Efficacy and Safety of Everolimus Versus Mycophenolate Mofetil in Liver Transplant Recipients.

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of CertiroBell® tablet compared with mycophenolate mofetil in primary living donor liver transplant recipients.

Detailed Description
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This study is multi-center, open-label, randomized controlled phase 4 study to evaluate the efficacy and safety of certirobell® tablet compared with mycophenolate mofetil in primary living donor liver transplant recipients. On the first visit the patients scheduled to be operated liver transplant in 35 days will be conducted screening. Patients who meet the criteria of this clinical trial will be randomized to CertiroBell or mycophenolate mofetil on the second visit. Each group will take CertiroBell or mycophenolate mofetil and will conduct scheduled tests with 5 additional visits.

Official Title
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Multi-center, Open-label, Randomized Controlled Phase 4 Study to Evaluate the Efficacy and Safety of CertiroBell® Compared With Mycophenolate Mofetil in Primary Living Donor Liver Transplant Recipients.

Conditions
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Liver Transplant

Intervention / Treatment
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* Drug: Everolimus Tab.
* Drug: Mycophenolate mofetil Tab./Cap.


Participation Criteria
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Eligibility Criteria
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* Inclusion Criteria: [Time of screening] Patients who have transplanted in primary living donor liver in 35 days or who plan to be transplanted in primary living donor liver. Over 20 years old(male or female) Agreement with written informed consent [Time of randomization] - Patients who have transplanted liver within 4 weeks(25 days to 35 days) * Exclusion Criteria [Time of screening] Patients who have transplanted non-liver organs or have plan to be transplanted non-liver organs. Patients with bioartificial liver (cell system) Patients who diagnosed with malignant tumor within 5 years [however, who have recovered from skin cancer (squamous cell/basal cell carcinoma) or thyroid cancer, hepatocellular carcinoma without main vessel invasion or extrahepatic metastasis can be enrolled] Patients with severe systemic infection Women who are pregnant or breast feeding or not agree to the proper use of contraception during the trial Participated in other trial within 4 weeks In investigator's judgement [Time of randomization] Patients with acute rejection who have been clinically treated after liver transplantation. Patients with complication related to the hepatic artery such as hepatic artery thrombosis at the time of randomization. At screening WBC <1,500/mm^3 or PLT <30,000/mm^3 or over 3 times upper than normal range of liver function tests(T-bilirubin, AST, ALT) levels Protein/Creatinine ratio(urine test) > 1 or eGFR by MDRD< 30mL/min/1.73m^2 or Total cholesterol > 350mg/dL or triglycerides > 500mg/dL Patients taking HCV(hepatitis C virus) Therapeutic Drugs Patients who had plasmapheresis within 1 week. Patents who had a record of taking mTOR inhibitor before. In investigator's judgement

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CertiroBell Tablet<br>De novo liver transplant recipients will be randomized after liver transplant operation. | Drug: Everolimus Tab.<br>* After first dose 1mg BID(total 2mg daily PO), check the blood concentration of everolimus at each visit and adjust the dose to acheive the blood concentration maintaining at 3 8ng/mL.<br>* Other names: CertiroBell Tab.;|
| Active Comparator: Mycophenolate mofetil Tablet/Capsule<br>De novo liver transplant recipients will be randomized after liver transplant operation. | Drug: Mycophenolate mofetil Tab./Cap.<br>* Up to 1.5g BID(total 3g daily), PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of composite efficacy failure | composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure | until 24 weeks after taking medicine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of biopsy-confirmed acute rejection | acute rejection confirmed by result of biopsy(over 4 points of RAI score) | until 24weeks and 48weeks after taking medicine | 
| The pathological results and time of occurrence and method of treatment, result of the treatment of acute rejection confirmed by biopsy(over 4 points of RAI score) | details of acute rejection confirmed by result of biopsy(over 4 points of RAI score) | until 24weeks and 48weeks after taking medicine | 
| Incidence of composite efficacy failure | composite efficacy failure include biopsy-confirmed acute rejection, graft loss, death, or follow-up failure | until 48weeks after taking medicine | 
| Survival rate of patients | Survival rate of patients | until 24weeks and 48weeks after taking medicine | 
| Survival rate of transplanted organ | Survival rate of transplanted organ | until 24weeks and 48weeks after taking medicine | 
| Incidence and recurrence rates of liver cancer | Incidence and recurrence rates of liver cancer | until 24weeks and 48weeks after taking medicine | 
| Incidence and recurrence rates of HCV infection | Incidence and recurrence rates of HCV infection | until 24weeks and 48weeks after taking medicine | 
| Incidence of CMV infection | Incidence of CMV infection | until 24weeks and 48weeks after taking medicine | 
| variation of Serum creatinine, eGFR(estimated glomerular filtration rate) compared to the baseline | eGFR using MDRD(Modification of Diet in Renal Disease) method | at 24 weeks and 48weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Everolimus, CertiroBell, Mycophenolate mofetil