Phase 3 Gene Therapy for Painful Diabetic Neuropathy
Painful Diabetic Neuropathy, Diabetic Neuropathy, Painful
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
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
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
Experimental
Placebo Comparator
Engensis (VM202)
Placebo
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