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Efficacy and Safety of VM202 in Painful Diabetic Peripheral Neuropathy -The HOPES Trial

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ClinicalTrials.gov Identifier: NCT04087941
Recruitment Status : Not yet recruiting
First Posted : September 12, 2019
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
Christine N. Sang, MD, MPH, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE September 11, 2019
First Posted Date  ICMJE September 12, 2019
Last Update Posted Date September 16, 2019
Estimated Study Start Date  ICMJE November 2019
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
Change in 24-hour Morphine Milligram Equivalents (MME) [ Time Frame: baseline week to week prior to Day 180 ]
The percent change in 24-hour MME use from baseline week to the week prior to Day 180 obtained from the Daily Pain and Sleep Interference Diary
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2019)
  • Opioid use - mean dose [ Time Frame: Day 90, Day 180, Day 270, Day 365 ]
    mean dose of opioid reported in 24-hour MME at each timepoint
  • Opioid use - percent change from baseline [ Time Frame: Day 90, Day 180, Day 270, Day 365 ]
    percent change from baseline in 24-hour MME during the week prior to each timepoint
  • Opioid use - percent of subjects who are dose-reduced/opioid free [ Time Frame: Day 90, Day 180, Day 270, Day 365 ]
    percent of subjects whose daily opioid consumption is reduced by 50% and 100% (opioid-free) at each timepoint
  • Opioid-Related AE - Cognition [ Time Frame: Day 90, Day 180, Day 270, Day 365 ]
    Cognition as measured with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) assessed at each timepoint
  • Opioid-Related AE - Bowel Function [ Time Frame: Day 90, Day 180, Day 270, Day 365 ]
    Bowel Function Inventory-revised (BFI-R) assessed at each timepoint
  • Opioid-Related AE - Numerical Opioid Side Effect (NOSE) [ Time Frame: Day 90, Day 180, Day 270, Day 365 ]
    NOSE assessed at each timepoint
  • Efficacy- Change in Average Pain Intensity [ Time Frame: baseline week to week prior to Day 180 ]
    the change in average pain intensity from baseline week to the week prior to Day 180 obtained from the daily eDiaries
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of VM202 in Painful Diabetic Peripheral Neuropathy -The HOPES Trial
Official Title  ICMJE Hepatocyte Growth Factor for Opioid-Dependent Pain: Efficacy and Safety of VM202 in Painful Diabetic Peripheral Neuropathy (The HOPES Trial)
Brief Summary A double-blind, randomized, placebo-controlled, single-center, 12-month phase 2 study designed to assess the safety and efficacy of VM202 as a replacement for opioid analgesics in opioid-tolerant subjects with painful diabetic peripheral neuropathy (DPN).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
double-blind
Primary Purpose: Treatment
Condition  ICMJE Painful Diabetic Neuropathy
Intervention  ICMJE Biological: VM-202
VM202 is a DNA plasmid that contains novel genomic cDNA hybrid human hepatocyte growth factor (HGF) coding sequence (HGF-X7) expressing two isoforms of HGF, HGF 728 and HGF 723.
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Intervention: Biological: VM-202
  • Experimental: VM-202
    Intervention: Biological: VM-202
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥ 18 years to 75 years;
  2. 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;
  3. Taking 60 to 200 mg morphine milligram equivalents (MME)/day for painful DPN at study entry and must be on stable regimen starting at Day -21; percent of overall requirement as immediate release must be ≥ 30%;
  4. No significant changes anticipated in diabetes medication regimen;
  5. No new symptoms associated with diabetes within the last 3 months prior to study entry;
  6. Diagnosis of painful diabetic peripheral neuropathy in both lower extremities;
  7. Global pain intensity [Numerical rating scale, average NRS] score over the week prior to initial Screening visit must be ≥ 4 and ≤ 9 (0 = no pain - 10 = worst pain imaginable);
  8. Symptoms from the Brief Pain Neuropathy Screening (BPNS) is ≤ 5 point difference between legs at Initial Screening;
  9. The physical examination component of the Michigan Neuropathy Screening Instrument Score (MNSI) is ≥ 3 at Initial Screening;
  10. Subjects on gabapentin (Neurontin), pregabalin (Lyrica), or duloxetine (Cymbalta) for painful DPN at study entry must be on a stable regimen of these treatments for at least 7 days prior to start of oral placebo run-in; and
  11. If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study.

Exclusion Criteria:

  1. Small fiber polyneuropathy caused by condition other than diabetes;
  2. Additional pain syndrome of overall greater intensity than that of DPN that, in the opinion of the investigator, 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, in the opinion of the investigator;
  7. Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis), in the opinion of the investigator;
  8. Positive HIV or HTLV at Screening;
  9. Active Hepatitis B or C as determined by Hepatitis B core antibody (HBcAb; IgG and IgM), antibody to Hepatitis B surface antigen (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. Proliferative retinopathy within 5 years of signing consent or any ophthalmological condition which, in the opinion of the investigator, should be exclusionary; any condition that precludes 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 past Day -14:

    • skeletal muscle relaxants, benzodiazepines (except for stable bedtime dose),
    • capsaicin, local anesthetic creams and patches, isosorbide dinitrate (ISDN) spray,
    • transcutaneous electrical nerve stimulation (TENS), acupuncture
  17. If not using gabapentin (Neurontin), pregabalin (Lyrica), duloxetine (Cymbalta), any antidepressants (e.g., amitriptyline and venlafaxine), any other antiepileptics (e.g., valproic acid, carbamazepine, or vigabatrin), subjects must agree not to start these drugs until after Day 180. Subjects on these medications on day of informed consent must maintain a stable dose starting at Day -21 until Day 180; any changes in analgesic regimen after Day 180 are at the discretion of the investigator;
  18. Use of certain COX-1/COX-2 inhibitor drug(s), steroids (except inhaled, ocular, or intra-articular steroids), and anti-Vascular Endothelial Growth Factor (VEGF) agents; 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;
  19. Major psychiatric disorder within last 6 months that would interfere with study participation;
  20. Body mass index (BMI) > 45 kg/m2 at Screening;
  21. Any prior or lower extremity amputation due to diabetic complications;
  22. History of illicit drug or alcohol abuse / dependence in the past 2 years, including but not limited to, cocaine, amphetamines, non-prescribed opioids, and non-prescribed benzodiazepines);
  23. Use of an investigational drug or treatment in past 6 months; and
  24. Unable or unwilling to give informed consent.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christine N. Sang, MD, MPH 617-525-7246 csang@bwh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04087941
Other Study ID Numbers  ICMJE HOPES
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Christine N. Sang, MD, MPH, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christine N. Sang, MD, MPH Brigham and Women's Hospital
PRS Account Brigham and Women's Hospital
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP