Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants

Inclusion criteria

• Written informed consent
• Subject aged ≥18 years of a primary, orthotopic liver allograft, from a living donor
• Subject negative for HIV

Incusion criteria at Randomization:

• Subject was initated on tacrolimus-based immunosuppressive regimen with steroids and other immunosuppression

Exclusion criteria

• Subjects transplanted for acute liver failure
• HCV negativesubjects receiving a transplant from HCV positive donor
• Subjects receiving multiple solid organ (including multiple liver lobes/segments) or islet cell tissue transplants, or have previously received an organ or tissue transplant.
• Subjects receiving an ABO incompatible allograft.
• MELD-score > 35 within 1 month prior to transplantation.
• Use of immunosuppressive or antibody induction agents not specified in the protocol.
• History of malignancy of any organ system (except hepatocellular carcinoma or localized basal cell carcinoma of the skin)
• Hepatocellular carcinoma with extrahepatic spread or macrovascular invasion
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 2 weeks after the last dose of study medication
• History of hypersensitivity to any of the study drugs or to drugs with similar chemical class, or to any of the excipients

Exclusion criteria at Randomization:

• Any post-transplant history of thrombosis, occlusion or stent placement in any major hepatic arteries, hepatic veins, portal vein or inferior vena cava at any time during the run-in period prior to randomization.
• Subjects with a confirmed spot urine protein/creatinine ratio that indicates ≥ 1.0 g/24 hrs of proteinuria
• Subjects who have severe hypercholesterolemia (>350 mg/dL; >9.1 mmol/L) or hypertriglyceridemia (>500 mg/dL; >5.6 mmol/L) at randomization.
• Subjects with platelet count < 30,000/mm3.
• Subjects with an absolute neutrophil count of < 1,000/mm³ or white blood cell count of < 2,000/mm³.
• Subjects with systemic infection requiring active use of IV antibiotics.
• Subjects requiring life support measures such as ventilation, dialysis, vasopressor agents.
• Subjects who require renal replacement therapy within 7 days prior to randomization.
• Subjects with detectable HBV DNA at time of randomization
• Subjects meeting the following criteria for acute rejection during the run in period:
• Any acute rejection in the week prior to randomization.
• 2 treated acute rejections.
• Any rejection requiring antibody treatment.
• Any severe cellular (and/or any humoral) rejection.

Long term extension for patients in Japan:

Inclusion criteria

• Written informed consent must be obtained before any extension specific assessment is performed.
• Ability and willingness to adhere to study regimen.
• Completed Month 24 visit of core study and continuously being treated with assigned regimen.

Exclusion criteria

• Use of medication that is prohibited by the study protocol at Month 24.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• History of hypersensitivity to any of the study drugs or to drugs with similar chemical class, or to any of the excipients