To Evaluate the Efficacy and Safety of Tenofovir Alafenamide Conversion in Liver Transplant Patients

A Prospective, Single Center Study to Evaluate the Efficacy and Safety of Tenofovir Alafenamide Conversion in Liver Transplant Patients

This clinical trial aims to confirm the efficacy and safety of Vemlia® tablets (Tenofovir alafenamide) in liver transplant patients with hepatitis B, focusing on their effects on renal function.

HBV reactivation post-liver transplantation can result in a post-transplant mortality rate of up to 50% within two years, making prophylaxis critical. Currently, a combination therapy of HBIG and nucleotide analogues is commonly used. Among the nucleotide analogues (NA), entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are frequently used as first-line therapies. However, both ETV and TDF have nephrotoxicity, requiring caution in patients with chronic kidney disease. Specifically, 18% of liver transplant patients develop chronic kidney disease due to immunosuppressant use, making the appropriate use of antiviral drugs to preserve renal function crucial.

TAF has been reported through RCTs to be more effective than TDF in preserving renal function and bone density, while showing similar antiviral effects. However, these studies have been conducted exclusively on general chronic liver disease patients. Although multicenter studies have been reported for liver transplant patients, they were retrospective and involved a limited number of patients.

Therefore, the primary objective of this study is to assess the impact of converting to TAF on renal function preservation in liver transplant patients taking antivirals for HBV prophylaxis. The secondary objectives are to evaluate the antiviral effect on HBV, the impact on lipid profiles, and the effectiveness in preserving bone density.

Study Overview

• Status: Not yet recruiting
• Conditions: Renal Insufficiency; Liver Transplant; Hepatitis B Virus
• Intervention / Treatment: Drug: Tenofovir Alafenamide Citrate

Detailed Description

TAF has been reported through RCTs to be more effective than TDF in preserving renal function and bone density, while showing similar antiviral effects. However, these studies have been conducted exclusively on general chronic liver disease patients. Although multicenter studies have been reported for liver transplant patients, they were retrospective and involved a limited number of patients.

Therefore, the primary objective of this study is to assess the impact of converting to TAF on renal function preservation in liver transplant patients taking antivirals for HBV prophylaxis. The secondary objectives are to evaluate the antiviral effect on HBV, the impact on lipid profiles, and the effectiveness in preserving bone density.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jongman Kim, Ph, MD; Phone Number: +82-10-9365-0277; Email: jongman94.kim@samsung.com
• Study Contact Backup: Name: Jongman Kim, Ph, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged 19 years or older.

2. Patients who have maintained stable liver graft function for one year after liver transplantation due to HBV and meet the following conditions:

   ALT < 3 x ULN and AST < 3 x ULN

3. Patients taking antiviral therapy other than TAF for HBV prophylaxis.
4. Patients with a tacrolimus trough level maintained between 3-10 ng/mL.
5. Patients who have voluntarily decided to participate in the clinical trial after fully understanding the detailed explanation of the trial and have provided written consent.

Exclusion Criteria:

1. Patients who have undergone transplantation of organs other than the liver or re-transplantation.
2. Patients who have received BAL system treatment or auxiliary partial orthotopic liver transplantation (APOLT) before the transplantation.
3. Patients with concurrent viral infections (HCV, HIV).
4. Patients taking mTOR inhibitors (e.g., Everolimus (Certican), etc.).
5. Patients with eGFR <30 or those undergoing dialysis.
6. Pregnant or breastfeeding women.

7. Patients or their spouses/partners who do not agree to use medically acceptable and appropriate contraception methods* during the clinical trial period.

   • Appropriate contraception methods: hormonal contraception, intrauterine device (IUC or IUS), tubal ligation, tubal occlusion, hysterectomy, vasectomy, double barrier methods (combined use of male or female condoms with cervical caps, diaphragms, or contraceptive sponges), single barrier methods with spermicide.

     8 . Patients with a history of hypersensitivity to Tenofovir. 9 . Patients with genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

10. Patients who are deemed unsuitable for participation in the clinical trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Experimental(Tenofovir alafenamide); Tenofovir alafenamide is administered once every day with 25mg PO.	Drug: Tenofovir Alafenamide Citrate; Tenofovir alafenamide is administered once every day with 25mg PO for 48 weeks.; Other Names: Vemlia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of eGFR change	The amount of eGFR change at 12months after conversion compared to before TAF conversion	Through study completion, an average of 12months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of Creatinine change	Creatinine status by 12 months after conversion compared to before TAF conversion	an average of 12months
The amount of CKD stage change	CKD stage status by 12 months after conversion compared to before TAF conversion	an average of 12months
effectiveness	HBV recurrence rate	Through study completion, an average of 12months
BMD change	BMD status by 12 months after conversion compared to before TAF conversion	an average of 12months

Collaborators and Investigators

• Sponsor: Jongman Kim
• Investigators: Principal Investigator: Jongman Kim, Ph, MD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: September 9, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; Renal Insufficiency; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: 2024-07-122

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No