E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10024716 |
E.1.2 | Term | Liver transplantation |
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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 |
The primary objectives to be evaluated at Months 36 and 48* post-transplantation include: ? renal function; ? the composite efficacy endpoint of graft loss or death; ? the composite efficacy endpoint of treated biopsy proven acute rejection (BPAR), graft loss, or death; ? The rate of progression of HCV related allograft fibrosis. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives ? To evaluate the efficacy endpoint of treated BPAR at Months 36 and 48 posttransplantation ? Evolution of renal function and CNI-related side effects at Months 36 and 48 posttransplantation: ? To evaluate renal function by eGFR (MDRD-4 formula) and calculated creatinine clearance (Cockcroft-Gault formula); ? To evaluate the prevalence of CNI-related side effects such as hypertension, neurotoxicity, new-onset diabetes mellitus (NODM); ? Study-/ Study-Drug related findings at Months 36 and 48 post-transplantation: ? To evaluate the premature discontinuation of study medication, and discontinuation from the study; ? To evaluate the incidence of dose interruption and dose reduction of study medication; ? To evaluate the incidence of adverse events (AEs) and serious adverse events (SAEs); ? To evaluate the incidence of infections; ? To evaluate the incidence of major adverse cardiac events (MACE). ? PLS SEE PROTOCOL |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Ability and willingness to provide written informed consent before any extension specific assessment is performed. 2. Ability and willingness to adhere to study regimen. 3. Completed Month 24 visit of core study and continuously being treated with assigned regimen. |
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E.4 | Principal exclusion criteria |
Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Patients who have uncontrolled, severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) at the evaluation before enrolment into the extension (to be confirmed at Month 24). 2. Patients with platelet count <50,000/mm3 at the evaluation before enrolment into the extension (to be confirmed at Month 24). 3. Patients with an absolute neutrophil count of <1,000/mm? or white blood cell count of <2,000/mm? at the evaluation before enrolment into the extension (to be confirmed at Month 24) Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Patients who have uncontrolled, severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) at the evaluation before enrolment into the extension (to be confirmed at Month 24). 2. Patients with platelet count <50,000/mm3 at the evaluation before enrolment into the extension (to be confirmed at Month 24). 3. Patients with an absolute neutrophil count of <1,000/mm? or white blood cell count of <2,000/mm? at the evaluation before enrolment into the extension (to be confirmed at Month 24) 4. Patients who have tested positive for human immunodeficiency virus (HIV). 5. Patients with clinically significant systemic infection requiring active use of IV antibiotics at Month 24. 6. Patients who are in a critical care setting at Month 24 requiring life support measures such as mechanical ventilation, dialysis, requirement of vasopressor agents. 7. Use of medication that is prohibited by the study protocol at Month 24. 8. Use of immunosuppressive agents or treatments at Month 24 that are 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, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive BHCG laboratory test (> 5 mIU/mL) 11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS a. their career, lifestyle, or sexual orientation precludes intercourse with a male partner, or b. their partners have been sterilized by vasectomy or other means, or c. they are using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices (IUDs); not highly effective are e.g. single-barrier methods, combination of female barrier method with spermicidal gel, periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal. Reliable contraception should be maintained throughout the study and for 8 weeks after study drug discontinuation. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible patients. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objectives to be evaluated at Months 36 and 48* post-transplantation include: ? renal function; ? the composite efficacy endpoint of graft loss or death; ? the composite efficacy endpoint of treated biopsy proven acute rejection (BPAR), graft loss, or death; ? The rate of progression of HCV related allograft fibrosis. |
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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 | No |
E.6.13 | Others | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
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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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 | 11 |
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 |