A Study to Investigate Safety and Effectiveness of Porcine Pancreatic Cells (OPF-310) in Patients With Type 1 Diabetes Mellitus

Exclusion Criteria

• •1. Previous history of insulin resistance (defined as an average insulin dose requirement ≥ 0.8 unit/kg/day for 1 week prior to enrollment).
• •2. Subject has latent autoimmune diabetes in adults (LADA), ketosis-prone (Flatbush) diabetes, or maturity onset diabetes of the young (MODY).
• •3. CRP ≥ 10 mg/L.
• •4. Clinically unstable thyroid disease (thyroid stimulating hormone (TSH)\< the lower limit of the normal range of TSH at the site.) Patients with subclinical hyperthyroidism can be rescreened once TSH levels normalize due to treatment or other factors. In addition, patients with transiently abnormal TSH levels may undergo rescreening only once during the screening period.
• •5. History of malignancies within the past 5 years, excluding basal and squamous cell carcinoma
• •6. Positive serologies or nucleic acid testing for human immunodeficiency virus (HIV), hepatitis C, and hepatitis B.
• •7. Active or untreated proliferative diabetic retinopathy. Subjects may be rescreened once they are successfully treated.
• •8. Serious comorbid conditions that are likely to affect participation in the study, including:
• •1. Within the last 12 months, peripheral vascular disease with previous amputation.
• •2. History of New York Heart Association (NYHA) class II, III or IV congestive heart failure (CHF) and/or chronic atrial fibrillation.
• •3. Chronic obstructive pulmonary disease (COPD) or asthma with previous hospitalization for decompensation; a requirement for mechanical ventilation at any stage; or long- term treatment with oral corticosteroids.
• •4. Macroalbuminuria (\> 300 mg albumin/gm creatinine).
• •5. Estimated glomerular filtration rate (eGFR) cut-off of \< 30 ml/min for all per Kidney Disease Improving Global Outcomes (KDOQI) and Kidney Disease Outcomes Quality Initiative (KDIGO) consensus.
• •9. Use of warfarin or other anticoagulant therapy (except aspirin), or prothrombin time and international normalized ratio (PT-INR) \> 1.5
• •10. Adrenal insufficiency being treated with corticosteroids
• •11. Previous pan-peritonitis
• •12. Previous cardiovascular or cerebrovascular disease. NOTE: For the purposes of this exclusion criterion, "previous cardiovascular disease" is defined as the presence of co-existing cardiac disease, characterized by any of the following conditions:
• •1. Recent myocardial infarction (within past one year), or
• •2. Angiographic evidence of non-correctable coronary artery disease, or
• •3. Evidence of ischemia on functional cardiac exam (with a stress echo test recommended for subjects with a history of ischemic disease), or
• •4. Heart failure \> NYHAII
• •13. Patients with hematopoietic stem cell abnormalities (e.g., aplastic anemia, myelodysplastic syndrome)
• •14. Patients who received a blood transfusion in the previous 90 days, are anticipated to undergo surgery during the 1-year study period that may require transfusion, or have donated blood within the previous 90 days.
• •15. Previous receipt of an organ, skin allograft, or other tissue transplant from an allogeneic human or animal donor.
• •16. Treatment with immunosuppressive medication.
• •17. Previous abdominal surgery, excluding uncomplicated appendectomy, cholecystectomy, exploratory laparoscopy and hernia repair performed prior to 12 weeks prior to enrollment.
• •18. Treatment with any hypoglycemic medication prescribed for glycemic control, other than insulin therapy.
• •19. Treatment with acetaminophen or hydroxycarbamide.
• •20. Use of any investigational products within 12 weeks of enrollment (before entering run-in) or 5 half-lives of the investigational product, whichever is greater.
• •21. Subject has history of allergy to antibiotics (Amphotericin B, Cefazolin, Ciprofloxacin, Gentamicin), which are used during manufacture of OPF-310.
• •22. Previous history of insulin allergy (including porcine insulin), pork product allergy or alginate/seaweed allergy.
• •23. Panel reactive antibodies (PRA) \> 80 %.
• •24. Active drug, substance or alcohol addiction.
• •25. Body mass index (BMI) \>27 kg/m2.
• •26. Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, psychiatric disorder, medical condition, or a history of non-adherence to appointments or treatments