Painful Diabetic Peripheral Neuropathy
Conditions
Keywords
Diabetic, Neuropathy, Peripheral, diabetes
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.
Interventions
BIOLOGICALVM202
Intramuscular injections in the calf on Day 0 and Day 14.
Sponsors
Helixmith Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose Ranging
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Day 0 to Day 365 | Treatment-emergent adverse events are any adverse events that occurred after the first dose of Engensis (VM202). This is a dose escalation study. Cohorts of increasing dose will be enrolled sequentially. Dose escalation decisions (permission to treat at higher doses) will be made by the Data Safety Monitoring Board based on review of adverse events and on the occurrence of dose limiting toxicities in each cohort. The decision to proceed to the next higher dose cohort will be made according to the scheme described in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Visual Analog Scale Pain Scores | Days 0, 90, 180, and 365 | Percent change in median Visual Analog Scale Pain Scores from baseline (Day 0). The Visual Analog Scale Pain scoring instrument is a 10-cm line, oriented horizontally, with the left end (0 cm, is 0 Percent) indicating no pain and the right end (10 cm, is 100 percent) representing pain as bad as it can be. The Change from Baseline of the Visual Analog Scale Pain Score is the difference between the Day 0 and the Days 90, 180 and 365 scores. A negative difference in the Change from Baseline of the Visual Analog Scale Pain Scores, indicates an improvement (reduction of pain severity) of the treated groups Visual Analog Score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Engensis 4 mg Subjects received Intramuscular injections of Engensis to the calf on Days 0 and 14 | 4 |
| Engensis 8 mg Subjects received Intramuscular injections to the calf on Days 0 and 14 | 4 |
| Engensis 16 mg Subjects received Intramuscular injections of Engensis on Days 0 and 14 | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Engensis 4 mg | Engensis 8 mg | Engensis 16 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 7 | 61.3 years STANDARD_DEVIATION 7.1 | 54.8 years STANDARD_DEVIATION 12.4 | 58.8 years STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 3 / 4 | 2 / 4 | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg
Treatment-emergent adverse events are any adverse events that occurred after the first dose of Engensis (VM202). This is a dose escalation study. Cohorts of increasing dose will be enrolled sequentially. Dose escalation decisions (permission to treat at higher doses) will be made by the Data Safety Monitoring Board based on review of adverse events and on the occurrence of dose limiting toxicities in each cohort. The decision to proceed to the next higher dose cohort will be made according to the scheme described in the protocol.
Time frame: Day 0 to Day 365
Population: The Safety Population included all participants who received at least one dose of Engensis (VM202) from Day 0 to Day 365
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Viral infection | 0 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Diarrhoea | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Subjects with any TEAEs | 3 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Sinusitis | 0 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dry mouth | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Benign prostatic hyperplasia | 0 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dyspepsia | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Musculoskeletal pain | 0 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Ingrowing nail | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Foot fracture | 0 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dry eye | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Back pain | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Injection site reaction | 1 Participants |
| Engensis 4 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Retinal vascular disorder | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Injection site reaction | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Subjects with any TEAEs | 2 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Back pain | 1 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Musculoskeletal pain | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dry eye | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Diarrhoea | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dry mouth | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dyspepsia | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Sinusitis | 1 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Viral infection | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Retinal vascular disorder | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Foot fracture | 0 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Benign prostatic hyperplasia | 1 Participants |
| Engensis 8 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Ingrowing nail | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Ingrowing nail | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Viral infection | 1 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dry eye | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Benign prostatic hyperplasia | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Injection site reaction | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Musculoskeletal pain | 1 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Subjects with any TEAEs | 2 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dry mouth | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Foot fracture | 1 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Dyspepsia | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Diarrhoea | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Back pain | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Sinusitis | 0 Participants |
| Engensis 16 mg | Treatment-emergent Adverse Events for Participants Who Received Engensis 4 mg, 8 mg, or 16 mg | Retinal vascular disorder | 1 Participants |
Secondary
Percent Change From Baseline in Visual Analog Scale Pain Scores
Percent change in median Visual Analog Scale Pain Scores from baseline (Day 0). The Visual Analog Scale Pain scoring instrument is a 10-cm line, oriented horizontally, with the left end (0 cm, is 0 Percent) indicating no pain and the right end (10 cm, is 100 percent) representing pain as bad as it can be. The Change from Baseline of the Visual Analog Scale Pain Score is the difference between the Day 0 and the Days 90, 180 and 365 scores. A negative difference in the Change from Baseline of the Visual Analog Scale Pain Scores, indicates an improvement (reduction of pain severity) of the treated groups Visual Analog Score.
Time frame: Days 0, 90, 180, and 365
Population: Change from Baseline (Day 0) to visits Day 90, Day 180, and Day 365, in the Intent-to-treat (ITT) population participants who received all assigned doses of Engensis and had evaluable data at a follow-up visit
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Engensis 4 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 180 | -26.16 percentage of Change from Baseline | Standard Deviation 84.35 |
| Engensis 4 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 90 | -19.19 percentage of Change from Baseline | Standard Deviation 71.53 |
| Engensis 4 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 365 | -42.27 percentage of Change from Baseline | Standard Deviation 108.26 |
| Engensis 8 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 180 | -58.40 percentage of Change from Baseline | Standard Deviation 39.36 |
| Engensis 8 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 90 | -40.76 percentage of Change from Baseline | Standard Deviation 28.55 |
| Engensis 8 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 365 | -67.57 percentage of Change from Baseline | Standard Deviation 47.56 |
| Engensis 16 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 90 | -40.15 percentage of Change from Baseline | Standard Deviation 21.5 |
| Engensis 16 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 365 | -46.97 percentage of Change from Baseline | Standard Deviation 29.01 |
| Engensis 16 mg | Percent Change From Baseline in Visual Analog Scale Pain Scores | Day 180 | -57.07 percentage of Change from Baseline | Standard Deviation 30.26 |