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

Inclusion Criteria

• 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 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
• Class 3 or 4 heart failure
• Symptomatic bradycardia or untreated high degree atrioventricular block
• Stroke or cerebrovascular accident or myocardial infarction within 3 months before Screening
• Estimated glomerular filtration rate < 30 mL/min/1.73 m2 using the chronic kidney disease epidemiology collaboration formula based on Cystatin C levels
• 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
• Ophthalmologic conditions pertinent to signs or symptoms of proliferative diabetic retinopathy or other ocular conditions that precluded standard ophthalmologic examination
• Myopathy (e.g., Duchenne or Becker muscular dystrophy, polymyositis)
• 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
• 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)
• 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 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
• Positive human immunodeficiency virus or human T-cell lymphotropic virus I/II test at Screening
• 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
• Participants with a prior history of stem cell transplant