Tacrolimus for Liver transplant rejection (prophylaxis)

Inclusion criteria

• {"criterion_text":"- Signed and dated written informed consent\n- Adult (≥18 years old) male or female\n- Recipient of a whole liver transplant from a deceased donor or a split liver transplant from a deceased or living donor\n- ABO blood type compatible with the organ donor\n- Able to swallow an oral formulation of tacrolimus in tablet or capsule form"}

Exclusion criteria

• {"criterion_text":"- Multi-organ transplantation\n- Ongoing, planned or foreseeable use of cyclosporine or any tacrolimus preparation other than Envarsus® or Advagraf® (except for immediate-release formulations administered before randomisation)\n- Any prolonged-release tacrolimus treatment prior to randomisation\n- Pregnant or nursing (lactating) female, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test\n- Female of child-bearing potential, defined as physiologically capable of becoming pregnant, unless using a reliable method* of contraception\n- Participation in another interventional clinical trial during the time period from randomisation to study end, if the trial is testing an IMP (AMG study**) or if the intervention and/or follow-up requirements of the trial impede or interfere with either the objectives of EnGraft or the treatment / follow-up requirements of EnGraft\n- Any condition or factor which, in the judgement of the investigator, would place the subject at undue risk, invalidate communication with the investigator or study team, or hamper compliance with the trial protocol or follow-up schedule\n- Inability to freely give informed consent (e.g. individuals under legal guardianship)\n- Any previous organ allograft transplantation\n- Biopsy-proven acute rejection that is ongoing at the time of randomisation\n- Occurrence of post-transplant thrombosis, occlusion or stent placement in any major hepatic arteries, hepatic veins, portal vein or inferior vena cava\n- History of extra-hepatic malignancy that could not be curatively treated\n- Hepatocellular carcinoma with extra-hepatic spread or macrovascular invasion\n- Uncontrolled systemic infection\n- Requirement of life support measures such as ventilation or vasopressor agents (>20 μg/kg BW/h) at the time of randomisation\n- Known contraindication or hypersensitivity to tacrolimus, and/or to any of the excipients listed in section 6.1 of the Summary of Product Characteristics (SmPC) of both Envarsus® and Advagraf®, and/or to any other macrolides"}

Primary endpoints

• {"endpoint_text":"- Dose-normalised trough level (C/D ratio) measured at 12 weeks","definition_or_measurement_approach":"C/D ratio = concentration/dose ratio used as an estimate of tacrolimus bioavailability; measured trough level at 12 weeks."}

Secondary endpoints

• {"endpoint_text":"- Number of IMP dose adjustments until 12 weeks\n- Time to reach the first defined range in target trough level\n- Number of measurements above and below the first defined range in target trough level\n- Dose-normalised trough level (C/D ratio) measured at 1, 2 and 3 years\n- Mean tacrolimus trough level and inter-patient variability (range) of tacrolimus trough levels at 1, 2, 4 and 12 weeks\n- Inter-patient variability (range) of tacrolimus total daily dose until 12 weeks\n- Proportion of patients with trough levels lower, within, or higher than the standard reference range at 1, 2, 4 and 12 weeks\n- Incidence and severity (BANFF criteria) of clinically-confirmed BPAR2 at 12 weeks and 1, 2, 3 years\n- Incidence of graft failure (defined as necessity for re-transplantation) at 12 weeks and 1, 2, 3 years\n- Incidence of death (for any reason) at 12 weeks and 1, 2, 3 years\n- Treatment failure rate (composite endpoint of BPAR, graft failure or death) at 12 weeks and 1, 2, 3 years\n- Time to treatment failure (composite endpoint of BPAR, graft failure3 or death) after randomisation\n- Incidence of acute rejections requiring treatment at 12 weeks\n- Incidence of multiple rejection episodes at 12 weeks\n- Laboratory measures at 12 weeks and 1, 2, 3 years: liver function, metabolic profile, renal function\n- Malignancies at 1, 2 and 3 years\n- Infections (HCV, HBV, CMV, EBV) at 1, 2 and 3 years\n- Degree of liver fibrosis (fibroscan4 or biopsy) at 12 weeks and 1, 2, 3 years\n- Incidence, type, severity, seriousness and causality of adverse events (AEs)\n- Change vs. baseline in vital signs (heart rate, blood pressure) and body weight\n- Incidence of de novo occurrence of tremor or vision impairments\n- Incidence of post-transplant diabetes mellitus and post-transplant hyperglycaemia at 12 weeks and 1, 2, 3 years\n- Dose-normalised trough level (C/D ratio) 12 weeks after transplantation\n- Number and doses of immunosuppressive medications (incl. other tacrolimus formulations) at 12 weeks and after 12 weeks (if applicable)\n- Recurrence of primary hepatic disease\n- Incidence of DSA up to 12 weeks and at 1, 2 and 3 years (optional)\n- Continuation rate at 12 weeks\n- Incidence and time to study treatment discontinuation\n- Incidence, time to and reason for patient withdrawal from study","definition_or_measurement_approach":"Endpoints are measured at the timepoints stated in each endpoint (e.g., counts or incidences up to 12 weeks and at 1, 2, 3 years; trough levels and C/D ratio measured from blood samples at specified weeks)."}

Germany

Earliest CTIS Part Ii Submission Date

12-09-2024

Latest Decision Or Authorization Date

31-10-2024

Processing Time Days

49

Number Of Sites

15

Number Of Participants

268

Primary sponsor

Full Name

Universitaetsklinikum Regensburg AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Contract research organisations

Name

Excelya Germany GmbH

Responsibilities

sponsorDuties code 10; contact@excelya.com

Third parties

• {"country":"Germany","full_name":"Excelya Germany GmbH","duties_or_roles":"sponsorDuties code 10; contact@excelya.com","organisation_type":"Pharmaceutical company"}