A 24 Month, Randomized, Controlled, Study to Evaluate the Efficacy and Safety of Concentration-controlled Everolimus Plus Reduced Tacrolimus Compared to Standard Tacrolimus in Recipients of Living Donor Liver Transplants

Inclusion Criteria

Inclusion criteria:

- Written informed consent

- Subject aged ≥18 years of a primary, orthotopic liver allograft, from a living donor

- Subject negative for HIV

Inclusion criteria at Randomization:

- Subject was initiated 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 of 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 artery, major/reconstructed hepatic vein, 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 mmol/L) or
hypertriglyceridemia (>500 mg/dL; >8.5 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. Other protocol-defined
inclusion/exclusion criteria may apply.