Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B

Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B: An Open Label, Randomized Controlled Trial

To compare the efficacy and renal safety of tenofovir alafenamide (TAF) versus entecavir (ETV) in the chronic hepatitis B patients.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis B; Viral Hepatitis
• Intervention / Treatment: Drug: Tenofovir alafenamide; Drug: Entecavir

Detailed Description

With high antiviral potency and low drug resistance rate, both ETV and tenofovir disoproxil fumarate (TDF) have been recommended as the first-line antiviral therapy for chronic hepatitis B (CHB). However, risk of renal dysfunction remains an issue in TDF long-term therapy. Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir and is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. Importantly, TAF had improved renal safety as compared to TDF. TAF has been approved for treating CHB since 2017; however, it is still unknown whether the efficacy and renal safety of TAF is compatible to those of ETV. The investigators aim to conduct an open label, randomized controlled trial comparing TAF with ETV for assessing their efficacy and renal safety in CHB patients. The eligible CHB patients are randomly assigned (1:1) to receive TAF or ETV. After allocation to TAF group or ETV group, study subjects will receive therapy for 3 years (144 weeks).

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Teng-Yu Lee, MD, PhD; Phone Number: 3301 886-4-23592525; Email: tylee@vghtc.gov.tw
• Study Contact Backup: Name: Hsin-Ju Tsai, MD; Phone Number: 3301 886-4-23592525; Email: a9194024@hotmail.com

Study Locations

• Taiwan
  • Taichung
    • Taichung, Taichung, Taiwan
      • Recruiting
      • Taichung Veterans General Hospital
      • Contact: Teng-Yu Lee, MD, PhD; Phone Number: 3301 886-4-23592525; Email: tylee@vghtc.gov.tw

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients more than 20 years old
2. Chronic hepatitis B patients
3. Patients who were indicated for hepatitis B virus antiviral therapy

Exclusion Criteria:

1. Decompensated liver disease (Child-Pugh B &C)
2. End stage renal disease (eGRF < 15 ml/min/1.73m2)
3. Prior use of nucleot(s)ide analogues for chronic hepatitis B
4. Prior use of interferon for chronic hepatitis B within six months
5. Known history of human immunodeficiency virus or hepatitis C virus co-infection
6. Concurrent other uncontrolled malignancy
7. Women in pregnancy or lactation
8. Cannot conform to the study protocol of this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tenofovir alafenamide group; Study subjects will receive tenofovir alafenamide 25 mg/tab once daily	Drug: Tenofovir alafenamide; Tenofovir alafenamide 25mg/tab once daily; Other Names: Vemlidy
Active Comparator: Entecavir group; Study subjects will receive entecavir 0.5 mg/tab once daily	Drug: Entecavir; Entecavir 0.5mg/tab once daily; Other Names: Baraclude

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HBV viral suppression	proportion of patients with hepatitis B virus(HBV) -DNA suppression	After 48-week therapy of Tenofovir alafenamide or entecavir
Renal safety: Change of estimated glomerular filtration rate	Change of estimated glomerular filtration rate	After 48-week therapy of Tenofovir alafenamide or entecavir

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal safety: Change of estimated glomerular filtration rate	Change of estimated glomerular filtration rate	After 144-week therapy of Tenofovir alafenamide or entecavir
HBV viral suppression	proportion of patients with hepatitis B virus(HBV) -DNA suppression	After 144-week therapy of Tenofovir alafenamide or entecavir
Normalization alanine aminotransferase (ALT)	proportion of patients with ALT normalization	After 144-week therapy of Tenofovir alafenamide or entecavir
HBsAg loss	proportion of patients with HBsAg loss	After 144-week therapy of Tenofovir alafenamide or entecavir
Bone mineral density	change of bone mineral density	After 144-week therapy of Tenofovir alafenamide or entecavir

Collaborators and Investigators

• Sponsor: Taichung Veterans General Hospital
• Investigators: Study Chair: Teng-Yu Lee, MD, PhD, Taichung Veterans General Hospital

Publications and helpful links

General Publications

• 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.29800. No abstract available.
• Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006 Oct;45(4):529-38. doi: 10.1016/j.jhep.2006.05.013. Epub 2006 Jun 23.
• Chen DS, Sung JL. Hepatitis B virus infection on Taiwan. N Engl J Med. 1977 Sep 22;297(12):668-9. doi: 10.1056/NEJM197709222971213. No abstract available.
• Ni YH, Chang MH, Wu JF, Hsu HY, Chen HL, Chen DS. Minimization of hepatitis B infection by a 25-year universal vaccination program. J Hepatol. 2012 Oct;57(4):730-5. doi: 10.1016/j.jhep.2012.05.021. Epub 2012 Jun 2.
• Chiang CJ, Yang YW, Chen JD, You SL, Yang HI, Lee MH, Lai MS, Chen CJ. Significant reduction in end-stage liver diseases burden through the national viral hepatitis therapy program in Taiwan. Hepatology. 2015 Apr;61(4):1154-62. doi: 10.1002/hep.27630. Epub 2015 Feb 10.
• Kang L, Pan J, Wu J, Hu J, Sun Q, Tang J. Anti-HBV Drugs: Progress, Unmet Needs, and New Hope. Viruses. 2015 Sep 15;7(9):4960-77. doi: 10.3390/v7092854.
• Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, Germanidis G, Lee SS, Flisiak R, Kaita K, Manns M, Kotzev I, Tchernev K, Buggisch P, Weilert F, Kurdas OO, Shiffman ML, Trinh H, Washington MK, Sorbel J, Anderson J, Snow-Lampart A, Mondou E, Quinn J, Rousseau F. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008 Dec 4;359(23):2442-55. doi: 10.1056/NEJMoa0802878.
• van Bommel F, Wunsche T, Mauss S, Reinke P, Bergk A, Schurmann D, Wiedenmann B, Berg T. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. Hepatology. 2004 Dec;40(6):1421-5. doi: 10.1002/hep.20464.
• 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. Epub 2018 Apr 25.
• Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013 Jun 4;158(11):825-30. doi: 10.7326/0003-4819-158-11-201306040-00007.
• 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(2):370-398. doi: 10.1016/j.jhep.2017.03.021. Epub 2017 Apr 18.
• 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 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):185-195. doi: 10.1016/S2468-1253(16)30024-3. Epub 2016 Sep 22.
• 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 Investigators. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 2016 Nov;1(3):196-206. doi: 10.1016/S2468-1253(16)30107-8. Epub 2016 Sep 22.
• Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L; BEHoLD AI463027 Study Group. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1011-20. doi: 10.1056/NEJMoa051287.

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 28, 2019
• First Submitted That Met QC Criteria: April 30, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hepatitis B; Entecavir; Tenofovir alafenamide; Viral Hepatitis
• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; 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 alafenamide; entecavir
• Other Study ID Numbers: CF18341A; 106DHA0500150 (Other Grant/Funding Number: Taichung Veterans General Hospital, Taiwan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes