Study of the Effect of Everolimus Immunosuppressive Combination Therapies on Renal Function When Used as a Maintenance Treatment for Liver Transplant Patients.

Study Overview
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Brief Summary
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A 24-month multi-center, open-label, randomized, controlled study to evaluate the evolution of renal function in maintenance liver transplant recipients receiving everolimus plus reduced TAC or everolimus plus mycophenolate mofetil (MMF)

Official Title
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A 24-month Multi-center, Open-label, Randomized, Controlled Study to Evaluate the Evolution of Renal Function in Maintenance Liver Transplant Recipients Receiving Either RAD001 (Everolimus) Plus Reduced TAC or RAD001 (Everolimus) Plus Mycophenolate Mofetil (MMF)

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: TAC withdrawal
* Drug: Everolimus with reduced TAC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients willing and capable of providing written informed consent for study participation. Adults 18 to 70 years of age. Liver allograft from a deceased or living donor. Treated with a CNI containing immunosuppressive regimen. Liver transplant 6 to 24 months prior to screening. Estimated kidney function between chronic kidney disease (CKD) IIIb/ 30 mL/min < eGFR < CKD II/60 mL/min with deteriorating renal function. Acceptable graft function (according to liver enzymes (AST / ALT) and total bilirubin). Exclusion Criteria: Multiple solid organ transplant recipients Active chronic inflammatory bowel disease and recurrent autoimmune hepatitis Malignant diseases other than neoplasms of the skin. Patient on other investigational drug or presence of any hypersensitivity to the interventional drug. Pregnant or nursing (lactating) women. Women of child-bearing potential (physiologically capable of becoming pregnant, unless they are using effective methods of contraception). Anemia, thrombocytopenia, leucopenia, uncontrolled hyperlipidemia or proteinuria HIV positivity Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Everolimus with MMF (TAC-withdrawal)<br>Everolimus (RAD001) with MMF and Steroids | Drug: TAC withdrawal<br>* Everolimus (RAD001) with MMF and Steroids<br>|
| Active Comparator: Everolimus with reduced TAC<br>Everolimus (RAD001) with reduced TAC and Steroids | Drug: Everolimus with reduced TAC<br>* Active comparator arm: Everolimus (RAD001) with reduced TAC and Steroids<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function | The primary variable will be the mean change in renal function assessed by eGFR from randomization to Month 6. | Randomization to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy (tBPAR, graft loss, death, loss to follow-up) | Composite efficacy failure of tBPAR, graft loss, death or loss to follow-up and each of its components at month 6 will be analysed per event rate estimates, Kaplan-Meier and regression models. The time to the first occurrence of the event will be calculated from the randomization date. | To Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open-label, randomized, calcineurin-inhibitor, CNI, tacrolimus, MMF, maintenance liver transplant, RAD001H, CRAD001H, liver transplant, transplantation