EVR and EPO for Liver Transplant Tolerance

Exclusion Criteria

• •1. Inability of a subject to comply with study protocol
• •2. Any medical condition requiring chronic systemic corticosteroid, e.g., severe reactive airways disease. Use of inhaled steroids is not an exclusion
• •3. Autoimmune cause of liver disease (including autoimmune hepatitis (AIH), primary sclerosing cholangitis, primary biliary cirrhosis)
• •4. Diagnosis of rejection within 52 weeks prior to screening
• •5. Donor human leukocyte antigen (HLA) typing unavailable or inadequate for assigning donor-specific antibody (DSA)
• •6. Need for uninterrupted anticoagulation
• •7. Known active current or history of invasive fungal infection, or mycobacterial infection within 1 year prior to screening
• •8. Human immunodeficiency virus (HIV)-positive
• •9. Serious uncontrolled concomitant major organ disease
• •10. Recipient of non-liver solid organ or bone marrow transplant
• •11. Any infection requiring hospitalization and IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
• •12. Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated in situ cervical cancer. History of hepatocellular carcinoma in the explanted liver is acceptable provided that
• •1. the last alpha fetoprotein obtained within 3 months prior to liver transplantation was \< 400 microg/L, and
• •2. the recipients' explanted liver did not have evidence of increased risk of recurrent cancer, i.e., explant was within the Milan criteria, with no vascular invasion, and with no cholangiocarcinoma morphology
• •13. Neutropenia (absolute neutrophil count or ANC \<1000 microliter) within 4 weeks prior to study enrollment
• •14. History of hypersensitivity to Epoetin (EPO) or mammalian Target of Rapamycin inhibitor (mTOR-I)
• •15. History of angioedema
• •16. History of hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. History of lactose intolerance is not an exclusion
• •17. History of genetic disorders predisposing to thrombosis including but not limited to Factor V Leiden mutation, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin III deficiency
• •18. History of venous or arterial thrombosis or thromboembolism, acute MI, or thrombotic stroke except for a history of isolated portal vein thrombosis in the setting of hepatic cirrhosis
• •19. History of Budd Chiari syndrome
• •20. Hemoglobin \> 13.5 g/dl
• •21. Plasma fibrinogen or D-dimer level \> ULN
• •22. Planned major surgery within the next 12 months
• •23. Uncontrolled severe hypertension
• •24. Uncontrolled clinically significant cardiac arrhythmia
• •25. Proteinuria with urine protein/creatinine \>0.5 g/g
• •26. Severe hyperlipidemia with total cholesterol \>350 mg/dl or triglycerides \>1000 mg/dl
• •27. Current alcohol, drug, or chemical dependency
• •28. Currently pregnant or nursing
• •29. Current treatment with an estrogen-containing oral contraceptive, or systemic estrogen replacement therapy
• •30. Treatment with an immunomodulatory biological drug within 12 weeks of study entry
• •31. Immunization with live vaccine within 2 weeks of study baseline visit
• •32. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
• •33. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study