Evaluate the Efficacy and Safety of the ADVAGRAF® (STABLE)

February 17, 2021 updated by: Linical Korea

A Phase IV, Single Center, Open-label, Single-arm Study to Evaluate the Efficacy and Safety of the Conversion to Tacrolimus Modified Release, ADVAGRAF® After 12 Month Treatment With a Tacrolimus Stably in Liver Transplant Recipients.

The primary objective of this study is to evaluate the efficacy of 6-month treatment with Advagraf® converted from 12-month treatment with tacrolimus in stable liver transplant recipients.

The secondary objective of this study is to evaluate severity of acute rejection confirmed by biopsy in 24 weeks, incidence of chronic rejection, patient and graft survival rates in 24 weeks, incidence of adverse events, blood pressure, tacrolimus trough level, drug compliance, and adherence.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is single-center, single-group, open-label study, phase 4 IIT. The Subject is transplantated liver at a minimum of 12 month of screening and at least 12 month Treatment with a Tacrolimus stably And start screening after obtain consent to participate in clinical trials, if appropriate in the selection criteria do not apply to the exclusion criteria are enrolled in clinical trials.

Administration method is following : The total daily dose of -1 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 for 24 weeks, starting from Day 0.

Researchers must check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5~10ng/ml of study treatment.

Duration of treatment : The investigational product will be administered for 24 weeks.

Tacrorimus blood level is 3-10 ng/ml for 6 months prior to screening and during the maintenance therapy. It is recommended to check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5~10ng/ml of study treatment. (The lowest blood levels shall be adjusted at the discretion of the researchers, taking a blood sample is carried out in the morning before have of Investigational Product)

Subjects, who participated in this clinical trial, are scheduled up to 5 times, and it will be proceed for 24 weeks. (screening and baseline, 3 weeks, 12 weeks, 24 weeks) admitted for 24 weeks including a screening visit.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Aged between 19 and 80 years old
  2. Those who were transplantated liver at a minimum of 12 month of screening and after 12 month Treatment with a Tacrolimus stably.(Brain dead transplantation or biological transplant no values)
  3. tacrolimus blood everage level is 3-10 ng/ml for at least 6 months prior to screening.
  4. Female subjects of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment and at the end of study and must agree to practice effective birth control during the study.
  5. Subjects are stable clinically in the opinion of the investigator.
  6. Subjects 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:

  1. 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.
  2. Acute rejection confirmed by histologic response or the patient had chronic rejection
  3. Subjects diagnosed new malignant tumor before the pre-screening within five years , with the exception of basalioma or squamous cell carcinoma or carcinoma in situ of the skin that has been treated successfully.
  4. Subjects allergic to tacrolimus or investigational product.
  5. Subjects are unstable clinically state in the opinion of the investigator.
  6. Subjects with any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator.
  7. Subjects 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.
  8. Subjects taking forbidden concomitant medications or within 28 days prior to enroll.
  9. Subjects who are pregnant or breast-feeding mother.
  10. Subjects unlikely to comply with the visits scheduled in the protocol.
  11. Subjects with renal dysfunction on the investigator's point of view or serum creatinine > 1.6mg/dL or GFR(MDRD)<30mL/min in the baseline.
  12. Hepatic dysfunction: rising more than double the normal range of SGPT/ALT and/or SGOT/AST and/or bilirubin, hepatic cirrhosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: tacrolimus
conversion to Advagraf
Drug: Advagraf

Researchers must check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5~10ng/ml of study treatment. Duration of treatment The investigational product will be administered for 24 weeks. (The lowest blood levels shall be adjusted at the discretion of the researchers, taking a blood sample is carried out in the morning before administrated of Investigational Product)

Tacrolimus blood level is 3-10 ng/ml for 6 months prior to screening and during the maintenance therapy.

( ① -1day to enrollment : swich to the day before ADVAGRAF®, ② 0day to enrollment : the day swich to ADVAGRAF® )

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 of acute rejection confirmed by biopsy in 24 weeks after conversion
Time Frame: within 24 weeks
  • Incidence of acute rejection (%) = no. of subjects who had acute rejection at least once / no. of all the subjects in the relevant analysis set * 100
  • Only acute rejection confirmed by biopsy will be recognized.
  • In addition, concomitant immunosuppressants other than tacrolimus will be divided into sub-groups (by type and dosage/administration), and point estimation and calculation of 95% two-sided confidence interval will be conducted for incidence of acute rejection.
within 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of acute rejection confirmed by biopsy in 24 weeks after conversion
Time Frame: within 24 weeks
* For the subjects who developed acute rejection at least once, severity of acute rejection is defined as the highest severity.
within 24 weeks
Incidence of chronic rejection
Time Frame: within 24 weeks
* Chronic rejection will be confirmed by biopsy.
within 24 weeks
Patient and graft survival rates in 24 weeks after conversion
Time Frame: within 24 weeks
within 24 weeks
Time from conversion to onset of acute rejection
Time Frame: within 24 weeks
within 24 weeks
Tacrolimus trough level at each visit
Time Frame: within 24 weeks
within 24 weeks
Incidence of adverse events
Time Frame: within 24 weeks
within 24 weeks
Tacrolimus compliance
Time Frame: within 24 weeks
Evaluation of adherence through a subject questionnaire
within 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Linical Korea

Collaborators

Asan Medical Center

Investigators

  • Principal Investigator: Ki Won Song, doctral, Asan Medical Center, Hepatobiliary, Liver Transplantion Surgery center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Actual)

April 1, 2020

Study Completion (Actual)

April 1, 2020

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

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STABLE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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