Efficacy and Safety of CertiroBell® Tablet Plus Tacrolimus in Primary Living Donor Liver Transplant Recipients

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of CertiroBell® tablet plus tacrolimus

Detailed Description
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This study is multi-center, single arm, open-label, phase 4 study to evaluate the efficacy and safety of CertiroBell® tablet plus tacrolimus in primary living donor liver transplant recipients.

Official Title
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Multi-center, Single Arm, Open-label, Phase 4 STudy to Evaluate the Efficacy and Safety of CertiroBELL® Tablet Plus TAcrolimus in Primary Living Donor Liver Transplant Recipients

Conditions
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Liver Transplant

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who had liver transplantation from living donor and had passed over 3 months since operation. Over 20 years old Patients who are being treated with Tacrolimus at screening visit Patients who agreed to written informed consent Exclusion Criteria: Patients who had received non-liver organs before liver transplantation or had received other organs while receiving liver. Patients who had auxiliary partial orthotopic liver transplantation or had bioartifical liver Patients who have been diagnosed with acute rejection within 6 months and have been treated Patients who had hepatic artery complication such as hepatic artery thrombosis within recent 6 months Patients who have been diagnosed with malignant tumor within 5 years(however, the following will be excepted) fully recovered from skin cancer(squamous cell/basal cell carcinoma or thyroid cancer) haptocellular carcinoma without main vessel invasion Patients with severe systemic infection Patients who are difficult to communicate due to mental disorder Patients who are in treatment for hapatitis, or are over 3 times higher than upper normal limit in liver function test(T-bilirubin, AST, ALT) or over 5 times higher than normal limit of ALP Patients who are(at screening visit) WBC<1,500/mm^3 PLT<30,000/mm^3 over 1.0 in Protein/creatinine ratio(UA test) eGFR<30mL/min/1.73m^2(MDRD) Total Cholesterol>350mg/dL or Triglycerides>500mg/dL Patients taking HCV(hapatitis C virus) therapeutic drug or anti-HCV positive patients who have positive result in HCV RNA test at screening visit Patients who had plasmapheresis within 1 week Those who are pregnant, nursing, or are not practicing contraception with appropriate method Patients who had plasmapheresis within 3 months if participated in other trail within 4 weeks(28 days) 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CertiroBell Tablet<br>Use in combination with Tacrolimus at least 6 months after liver transplantation. | Drug: Everolimus<br>* - Oral intake, BID - After first dose 1mg(total 2mg daily), check the blood concentration of everolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 3 8mg/mL.<br>* Other names: CertiroBell Tab.;|

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 24 weeks after taking medicine | 
| Pathological result, time of occurrence, treatment method and treatment result of acute rejection confirmed by biopsy(over 4 points of RAI score) | details of acute rejection confiremd by result of biopsy(over 4 points of RAI score) | until 24 weeks after taking medicine | 
| Survival rate of patients | Survival rate of patients | until 24 weeks after taking medicine | 
| Survival rate of transplanted organ | Survival rate of transplanted organ | until 24 weeks after taking medicine | 
| Incidence rate of liver cancer | Incidence rate of liver cancer | until 24 weeks after taking medicine | 
| Recurrence rate of liver cancer | Recurrence rate of liver cancer | until 24 weeks after taking medicine | 
| Incidence rate of CMV infection | Incidence rate of CMV infection | until 24 weeks after taking medicine | 
| Variation of serum creatinine, eGFR(estimated glomerular filtration rate) compared to baseline using MDRD(Modification of Diet in Renal Disease) | eGRF using MDRD(Modification of Diet in Renal Disease) method | until 24 weeks after taking medicine | 

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