E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
maintenance of liver transplant |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to determine whether initiation of CerticanTM together with reduction or discontinuation of CNI in maintenance liver transplant patients with CNI-related renal impairment will significantly improve the renal function. This will be evaluated by comparing change in renal function assessed by calculated Glomerular Filtration Rate (cGFR) from Baseline to Month 6 after randomization between the study group and the control group with continuation of CNI-based regimen. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the efficacy and safety of conversion from standard immunosuppression to CerticanTM-based immunosuppression. This will be evaluated by comparisons between the 2 groups at 6 months after randomization for: • Incidence of efficacy failure (Biopsy Proven Acute Rejection (BPAR), graft loss or death) • Incidence of treated BPAR • Patient and graft survival • Safety parameters including : hypertension, diabetes mellitus, hyperlipidemia, anemia, infections and malignancies • Incidence of discontinuation of study medication • Incidence of premature study withdrawal • Incidence of Serious Adverse Event The HCV replication in HCV positive patients will also be explored.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
The investigator must ensure that each patient meet all the following inclusion criteria at screening visit: • Male or female 18 - 70 years old • Patient who has undergone a primary liver transplantation 12 to 60 months ago from a cadaveric or a living donor • Patient with a cGFR ≤ 60 and greater or equal than 20mL/min • Patient receiving Prograf® with C0-h level greater than or equal to 3 and ≤ 8 ng/mL, or Neoral® with C0-h level greater or equal to 50 and ≤ to 150 ng/mL with or without any of the following (MPA or AZA or steroids) • Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 6 months • Patient in whom an allograft biopsy will not be contraindicated • Female capable of becoming pregnant must have a negative pregnancy test prior to randomization and are required to practice a medically approved method of birth control for the duration of the study
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E.4 | Principal exclusion criteria |
The patient meeting any of the following criteria at screening visit will be excluded from the study participation: • Recipient of multiple solid organ transplants • Patient on dialysis • Patient with an identifiable cause of renal dysfunction other than CNI toxicity • Patient with proteinuria greater than or equal to 1.0 g/24h • Patient with any acute rejection within 6 months prior to randomization • Patient with platelet count of ≤ 50,000/mm³ or white blood cell count of ≤ 2,000/mm³ or hemoglobin value ≤ 8 g/dL • Patient with graft dysfunction associated with bilirubin > 34 mmol/L, or albumin < 35 g/L or prothrombin time > 1.3 INR • HCV positive patient who needs an active anti-viral treatment • HIV positive patient • Patient who is breast feeding • Patient with a current severe systemic infection • Patient who has received an unlicensed drug or therapy within one month prior to study entry • Presence of any hypersensitivity to drugs similar to CerticanTM(e.g. macrolides) • Use of any other immunosuppressive drugs than Prograf®/Neoral®, steroids, azathioprine and MPA
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E.5 End points |
E.5.1 | Primary end point(s) |
Demonstration of whether initiation of Certican together with reduction or discontinuation of calcineurin inhibitors (Neoral or Prograf), will improve the renal function significantly more than in the control group. The change in renal function is assessed by calculating the glomerular filtration rate (GFR) from baseline to month 6, after randomisation between the study group and the control group. The targeted population is maintenance liver transplant patients with calcineurin inhibitor's-related renal impairment. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.1 | Randomised | Information not present in EudraCT |
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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6 months on trial then a follow up status update, after one year |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |