Study to Assess Safety and Efficacy of Engensis in Painful Diabetic Peripheral Neuropathy

Ki vehet részt

• Male or female participants age ≥ 18 years at time of completion of the informed consent process
• Type 1 or 2 diabetes mellitus and on current Standards of Medical Care in Diabetes - 2020 optimal guideline-directed medical therapy in participants (including vaccine recommendations if possible), and without unstable diabetes or significant medical problems, such as progressive end-organ disease, within 3 months of or during Screening, in the judgment of the Investigator
• Glycosylated HbA1c of ≤ 10.0% using the first assessment collected during Screening
• Documented diagnosis of bilateral painful diabetic peripheral neuropathy in both lower extremities at least 6 months prior to Screening
• An Average Daily Pain Score ≥ 4 (standard deviation ≥ 0.3 and ≤ 1.5) that was completed during the 7 days prior to randomization (Day 0)
• The physical examination component of the Michigan Neuropathy Screening Instrument score of ≥ 2.5
• If on medication for painful diabetic peripheral neuropathy (other than gabapentin or pregabalin), must have been on a stable dose defined as < 50% change in total dose over 3 months prior to completion of informed consent
• Male participants and their female partners had to agree to use double-barrier contraception during the study or provide proof of postmenopausal state (minimum 1 year) or surgical sterility
• Male participants were not to donate sperm during the study
• Female participants had to be nonpregnant, nonlactating, and either postmenopausal for at least 1 year, or surgically sterile for at least 3 months, or agreed to use double-barrier contraception from 28 days prior to randomization and/or their last confirmed menstrual period prior to study randomization (whichever is longer) until the end of the study
• Capable and willing to comply with the requirements and restrictions of the protocol and informed consent form
• Able to complete all screening activities within 52 days of signing the informed consent form

Ki nem vehet részt

• Had taken gabapentin or pregabalin during 30 days before completion of informed consent process or was going to take at any time during the study
• Systolic blood pressure >180 mmHg on tolerable doses of standard antihypertensive medications at Screening determined by the Investigator to preclude participation
• Hyperlipidemia or dyslipidemia not being treated with an optimal treatment regimen that follows the Standards of Care for hyperlipidemic/dyslipidemic patients with DM
• Stroke or cerebrovascular accident or myocardial infarction within 3 months before Screening
• Progressive renal dysfunction, defined as a decrease in estimated glomerular filtration rate to chronic kidney disease Stage 1, 2, or 3 in the past 6 months before Screening
• Any prior or planned lower extremity amputation (excluding toe amputations) due to diabetic complications or prior lower leg injury (e.g., scarring, muscle atrophy) in the calf area (gastrocnemius) that would significantly reduce the surface area of the skin or amount of intact skeletal muscle required for the 16 treatment injections of Engensis
• Immunosuppression due to underlying disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) or to currently receiving immunosuppressive drugs, (e.g., chemotherapy, corticosteroids) or to radiation therapy
• Participants requiring chronic oral or injectable steroids and unwilling to refrain from taking these drugs for the duration of the study
• Participants with a prior history of stem cell transplant for cancer no matter how long they have been cancer-free
• Participants unwilling to discontinue their use of the following during Screening at least 7 days before starting eDiary entries and not use any of the following during the study:; skeletal muscle relaxants; opioids; transcutaneous electrical nerve stimulation (tens); acupuncture; benzodiazepines (other than stable bedtime dose); injectable or oral steroids
• Participants not on a stable dose and not willing to remain on a stable dose during study for the following drugs:; antidepressants; antiepileptics; duloxetine
• Participants using the following medications and unwilling to discontinue topical use on the lower legs and feet and throughout the study:; capsaicin; anesthetic creams (except during Study Injections); anesthetic patches; isosorbide dinitrate spray
• Use of an investigational drug or treatment in past 30 days or previous participation in a clinical study with Engensis
• Peripheral neuropathy caused by a condition other than diabetes: e.g., anatomic (sciatic nerve compression), systemic (monoclonal gammopathy), metabolic (thyroid disease), and toxic (alcohol use) neuropathies
• Progressive or degenerative neurological disorder, such as amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, vascular dementia, multiple sclerosis, or other neurological disorders determined by the Investigator to preclude participation
• Symptomatic peripheral artery disease or peripheral artery disease requiring revascularization and/or that may interfere with the conduct of the study
• Vasculitis, such as from Buerger's or other diseases
• Class 3 or 4 heart failure
• Estimated glomerular filtration rate < 30 mL/min/1.73 m2 using the chronic kidney disease epidemiology collaboration formula based on Cystatin C levels
• Ophthalmologic conditions pertinent to signs or symptoms of proliferative diabetic retinopathy or other ocular conditions that precluded standard ophthalmologic examination
• Active infection requiring antimicrobial agent(s) (chronic infection or severe active infection that may compromise the Participant's well-being or participation in the study, in the Investigator's judgment)
• Chronic inflammatory or autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis)
• Participants with a family medical history of 2 or more first-degree relatives (parent, sibling, child) diagnosed to have the same type of cancer - breast cancer, cervical cancer, colon cancer, endometrial cancer, lung cancer, or prostate cancer; or with a family medical history of Lynch Syndrome (hereditary non-polyposis colorectal cancer) in any first-degree relative; or who show positive results during cancer screening
• Active acute or chronic hepatitis B
• Active hepatitis C
• History of drug abuse (the habitual taking of addictive or illegal drugs) in the past 3 months and positive for Drugs of Abuse, with the exception of cannabis, during Screening
• Recent treatment for COVID-19 with ongoing sequelae
• Clinically significant laboratory values or current medical conditions during Screening that, in the judgment of the Investigator, should be exclusionary
• Participants with cancer who have not been cancer-free for ≥5 years with the following exceptions (not excluded): Participants with in-situ basal cell or squamous cell carcinoma
• Other sources of pain that prevented accurate assessment of diabetic peripheral neuropathy pain (e.g., thoracic and/or lumbar root proximal neuropathy, mononeuritis multiplex)
• Symptomatic bradycardia or untreated high degree atrioventricular block
• Myopathy (e.g., Duchenne or Becker muscular dystrophy, polymyositis)
• Positive human immunodeficiency virus or human T-cell lymphotropic virus I/II test at Screening
• Hospital Anxiety and Depression Scale score of ≥ 15 on either subscale
• Body mass index ≥ 42 kg/m2