Status:

COMPLETED

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

Lead Sponsor:

Novartis Pharmaceuticals

Conditions:

Liver Transplantation

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

The purpose of this trial was to demonstrate the efficacy and safety of everolimus in combination with reduced tacrolimus, compared to tacrolimus control, in living donor liver transplant recipients.

Detailed Description

This study was 24 month, multicenter study in 280 living donor liver transplant patients from Asia, Europe and Canada. The study has an long term extension in Japan and approximately 28 patients were ...

Eligibility Criteria

Inclusion

  • 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

Exclusion

    Key Trial Info

    Start Date :

    September 25 2013

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    April 21 2018

    Estimated Enrollment :

    285 Patients enrolled

    Trial Details

    Trial ID

    NCT01888432

    Start Date

    September 25 2013

    End Date

    April 21 2018

    Last Update

    March 18 2019

    Active Locations (42)

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    Page 1 of 11 (42 locations)

    1

    Novartis Investigative Site

    Los Angeles, California, United States, 90033

    2

    Novartis Investigative Site

    San Francisco, California, United States, 94143

    3

    Novartis Investigative Site

    Baltimore, Maryland, United States, 21201

    4

    Novartis Investigative Site

    Boston, Massachusetts, United States, 02114