Tenofovir Alafenamide Switching Therapy in Kidney or Liver Transplant Recipients With Chronic HBV Infection

Safety Issues Clinical Trial

Official title:

A Prospective Cohort Study of Tenofovir Alafenamide Switching Therapy in Kidney or Liver Transplant Recipients With Chronic Hepatitis B Virus Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05410496
• Other study ID #: CF21160B
• Status: Recruiting
• Phase: Phase 4
• Start date: June 22, 2021
• Est. completion date: December 30, 2028

Study information

• Verified date: October 2023
• Source: Taichung Veterans General Hospital
• Contact: Teng-Yu Lee, MD, PhD
• Phone: +886423592525
• Email: tylee[@]vghtc.gov.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

tenofovir alafenamide (TAF) has been approved to be highly effective and safe in patients with chronic hepatitis B (CHB), therefore TAF may be a good option in kidney or liver transplant patients with chronic HBV infection. The aim of this prospective cohort study is to assess the safety, efficacy, and drug adherence improvement of TAF switching therapy in kidney or liver transplant patients with HBV infection.

Description:

Life-long nucleos(t)ide analogue (NA) therapy has been recommended in patients with chronic HBV infection after organ transplantation, therefore the safety of long-term NA therapy is particularly important in transplant patients. Entecavir, tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are recommended drugs for CHB patients in current guidelines because of their high potency in antiviral efficacy and low rate in virological resistance. However, the data of TAF therapy in transplant patients remain limited.

The potential nephrotoxicity and a decrease in bone mineral density (BMD) of TDF therapy have been reported in previous studies. TAF is a novel prodrug of tenofovir and is formulated to deliver the active metabolite to target cells more efficiently than TDF at a much lower dose, thereby reducing systemic exposure to tenofovir. In the randomized controlled trials of TDF versus TAF showed that virological and serological results were similar in both arms. However, patients in TAF arm had improved renal effects and BMD as compared to TDF. Improvement in renal function and BMD were also found in chronic hepatitis B patients who switched from TDF to TAF. Furthermore, in some retrospective studies, switching from entecavir to TAF may present a superior efficacy in HBV DNA suppression and HBsAg level reduction, and renal safety was comparable between the TAF switch group and the entecavir continuation group. Interestingly, switching from entecavir to TAF is associated with improvement of the medication adherence, which may be particularly important to patients under long-term NA therapy.

The clinical data of TAF therapy in transplant patients remain very limited, particularly in kidney transplant patients. With a high virological response rate and a low adverse effect (AE) rate in patients with CHB, TAF may be a good option for patients underwent liver or kidney transplantation.The aim of this study is to assess the safety, drug adherence, and efficacy of TAF switching therapy in kidney or liver or transplant patients with chronic HBV infection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 30, 2028
• Est. primary completion date: June 22, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. At least 20 years of age

2. Chronic HBV infection under NA therapy other than TAF

3. Underwent kidney and/ or liver transplantation

4. Without clinical or pathologic evidence of moderate or severe rejection

5. Patients who are indicated for TAF switching therapy, such as concerns in virological response, biochemical response, drug compliance, or safety issues to other NAs.

Exclusion Criteria:

1. End stage renal disease (eGFR < 15 mL/min/1.73m2)

2. Co-infected with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)

3. Any active malignancies

4. Pregnant or breast-feeding women

5. Known allergy to tenofovir-contained regimens

Related Conditions & MeSH terms

• Infections
• Safety Issues

Intervention

Drug:
• Tenofovir Alafenamide 25 MG
To assess the safety, efficacy, and drug adherence improvement of TAF switching therapy in kidney or liver transplant patients with HBV infection.

Locations

Country	Name	City	State
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung

Sponsors (2)

Lead Sponsor	Collaborator
Taichung Veterans General Hospital	Institute of Adherence to Medication

Country where clinical trial is conducted

Taiwan, 

References & Publications (14)

Buti M, Gane E, Seto WK, Chan HL, Chuang WL, Stepanova T, Hui AJ, Lim YS, Mehta R, Janssen HL, Acharya SK, Flaherty JF, Massetto B, Cathcart AL, Kim K, Gaggar A, Subramanian GM, McHutchison JG, Pan CQ, Brunetto M, Izumi N, Marcellin P; GS-US-320-0108 Inve — View Citation

Casado JL. Renal and Bone Toxicity with the Use of Tenofovir: Understanding at the End. AIDS Rev. 2016 Apr-Jun;18(2):59-68. — View Citation

Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang TY, Mehta R, Gane E, Flaherty JF, Massetto B, Gaggar A, Kitrinos KM, Lin L, Subramanian GM, McHutchison JG, Lim YS, Acharya SK, Agarwal K; GS-US-320-0110 Investig — View Citation

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017 Aug;67 — View Citation

Hagiwara S, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Komeda Y, Kudo M. Switching from entecavir to tenofovir alafenamide versus maintaining entecavir for chronic hepatitis B. J Med Virol. 2019 Oct;91(10):1804-1810. doi: 10.1002/jmv.25515. Epub 201 — View Citation

Kumada T, Toyoda H, Tada T, Yasuda S, Miyake N, Tanaka J. Comparison of the impact of tenofovir alafenamide and entecavir on declines of hepatitis B surface antigen levels. Eur J Gastroenterol Hepatol. 2021 Feb 1;32(2):255-260. doi: 10.1097/MEG.0000000000 — View Citation

Lampertico P, Buti M, Fung S, Ahn SH, Chuang WL, Tak WY, Ramji A, Chen CY, Tam E, Bae H, Ma X, Flaherty JF, Gaggar A, Lau A, Liu Y, Wu G, Suri V, Tan SK, Subramanian GM, Trinh H, Yoon SK, Agarwal K, Lim YS, Chan HLY. Switching from tenofovir disoproxil fu — View Citation

Li ZB, Li L, Niu XX, Chen SH, Fu YM, Wang CY, Liu Y, Shao Q, Chen G, Ji D. Switching from entecavir to tenofovir alafenamide for chronic hepatitis B patients with low-level viraemia. Liver Int. 2021 Jun;41(6):1254-1264. doi: 10.1111/liv.14786. Epub 2021 J — View Citation

Ogawa E, Nomura H, Nakamuta M, Furusyo N, Koyanagi T, Dohmen K, Ooho A, Satoh T, Kawano A, Kajiwara E, Takahashi K, Azuma K, Kato M, Shimoda S, Hayashi J; Kyushu University Liver Disease Study (KULDS) Group. Tenofovir alafenamide after switching from ente — View Citation

Rashidi-Alavijeh J, Straub K, Achterfeld A, Wedemeyer H, Willuweit K, Herzer K. Safety and efficacy of tenofovir alafenamide in liver transplant recipients: A single center experience. Transpl Infect Dis. 2021 Jun;23(3):e13522. doi: 10.1111/tid.13522. Epu — View Citation

Sripongpun P, Mannalithara A, Kwo PY, Kim WR. Potential Benefits of Switching Liver Transplant Recipients to Tenofovir Alafenamide Prophylaxis. Clin Gastroenterol Hepatol. 2020 Mar;18(3):747-749. doi: 10.1016/j.cgh.2019.05.057. Epub 2019 Jun 11. — View Citation

Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS Jr, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018 Apr;67(4):1560-1599. doi: 10.1002/hep — View Citation

Tsai HJ, Chuang YW, Lee SW, Wu CY, Yeh HZ, Lee TY. Using the chronic kidney disease guidelines to evaluate the renal safety of tenofovir disoproxil fumarate in hepatitis B patients. Aliment Pharmacol Ther. 2018 Jun;47(12):1673-1681. doi: 10.1111/apt.14682 — View Citation

Uchida Y, Nakao M, Tsuji S, Uemura H, Kouyama JI, Naiki K, Motoya D, Sugawara K, Nakayama N, Imai Y, Tomiya T, Mochida S. Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from e — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated glomerular filtration rate	0-120 ml/min/1.73m2 (higher scores mean a better outcome)	week 144
Primary	Bone mineral density	0-5 g/cm2; dual-energy X-ray absorptiometry (higher scores mean a better outcome)	week 144
Secondary	HBV viral load	0-8 log10 IU/mL; blood HBV DNA level (higher scores mean a worse outcome)	week 144
Secondary	Alanine aminotransferase	0-150000 IU/mL; blood ALT level (higher scores mean a worse outcome)	week 144
Secondary	Quantitative HBsAg	0-10000 IU/mL; blood qHBsAg level (higher scores mean a worse outcome)	week 144
Secondary	Liver fibrosis elastography	0-30 kPa; ultrasound elastography (higher scores mean a worse outcome)	week 144
Secondary	Drug adherence score	Score 1-8; Morisky Medication Adherence Scale-8 questionnaire	week 144 (higher scores mean a better outcome)