To Evaluate the Efficacy and Safety of ADVAGRAF® After Treatment With a Tacrolimus in New Liver Transplant Recipients (Assign)

A Single Center, Single Arm, Open-label Study to Evaluate the Efficacy and Safety of Tacrolimus Modified Release, ADVAGRAF® After Treatment With a Tacrolimus in New Liver Transplant Recipients

This study's objective is to evaluate the incidence rate of acute rejection reactions after 24 weeks treatment with ADVAGRAF® following 3 months treatment with tacrolimus in new liver transplant recipients.

Treatment conversion will take place from twice daily tacrolimus to once daily tacrolimus (ADVAGRAF) 3 months after transplant in new liver transplant recipients.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation
• Intervention / Treatment: Drug: ADVAGRAF®

Detailed Description

This is single center,open-label study with ADVAGRAF® Primary endpoint is Incidence rate of biopsy confirmed acute rejection reactions within 24 weeks following conversion+ Incidence rate of acute rejection reactions (%) = number of subjects with at least one acute rejection reaction 1)/total number of subjects in the relevant analysis set * 100 Only those acute rejection reactions confirmed by biopsy will be acceptable as acute rejection reactions.

Administration method is following The total daily dose of tacrolimus will be converted to 1:1 (mg:mg) and the total daily dose of ADVAGRAF® will be administered only once daily in the morning, starting from Day 1 (at least one hour before breakfast or 2 to 3 hours after breakfast).

• Dose adjustment after conversion On Day 1, the total dose will be converted to 1:1. It is recommended to check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5~8ng/ml for 0 to 3 months and then at 5ng/ml or below for 3 to 6 months of study treatment.
• Duration of treatment The investigational product will be administered for 24 weeks.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• When the Subjects agree informed consent form, Subject should be More than 20 years of age

  • Those who are transplanated liver at a minimum of 10 weeks or Maximum of 14 weeks of baseline

    • Average of tacrorimus trough level is 3-10 ng/mL from transplanted date to before baseline.

      • Female subjects of child bearing potential must have a negative urine or serum pregnancy test prior to enrolment and at the end of study and must agree to practice effective birth control during the study.(The oral contraceptive pill is not allowed to take a female subject) ⑤Subjects are stable clinically in the opinion of the investigator. ⑥Subjects capable of understanding the purpose and risks of the study, having been fully informed and has given written informed consent to participate in the study

Exclusion Criteria:

• Subjects having previously received an organ transplant excluding liver transplant. Or Subjects receiving an auxiliary graft or in whom a bio-artificial liver(cell system) has been used.

  • Acute rejection from transplanted date to before baseline

    • Subjects diagnosed new malignant tumor after liver transplantation, with the exception of basalioma or squamous cell carcinoma of the skin that has been treated successfully.

      • Subjects allergic to tacrolimus or investigational product.

        • Subjects are unstable clinically state in the opinion of the investigator.

          • Subjects with any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator.

            ⑦Subjects participating or having participated in another clinical trial and/or those taking or having taken an investigational / non-registered drug in the past 28 days.

            ⑧Subjects taking forbidden concomitant medications or within 28 days prior to enroll.

            • Subjects who are pregnant or breast-feeding mother.

              ⑩Subjects known to be HIV positive.

              ⑪Subjects unlikely to comply with the visits scheduled in the protocol.

              ⑫Subjects with renal dysfunction on the investigator's point of view or serum creatinine > 1.6mg/dL or GFR(MDRD)<30mL/min in the baseline.

              ⑬Hepatic dysfunction: rising more than triple the normal range of SGPT/ALT and/or SGOT/AST and/or bilirubin, hepatic cirrhosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ADVAGRAF®; One arm: Treatment conversion will take place from twice daily tacrolimus to once daily tacrolimus (ADVAGRAF) 3 months after transplant in new liver transplant recipients.

Drug: ADVAGRAF®; Administration method The total daily dose of tacrolimus will be converted to 1:1 (mg:mg) and the total daily dose of ADVAGRAF® will be administered only once daily in the morning, starting from Day 1 (at least one hour before breakfast or 2 to 3 hours after breakfast).; Dose adjustment after conversion On Day 1, the total dose will be converted to 1:1. It is recommended to check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5~8ng/ml for 0 to 3 months and then at 5ng/ml or below for 3 to 6 months of study treatment.; Duration of treatment The investigational product will be administered for 24 weeks.; Other Names: tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence rate of biopsy confirmed acute rejection	Incidence rate of acute rejection reactions (%) = number of subjects with at least one acute rejection reaction 1)/total number of subjects in the relevant analysis set * 100	24 weeks within

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of biopsy confirmed acute rejection	Severity of acute rejection reactions is defined as the highest severity in a subject who had at least one acute rejection reaction.	within 24 weeks
Survival rates of subjects and transplanted organs	The survival rate of transplant organs is determined by the loss of transplant organs in the 24th week. Transplant organ loss is defined as re-transplant surgery or death. The date of the transplant's disappearance is the first time one of these events has occurred.	at 24 weeks
compliance	The dosage compliance level is checked by the questionnaire at each visit based on the total amount of the IPs that should have been taken.	at 24 weeks

Collaborators and Investigators

• Sponsor: Linical Korea
• Collaborators: National Cancer Center, Korea; Astellas Pharma Korea, Inc.
• Investigators: Principal Investigator: seoung hoon Kim, doctoral, National Cancer Center, Korea

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): December 14, 2017
• Study Completion (Actual): December 14, 2017

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: liver transplantation; tacrolimus; ADVAGRAF®
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: Assign