Study to Assess Safety and Efficacy of Engensis in Painful Diabetic Peripheral Neuropathy (REGAiN-1A)

This is an interventional treatment trial for Diabetic Neuropathy, Painful Read More

Inclusion Criteria

1. Male or female participants age ≥ 18 years at time of completion of the informed consent process
2. Type 1 or 2 diabetes mellitus (DM) 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
3. Glycosylated hemoglobin A1c (HbA1c) of ≤ 10.0% using the first assessment collected during Screening
4. Documented diagnosis of bilateral painful DPN in both lower extremities at least 6 months prior to Screening
5. An Average Daily Pain Score ≥ 4 (standard deviation ≥ 0.3 and ≤ 1.5) that is completed during the 7 days prior to randomization (Day 0)
6. The physical examination component of the Michigan Neuropathy Screening Instrument (MNSI) score of ≥ 2.5
7. If on medication for painful DPN (other than gabapentin or pregabalin), must be on a stable dose defined as < 50% change in total dose over 3 months prior to completion of informed consent process
8. Male participants and their female partners must agree to use double-barrier contraception during the study or provide proof of postmenopausal state (minimum 1 year) or surgical sterility
9. Male participants must not donate sperm during the study
10. Female participants must be nonpregnant, nonlactating, and either postmenopausal for at least 1 year, or surgically sterile for at least 3 months, or agree 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
11. Capable and willing to comply with the requirements and restrictions of the protocol and informed consent form
12. Able to complete all screening activities within 45 days of signing the informed consent form

Exclusion Criteria

1. Other sources of pain that would prevent accurate assessment of DPN pain (e.g., thoracic and/or lumbar root proximal neuropathy, mononeuritis multiplex)
2. 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
3. Has taken gabapentin or pregabalin during 30 days before completion of informed consent process or will take at any time during the study
4. Progressive or degenerative neurological disorder, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, vascular dementia, multiple sclerosis, or other neurological disorders determined by the Investigator to preclude participation
5. Symptomatic peripheral artery disease (PAD) or PAD requiring revascularization and/or that may interfere with the conduct of the study
6. Vasculitis, such as from Buerger's or other disease
7. Systolic blood pressure >180 mm Hg on tolerable doses of standard antihypertensive medications at Screening determined by the Investigator to preclude participation
8. Hyperlipidemia or dyslipidemia not being treated with an optimal treatment regimen that follows the Standards of Care for hyperlipidemic/dyslipidemic patients with DM
9. Class 3 or 4 heart failure
10. Symptomatic bradycardia or untreated high degree atrioventricular block
11. Stroke or cerebrovascular accident or myocardial infarction within 3 months before Screening
12. eGFR < 30 mL/min/1.73 m2
13. Progressive renal dysfunction, defined as a decrease in eGFR to chronic kidney disease (CKD) Stage 1, 2, or 3 in the past 6 months before Screening
14. Ophthalmologic conditions pertinent to signs or symptoms of proliferative diabetic retinopathy (PDR) or other ocular conditions that preclude standard ophthalmologic examination
15. Myopathy (e.g., Duchenne or Becker muscular dystrophy, polymyositis)
16. 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
17. 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)
18. Chronic inflammatory or autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis)
19. 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
20. Participants requiring chronic oral or injectable steroids and unwilling to refrain from taking these drugs for the duration of the study
21. 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
22. Positive human immunodeficiency virus (HIV) or human T-cell lymphotropic virus (HTLV) I/II test at Screening
23. Participants 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
24. Participants with a prior history of stem cell transplant for cancer no matter how long they have been cancer-free
25. Active acute or chronic hepatitis B
26. Active hepatitis C
27. Clinically significant laboratory values or current medical conditions during Screening that, in the judgment of the Investigator, should be exclusionary
28. Hospital Anxiety and Depression Scale (HADS) score of ≥ 15 on either subscale
29. 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

30. 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

31. Participants not on a stable dose and not willing to remain on a stable dose during the study for the following drugs:

    • antidepressants
    • antiepileptics
    • duloxetine

32. Participants currently 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
    • ISDN spray
33. Use of an investigational drug or treatment in past 30 days or previous participation in a clinical study with Engensis
34. Body mass index (BMI) ≥ 42 kg/m2
35. Recent treatment for COVID-19 with ongoing sequelae