A Phase I/II Study of the Safety and Efficacy of Sernova's Cell PouchTM for Therapeutic Islet Transplantation

Exclusion Criteria

• •1. Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent myocardial infarction (within past 6 months); (b) left ventricular ejection fraction \<30%; or (c) evidence of ischemia on functional cardiac exam.
• •2. Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to transplant).
• •3. Psychiatric disorder making the subject not a suitable candidate for transplantation, (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
• •4. History of non-adherence to prescribed regimens.
• •5. Active infection including Hepatitis C, Hepatitis B, HIV, TB (subjects with a positive PPD performed within one year of enrollment, and no history of adequate chemoprophylaxis).
• •6. Any history of or current malignancies except squamous or basal skin cancer.
• •7. BMI \> 35 kg/m2 at screening visit.
• •8. Age less than 18 or greater than 68 years.
• •9. Measured glomerular filtration rate (GFR) \<60 mL/min/1.73 m2.
• •10. Presence or history of macroalbuminuria (\>300 mg/g creatinine).
• •11. Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
• •12. Baseline Hb \< 105g/L in women, or \< 120 g/L in men.
• •13. Baseline screening liver function tests outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values \>1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
• •14. Untreated proliferative retinopathy.
• •15. Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding.
• •16. Previous transplant or evidence of significant sensitization on PRA (at the discretion of the investigator).
• •17. Insulin requirement \>1.0 U/kg/day
• •18. HbA1C \>12%.
• •19. Uncontrolled hyperlipidemia \[fasting LDL cholesterol \> 3.4 mmol/L, treated or untreated; and/or fasting triglycerides \> 2.3 mmol/L\].
• •20. Under treatment for a medical condition requiring chronic use of steroids.
• •21. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR \> 1.5.
• •22. Untreated Celiac disease.
• •23. Patients with Graves disease will be excluded unless previously adequately treated with radioiodine ablative therapy.
• •24. Any medical condition that, in the opinion of the clinical investigator, will interfere with the safe participation in the trial.