Gene Therapy for Painful Diabetic Neuropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
ViroMed Co., Ltd. dba VM BioPharma
ClinicalTrials.gov Identifier:
NCT01002235
First received: October 24, 2009
Last updated: May 31, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to assess the safety and tolerability of injecting VM202 in the leg muscle in patients with painful diabetic neuropathy (DPN). The study will also assess the potential of VM202 to reduce the pain associated with DPN.


Condition Intervention Phase
Painful Diabetic Neuropathy
Genetic: VM202
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open Label, Dose-Escalation Study to Assess the Safety and Tolerability of VM202 in Patients 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:
  • Dose limiting toxicity [ Time Frame: Day 0 post-dose, Days 14, 21, 30, 60, 90, Month 6 and 12 ] [ Designated as safety issue: Yes ]
    Measurement of Adverse events and serum levels of HGF.


Secondary Outcome Measures:
  • Pain Levels [ Time Frame: Days 0, 14, 30, 60, 90, 180, 365 ] [ Designated as safety issue: No ]
    Change in pain level as measured by the VAS, SF-MPQ and BPI-DPN and the status of preexisting ulcers will also be reported.


Enrollment: 12
Study Start Date: February 2010
Study Completion Date: April 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Two divided doses of VM202 injected into the calf muscle on Day 0 and Day 14 for a total dose of 4 mg.
Genetic: VM202
Intramuscular injections in the calf on Day 0 and Day 14.
Experimental: Cohort 2
Two divided doses of VM202 injected into the calf muscle on Day 0 and Day 14 for a total dose of 8mg.
Genetic: VM202
Intramuscular injections in the calf on Day 0 and Day 14.
Experimental: Cohort 3
Two divided doses of VM202 injected into the calf muscle on Day 0 and Day 14 for a total dose of 16mg.
Genetic: VM202
Intramuscular injections in the calf on Day 0 and Day 14.

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.

Currently, there are no approved drugs or interventional strategies known to halt or reverse the progression of DPN. Treatments target pain reduction, physical function improvement, reduction of psychological distress, and quality of life improvements.

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%)
  • Diagnosis of painful diabetic peripheral neuropathy in both lower extremities
  • The physical examination component of the Michigan Neuropathy Screening Instrument Score (MNSI) is ≥ 3 at Screening
  • Visual analog scale (VAS) score of ≥ 4 cm at Screening (0 cm = no pain - 10 cm worst imaginable pain)
  • Stable treatment of diabetes for at least 3 months with no anticipated changes in medication regimen, and no new symptoms associated with diabetes
  • Lower extremity pain for at least 6 months
  • If female of childbearing potential, negative 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, Rheumatoid Arthritis)
  • Positive HIV or HTLV at Screening
  • Positive 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 or known immunosuppression or on chronic treatment with immunosuppressive drugs, chemotherapy or radiation therapy
  • Stroke or myocardial infarction within last 6 months;
  • Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination:

    • Cataract surgery within 6 months of trial;
    • Vascular lesions of the anterior segment of the eye (infection or ulceration of the cornea, rubeotic glaucoma, etc);
    • Vascular lesions of the posterior segment of the eye or proliferative retinopathy, macular edema, s/p photocoagulation for macular edema or proliferative retinopathy; sickle cell retinopathy, ischemic retinopathy due to retinal venous stasis or carotid artery disease;
    • Choroidal angiogenesis; and
    • Large elevated choroidal nevi, choroidal vascular tumors (choroidal hemangioma), or melanomas.
  • Specific laboratory values at Screening including: Hemoglobin < 9.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, Creatinine > 2.0 mg/dL; GFR < 50, AST and/or ALT > 2 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary;
  • Use of gamma-linolenic acid (GLA), alpha lipoic acid or any other high dose dietary antioxidant supplement for symptomatic relief of DPN;
  • Uncontrolled hypertension as defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at baseline/screening evaluation;
  • Patients with history 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);
  • Malignant tumors or abnormal screening test suspicious for cancer, or patients in whom screening exams indicate possible occult malignancy unless malignancy has been ruled out. Patients with family history of colon cancer in any first degree relative unless they have undergone a colonoscopy in the last 12 months with negative findings;
  • Elevated PSA unless prostate cancer has been excluded;
  • 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;
  • Major psychiatric disorder in past 6 months;
  • History of drug or alcohol abuse / dependence in the past 2 years;
  • History of recent tobacco abuse (within past 5 years);
  • BMI > 38 kg/m2;
  • Use of an investigational drug or treatment in past 12 months; and
  • 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: NCT01002235

Locations
United States, California
Diablo Clinical Research Hospital
Walnut Creek, California, United States, 94598
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States
Sponsors and Collaborators
ViroMed Co., Ltd. dba VM BioPharma
Investigators
Principal Investigator: John Kessler, M.D. Northwestern Memorial Hospital
  More Information

No publications provided

Responsible Party: ViroMed Co., Ltd. dba VM BioPharma
ClinicalTrials.gov Identifier: NCT01002235     History of Changes
Other Study ID Numbers: VMDN-001/D
Study First Received: October 24, 2009
Last Updated: May 31, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by ViroMed Co., Ltd. dba VM BioPharma:
Diabetic
Neuropathy
peripheral
diabetes

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

ClinicalTrials.gov processed this record on October 29, 2014