Phase 3b Study to Evaluate Advagraf in Combination With Mycophenolate Mofetil and Basiliximab in Liver Transplantation

Study Overview
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Brief Summary
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Comparison of 3 dosing regimens of Advagraf to determine if there is a dosing regimen which may have the potential to cause fewer kidney problems.

Official Title
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A Multicenter, Three Arm, Randomized, Open Label Clinical Study to Compare Renal Function in Liver Transplant Recipients Receiving an Immunosuppressive Regimen of Advagraf (Immediately or Delayed Post-transplant) and MMF With or Without a Monoclonal Anti-IL2R Antibody (Basiliximab)

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Advagraf
* Drug: Mycophenolate Mofetil
* Drug: Basiliximab
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing orthotopic liver or split liver allograft transplantation Female subject of childbearing potential must have a negative serum or urine pregnancy test at enrollment and must agree to maintain effective birth control during the study Exclusion Criteria: Receiving a multi-organ transplant or having previous received an organ transplant (including liver re-transplantation) Receiving an auxiliary graft or in whom a bio-artificial liver (cell system) has been used Receiving ABO incompatible graft or a graft from a non heart beating donor Ongoing dosing with systemic corticosteroids Subjects with systemic infection requiring treatment except viral hepatitis Diagnosis of new-onset malignancy prior to transplantation, with the exception of basocellular or squamous cell carcinoma of the skin which had been treated successfully. However, subjects with primary liver carcinoma can be included if they meet the following criteria: < 3 nodes no node larger than 5 cm no metastases no vascular tumoral invasion Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or active peptic ulcer Subject or donor known to be HIV positive Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids, basiliximab or mycophenolate mofetil or any of the product excipients Pregnant woman or breast-feeding mother Currently participating in another clinical trial, and/or has taken an investigational drug within 28 days prior to enrollment Unlikely to comply with the Visits scheduled in the protocol Any unstable medical condition that could interfere with the study objectives in the opinion of the Investigator Receiving prohibited concomitant therapy, or received prohibited concomitant therapy within 28 days prior to enrollment Any form of substance abuse, psychiatric disorder or condition which, in the opinion of the Investigator, may complicate communication with the Investigator

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: Dosing Regimen 1<br>Advagraf + MMF + Corticosteroids (Bolus) | Drug: Advagraf<br>* Capsule<br>* Other names: tacrolimus modified release;Drug: Mycophenolate Mofetil<br>* Solution for infusion<br>* Other names: MMF;Drug: Corticosteroids<br>* IV bolus<br>* Other names: Methylprednisolone or equivalent;|
| Experimental: Dosing Regimen 2<br>Advagraf + MMF + Basiliximab + Corticosteroids (Bolus) | Drug: Advagraf<br>* Capsule<br>* Other names: tacrolimus modified release;Drug: Mycophenolate Mofetil<br>* Solution for infusion<br>* Other names: MMF;Drug: Basiliximab<br>* IV infusion<br>* Other names: Simulect;Drug: Corticosteroids<br>* IV bolus<br>* Other names: Methylprednisolone or equivalent;|
| Experimental: Dosing Regimen 3<br>Advagraf (5 days delay) + MMF + Basiliximab + Corticosteroids (Bolus) | Drug: Advagraf<br>* Capsule<br>* Other names: tacrolimus modified release;Drug: Mycophenolate Mofetil<br>* Solution for infusion<br>* Other names: MMF;Drug: Basiliximab<br>* IV infusion<br>* Other names: Simulect;Drug: Corticosteroids<br>* IV bolus<br>* Other names: Methylprednisolone or equivalent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glomerular filtration rate (GFR) at 24 Weeks after transplantation estimated using the MDRD4 formula |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of and time to first incidence of the composite event: graft loss (defined as re-transplantation or death) or biopsy confirmed acute rejection (BCAR) |  | 24 weeks | 
| GFR at 24 Weeks after transplantation measured by Iothalamate clearance |  | 24 weeks | 
| GFR at 24 Weeks after transplantation estimated using a Cystatin C based formula |  | 24 weeks | 
| Creatinine clearance at 24 Weeks after transplantation estimated using the Cockcroft and Gault formula |  | 24 weeks | 
| Incidence of and time to first incidence of acute rejection |  | 24 weeks | 
| Incidence of and time to first incidence of corticosteroid-resistant acute rejection |  | 24 weeks | 
| Overall frequency of acute rejection episodes |  | 24 weeks | 
| Incidence of and time to first incidence of biopsy confirmed acute rejection |  | 24 weeks | 
| Incidence of and time to first incidence of biopsy confirmed corticosteroid-resistant acute rejection |  | 24 weeks | 
| Overall frequency of biopsy confirmed acute rejection episodes |  | 24 weeks | 
| Severity of biopsy confirmed acute rejection episodes |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunosuppression, Liver, Transplant, Advagraf