E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
prophylaxis of liver allograft rejection in liver transplant recipients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066543 |
E.1.2 | Term | Acute allograft rejection |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate at Month 36 & 48 post-transplantation: - renal function; - composite efficacy endpoint of graft loss and death; - composite efficacy endpoint of treated biopsy proven acute rejection (BPAR), graft loss, or death; - rates of progression of HCV related allograft fibrosis.
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E.2.2 | Secondary objectives of the trial |
To evaluate at Months 36 and 48 post-transplantation: - treated BPAR; - Evolution of renal function/CNI-related side effects as defined by eGFR, hypertension, neurotoxicity, new onset diabetes; - Study-/ Study-Drug related findings as defined by premature discontinuation of study medication, premature discontinuation from the study, dose interruption, dose reduction of study medication, adverse events and serious adverse events, infections, major adverse cardiac events (MACE). - Evolution of HCV and HCV related fibrosis as defnied by HCV viral load (HCV-RNA levels) and progression of HCV fibrosis - rate of recurrence of hepatocellular carcinoma (HCC) in patients with a diagnosis of HCC prior to liver transplantation And fo describe the change in patterns of specific biomarkers for renal injury in the urine throughout the study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Ability and willingness to provide written informed consent before any assessment is performed; 2. Ability and willingness to adhere to study regimen; 3. Completed Month 24 visit of core study and continuously treated with assigned regimen.
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E.4 | Principal exclusion criteria |
1. Patients who have uncontrolled, severe hypercholesterolemia or hypertriglyceridemia; 2. Patients with platelet count <50,000/mm3; 3. Patients with an absolute neutrophil count of <1,000/mm³ or white blood cell count of <2,000/mm³; 4. Patients who have tested positive for human immunodeficiency virus (HIV); 5. Patients with clinically significant systemic infection requiring use of IV antibiotics; 6. Patients who are in a critical care setting requiring life support measures; 7. Use of prohibited medication; 8. Use of immunosuppressive agents or treatments not utilized in the protocol; 9. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes; 10. Pregnant or nursing (lactating) women; 11. Women of child-bearing potential not using highly effective methods of contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
Variable 1: Renal function measured by eGFR as calculated using the MDRD-4 formula at Month 36 post-transplantation; Variable 2: Composite efficacy endpoint of graft loss and death at Month 36 & 48; Variable 3: Composite efficacy endpoint of treated BPAR, graft loss, or death at Month 36; Variable 4: Clinically meaningful progression of HCV related allograft fibrosis at Month 36, defined as progression by at least 1 grade in the Ishak-Knodell score from extension baseline to Month 36.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Exploring biomarkers of renal function |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 47 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of study will be reached when the last patient has completed Visit 19 (Month 36). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |