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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01888432
• Date of registration: 15/06/2013
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants
• Scientific title: 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 and Long Term Extension to Evaluate the Efficacy and Safety of Concentration-controlled Everolimus Plus Reduced Tacrolimus Compared to Standard Tacrolimus in Recipients of Living Donor Liver Transplants in Japan
• Date of first enrolment: September 25, 2013
• Target sample size: 285
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01888432
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Care Provider).
• Phase: Phase 3

Countries of recruitment

Canada, Egypt, Germany, India, Italy, Japan, Korea, Republic of, Russian Federation, Saudi Arabia, Singapore, Taiwan, Turkey, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Liver Transplantation

Intervention(s)

Drug: Standard tacrolimus

Drug: Everolimus + reduced tacrolimus

Primary Outcome(s)

Number of Participants With Composite Efficacy Failure of Treated Biopsy Proven Acute Rejection, Graft Loss or Death in Everolimus With Reduced Tacrolimus Group Compared to Standard Tacrolimus [Time Frame: 12 months post transplantation]

Secondary Outcome(s)

Number of Subjects Experiencing Adverse Events/Infections by SOC [Time Frame: Month 24]

Compare Incidence of Graft Loss [Time Frame: Month 12 and Month 24 post transplantation]

Compare Incidence of AR [Time Frame: Month 12 and Month 24 post transplantation]

Compare Incidence of BPAR [Time Frame: Month 12 and Month 24 post transplantation]

Number of Participants With Time to Recurrence of HCC in Subjects With a Diagnosis of HCC at the Time of Liver Transplantation [Time Frame: Month 12 and Month 24]

Renal Function by Estimated Glomerular Filtration Rate (eGFR) From Randomization [Time Frame: From randomization to month 12]

Compare Incidence of Death [Time Frame: Month 12 and Month 24 post transplantation]

Number of Participants With Composite of tBPAR, Graft Loss, and Death [Time Frame: Month 24 post transplantation]

Compare Incidence of a Composite of Death or Graft Loss [Time Frame: Month 12 and Month 24 post transplantation]

Compare Incidence of tBPAR [Time Frame: Month 12 and Month 24 post transplantation]

Composite Efficacy Failure of Treated Biopsy in Everolimus With Reduced Tacrolimus Group Compared to Standard Tacrolimus in Patients From Japan Only [Time Frame: randomization, 36 months post transplantion]

Compare Incidence of tAR [Time Frame: Month 12 and Month 24 post transplantation]

Compare Renal Function Over Time Assessed by the Change by eGFR, Post-randomization [Time Frame: From randomziation to month 24]

Compare Incidence of Notable Safety Events (SAEs, Infections and Serious Infections Leading to Premature Discontinuation) [Time Frame: Month 24]

Renal Function by Estimated Glomerular Filtration Rate (All Extension Patients) [Time Frame: randomization, at 36 months post transplantation]

Secondary ID(s)

CRAD001H2307

2010-024527-25

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 13/11/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01888432