Efficacy, Safety, Tolerability, Pharmacokinetics of Sotrastaurin-tacrolimus vs. Mycophenolic Acid-tacrolimus in de Novo Liver Transplant Patients

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of different doses of sotrastaurin when combined with tacrolimus for the prevention of acute rejection after de novo liver transplantation.

Official Title
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A 24-month Randomized Multicenter Study Evaluating Efficacy, Safety, Tolerability and Pharmacokinetics of Sotrastaurin and Tacrolimus vs. a Tacrolimus/Mycophenolate Mofetil-based Control Regimen in de Novo Liver Transplant Recipients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: MMF(1000mg bid) + tacrolimus + standard of care medications
* Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications
* Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications
* Drug: sotrastaurin (300 mg bid) + tacrolimus + standard of care medications


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Recipients of any race, 18 years or older Recipients of primary de novo orthotopic liver transplant from a deceased donor Recipients of a kidney with a cold ischemia time < 30 hours HCV-negative recipients Exclusion criteria: Prior organ/cellular transplant or multiple organ transplant MELD-score > 35 HCC > Milan criteria Donor age < 12 years Cold ischemia > 15 hours Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) or drugs with QT-prolonging properties 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>MMF(1000mg bid) + tacrolimus + standard of care medications | Drug: MMF(1000mg bid) + tacrolimus + standard of care medications<br>* MMF(1000mg bid) + tacrolimus + standard of care medications<br>|
| Experimental: Arm 2<br>sotrastaurin (200mg bid) + tacrolimus + standard of care medications | Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications<br>* sotrastaurin (200mg bid) + tacrolimus + standard of care medications<br>|
| Experimental: Arm 3<br>sotrastaurin (200mg bid) + tacrolimus + standard of care medications | Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications<br>* sotrastaurin (200mg bid) + tacrolimus + standard of care medications<br>|
| Experimental: Arm 4<br>sotrastaurin (300 mg bid) + tacrolimus + standard of care medications | Drug: sotrastaurin (300 mg bid) + tacrolimus + standard of care medications<br>* sotrastaurin (300 mg bid) + tacrolimus + standard of care medications<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of primary efficacy failure defined as composite efficacy endpoint (treated BPAR of Banff grade ≥ 1, graft loss, or death) in the different treatment arms. |  | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockcroft-Gault formula; serum creatinine). |  | Months 3, 6, 12, and 24 | 
| Occurrence of primary efficacy failure defined as composite efficacy endpoint (treated BPAR of Banff grade ≥ 1, graft loss, or death) in the different treatment arms. |  | Months 12, 24 | 
| Occurrence of rejection requiring T-cell depleting antibody, occurrence of treated biopsy-proven acute rejections of Banff grade ≥ 1 that is steroid-resistant |  | Months 6, 12, 24 | 
| Safety and tolerability ((serious) adverse events (specifically: gastrointestinal AEs and cardiac AEs, serious infections), laboratory abnormalities, vital signs, electrocardiograms, physical examination). |  | Months 3, 6, 12, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplantation, HCV-negative recipient, deceased donor, sotrastaurin, oran transplantation, tacrolimus