Painful Diabetic Neuropathy, Diabetic Neuropathy, Painful
Keywords
diabetic, peripheral neuropathy, shooting pain, burning pain, pins and needles pain, foot pain, ViroMed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
507 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Engensis (VM202)
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Engensis (VM202)
Intervention Description
gene therapy
Intervention Type
Other
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
Change in the Average 24 Hour Pain Score From Baseline to Day 90
Description
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
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.
Title
Participants With at Least at 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 90
Description
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
Time Frame
Baseline to Day 90
Title
Number of Participants With Treatment-emergent Adverse Events.
Description
Number of Participants with at least one treatment-emergent adverse events.
Time Frame
Baseline to Day 270
Secondary Outcome Measure Information:
Title
Change in the Average 24-hour Pain Score From Baseline to Day 180
Description
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
Time Frame
Baseline to Day 180
Title
Participants With at Least a 50 Percent Reduction in Average 24-hour Pain Score From Baseline to Day 180
Description
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
Time Frame
Baseline to Day 180

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 (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 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 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 If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study Exclusion Criteria: Peripheral neuropathy caused by condition other than diabetes Other pain more severe than neuropathic pain that would prevent assessment of DPN 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 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 (SBP) > 200 mmHg or diastolic BP (DBP) > 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 IM injection) and patches, isosorbide dinitrate (ISDN) 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 (BMI) > 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John A Kessler, MD
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arizona Research Center
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
Clinical Trials, Inc.
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Richard S. Cherlin, MD
City
Los Gatos
State/Province
California
ZIP/Postal Code
95032
Country
United States
Facility Name
Northern California Research
City
Sacramento
State/Province
California
ZIP/Postal Code
95821
Country
United States
Facility Name
Center for Clinical Research
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Neurological Research Institute
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Diablo Clinical Research, Inc.
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
Associated Neurologists of Southern Connecticut, PC
City
Fairfield
State/Province
Connecticut
ZIP/Postal Code
06824
Country
United States
Facility Name
Innovative Research of West Florida
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
University of Florida McKnight Brain Institute
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
UF Health College of Med, Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
Compass Research, LLC
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Clinical Research of West Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33603
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Kansas Medical Center Research Institute
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
The Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Columbia University Medical Center Department of Neurology
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Raleigh Neurology Associates, P.A.
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Martin Foot and Ankle
City
York
State/Province
Pennsylvania
ZIP/Postal Code
17402
Country
United States
Facility Name
Nerve and Muscle Center of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah -Neurology
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
EVMS (Eastern Virginia Medical School)
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
Western Washington Medical Group
City
Everett
State/Province
Washington
ZIP/Postal Code
98208
Country
United States
Facility Name
Rainier Clinical Research Center, Inc.
City
Renton
State/Province
Washington
ZIP/Postal Code
98057
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33465273
Citation
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.
Results Reference
result
Links:
URL
https://www.cts-journal.com
Description
Clin Transl Sci. 2021;00:1-9

Learn more about this trial

Phase 3 Gene Therapy for Painful Diabetic Neuropathy

We'll reach out to this number within 24 hrs