Safety and Efficacy Study for the Treatment of Painful Diabetic Neuropathy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ViroMed Co., Ltd. dba VM BioPharma
ClinicalTrials.gov Identifier:
NCT01475786
First received: November 15, 2011
Last updated: July 22, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to determine if VM202 is safe and effective in treating painful diabetic neuropathy.


Condition Intervention Phase
Painful Diabetic Neuropathies
Genetic: Low Dose: 16 mg VM202
Genetic: High Dose: 32 mg VM202
Genetic: Placebo (Normal Saline)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Assess the Safety and Efficacy of VM202 in Subjects With Painful Diabetic Peripheral Neuropathy

Resource links provided by NLM:


Further study details as provided by ViroMed Co., Ltd. dba VM BioPharma:

Primary Outcome Measures:
  • The primary study endpoint is the change in the average 24 hour pain score between baseline and the 6-month follow-up. [ Time Frame: seven (7) days before Day 0, Day 90, and the 6 Month and 9 Month visits ] [ Designated as safety issue: No ]
    The difference in the mean change of the 24 hour pain score will be compared between the treatment groups and the placebo arm to determine treatment effect. The average pain scores will be 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).


Secondary Outcome Measures:
  • Change in VAS score [ Time Frame: Screening, Day 0, Day 30, Day 60, Day 90, 6 months, and 9 months. ] [ Designated as safety issue: No ]
    The visual analog scale (VAS)scoring instrument is a 100-mm line, oriented horizontally, with the left end indicating "no pain" and the right end representing "very severe pain". The patient is asked to mark a place on the line corresponding to the current pain intensity. The distance along the scale is then converted into a numeric reading by measuring the distance of the patients mark in millimeters from the beginning of the scale (the 0 mark).

  • Change in mean Daily Pain and Sleep Interference Diary score from baseline to Day 90, 6 months and 9 months. [ Time Frame: Screening, Day 90, 6 months, 9 months. ] [ Designated as safety issue: No ]
    Subjects will be asked to keep a Daily Pain and Sleep Interference Diary. Subjects will be asked to rate their 24-hour average daily pain intensity score (0 = no pain, 10 = worst possible pain). The effect of pain on the subject's ability to sleep will be assessed using the sleep interference score.

  • Change in BPI-SF [ Time Frame: Day 0, Day 30, Day 60, Day 90, 6 months, and 9 months. ] [ Designated as safety issue: No ]
    The brief pain inventory (BPI-SF) will be self-administered during site visits on Day 0 before the treatment (injection), on Day 30, Day 60, Day 90, at 6 months and 9 months. The Questionnaire is a patient - completed numeric rating scale that assesses the severity of pain, its impact on daily functioning, and other aspects of pain (e.g. location of pain, relief from medications).

  • Patient's Global Impression of Change [ Time Frame: Day 30, Day 60, Day 90, 6 months, and 9 months. ] [ Designated as safety issue: No ]
    The patient's global impression of change after treatment will be measured using the Patient's Global Impression of Change (PGIC) questionnaire. This questionnaire measures a patient's perception of how treatment has affected their level of activity, symptoms, emotions, and overall quality of life.

  • Adverse events (including serious adverse events, and adverse events leading to treatment discontinuation) will be described according to severity and to their relationship with the study drug and injection procedure. [ Time Frame: Day 0, 14, 21, 30, 60, 90, Six and nine month ] [ Designated as safety issue: Yes ]
  • Change in symptoms of the Brief Peripheral Neuropathy Screening (BPNS) [ Time Frame: Screening and 6 months. ] [ Designated as safety issue: No ]
    Subject rates the severity of symptoms of peripheral neuropathy.

  • Change in MNSI score [ Time Frame: Screen, 6 months and 9 months ] [ Designated as safety issue: No ]
    The Michigan Neuropathy Screening Instrument (MNSI) will be conducted at Screening in order to confirm the diagnosis of diabetic peripheral neuropathy and at 6 months and 9 months to track disease progression.The MNSI is comprised of a subject questionnaire (15 questions) and of a physical evaluation which includes a foot inspection, vibration sensation testing, muscle stretch reflexes, and monofilament testing.


Other Outcome Measures:
  • Pharmacokinetics Determination of HGF serum levels [ Time Frame: Pre treatment Day 0, pre-treatment Day 14, Day 30, 60 and 90 ] [ Designated as safety issue: No ]
    Serum HGF will be determined by ELISA and analyzed by a central laboratory.

  • Pharmacokinetics -Number of copies of VM202 in whole blood [ Time Frame: Pre and post injection on Day 0 and Day 14, Day 21, 30, 60, and 90 ] [ Designated as safety issue: No ]
    The number of copies of VM202 in whole blood will be determined by PCR. Results will be analyzed by a central laboratory


Estimated Enrollment: 100
Study Start Date: August 2012
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low Dose VM202
DNA plasmid and Normal Saline
Genetic: Low Dose: 16 mg VM202

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)
  • 16 injections of 0.5mL of normal saline / calf

Day 14 - 32 injections / calf:

  • 16 injections of 0.5mL of VM202 / calf - (4 mg of VM202 / calf)
  • 16 injections of 0.5mL of normal saline / calf
Other Name: Gene Therapy
Active Comparator: High Dose VM202
DNA Plasmid
Genetic: High Dose: 32 mg VM202

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)
Other Name: Gene Therapy
Placebo Comparator: Control - Placebo (normal saline)
Normal Saline
Genetic: Placebo (Normal Saline)
subjects will receive thirty-two (32) 0.5 mL injections of normal saline on Day 0 and Day 14.
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01475786

Locations
United States, California
Diablo Clinical Research
Walnut Creek, California, United States, 94598
United States, Florida
Compass Research
Orlando, Florida, United States, 32806
Palm Beach Neurological Center
Palm Beach Gardens, Florida, United States, 33418
United States, Illinois
Northwestern University
Chicago, Illinois, United States
United States, Massachusetts
Beth Israel Deaconess
Boston, Massachusetts, United States, 02115
United States, New York
The Neurosciences Institute Albany Medical College
Albany, New York, United States, 12208
Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Oklahoma
University of Oklahoma Harold Hamm Diabetes Center
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
The Methodist Hospital
Houston, Texas, United States, 77030
Houston Neurocare
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
East Virginia Medical School Strelitz Diabetes Center
Norfolk, Virginia, United States, 23510
United States, Washington
Rainier Clinical Research
Seattle, Washington, United States, 98057
Korea, Republic of
Seoul National University Bundang Hospital
Seongnam, Bundang-gu, Korea, Republic of, 463-707
Yonsei University College of Medicine Severance Hospital
Seoul, Seodaemun-gu, Korea, Republic of, 120-752
Sejong General Hospital
Bucheon, Sosa-gu, Korea, Republic of, 422-711
The Catholic University of Korea Youido St. Mary's Hospital
Seoul, Yeongdeungpo-gu, Korea, Republic of, 150-713
Sponsors and Collaborators
ViroMed Co., Ltd. dba VM BioPharma
Investigators
Principal Investigator: Jack Kessler, MD Northwestern University
  More Information

Additional Information:
No publications provided

Responsible Party: ViroMed Co., Ltd. dba VM BioPharma
ClinicalTrials.gov Identifier: NCT01475786     History of Changes
Other Study ID Numbers: VMDN-002
Study First Received: November 15, 2011
Last Updated: July 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by ViroMed Co., Ltd. dba VM BioPharma:
nerve pain
diabetic nerve pain
throbbing
burning
painful feet
tingling
numbness

Additional relevant MeSH terms:
Diabetic Neuropathies
Pain
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on August 28, 2014