Clinical trial NCT01002235: Gene Therapy for Painful Diabetic Neuropathy
Official title: A Phase I/II, Open Label, Dose-Escalation Study to Assess the Safety and Tolerability of Engensis (VM202) in Patients With Painful Diabetic Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Painful Diabetic Peripheral Neuropathy
Keywords: Diabetic
Neuropathy
Peripheral
diabetes
Lead sponsor: Helixmith Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2009-10-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose Ranging
Primary purpose: TREATMENT

Brief summary: The purpose of this open label, Phase I/II, dose-escalation, 3-cohort, multicenter, 12-month study, is to assess the safety and tolerability of injecting Engensis (VM202) in the leg muscle in patients with painful diabetic peripheral neuropathy (DPN). The study will also assess the potential of VM202 to reduce the pain associated with diabetic peripheral neuropathy.

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 painful diabetic peripheral neuropathy (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.

The purpose of this open label, dose-escalation, 3-cohort study is to assess the safety and tolerability of injecting Engensis (VM202) in the leg muscle in patients with painful diabetic peripheral neuropathy. The study will also assess the potential of VM202 to reduce the pain associated with diabetic peripheral neuropathy.

Eligibility 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.

Primary outcomes:
measure: Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg
timeFrame: Day 0 to Day 365
Secondary outcomes:
measure: Percent Change From Baseline in Visual Analog Scale Pain Scores
timeFrame: Days 0, 90, 180, and 365
Other outcomes:
Locations:
city: Walnut Creek
country: United States
facility: Diablo Clinical Research Hospital
state: California
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern Memorial Hospital
name: John Kessler, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ajroud-Driss S, Christiansen M, Allen JA, Kessler JA. Phase 1/2 open-label dose-escalation study of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with painful diabetic peripheral neuropathy. Mol Ther. 2013 Jun;21(6):1279-86. doi: 10.1038/mt.2013.69. Epub 2013 Apr 23.