Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B

NCT03933384 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: CF18341A106DHA0500150
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hepatitis B; Viral Hepatitis

Keywords

Hepatitis B; Viral Hepatitis; Tenofovir alafenamide; Entecavir

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Renal safety: Change of estimated glomerular filtration rate

  After 144-week therapy of Tenofovir alafenamide or entecavir

• HBV viral suppression

  After 144-week therapy of Tenofovir alafenamide or entecavir

• Normalization alanine aminotransferase (ALT)

  After 144-week therapy of Tenofovir alafenamide or entecavir

• HBsAg loss

  After 144-week therapy of Tenofovir alafenamide or entecavir

• Bone mineral density

  After 144-week therapy of Tenofovir alafenamide or entecavir

Study Arms (2)

Tenofovir alafenamide group

ACTIVE COMPARATOR

Study subjects will receive tenofovir alafenamide 25 mg/tab once daily

Drug: Tenofovir alafenamide

Entecavir group

ACTIVE COMPARATOR

Study subjects will receive entecavir 0.5 mg/tab once daily

Drug: Entecavir

Interventions

Tenofovir alafenamide DRUG

Tenofovir alafenamide 25mg/tab once daily

Also known as: Vemlidy

Tenofovir alafenamide group

Entecavir DRUG

Entecavir 0.5mg/tab once daily

Also known as: Baraclude

Entecavir group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients more than 20 years old
• Chronic hepatitis B patients
• Patients who were indicated for hepatitis B virus antiviral therapy

You may not qualify if:

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

Sponsors & Collaborators

• Taichung Veterans General Hospital: lead

Study Sites (1)

Taichung Veterans General Hospital

Taichung, Taichung, Taiwan

RECRUITING

Related Publications (14)

• 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.

  PMID: 16879891 BACKGROUND

• 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.

  PMID: 757978 BACKGROUND

• 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.

  PMID: 22668640 BACKGROUND

• 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.

  PMID: 25476749 BACKGROUND

• 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.

  PMID: 29405329 BACKGROUND

• 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.

  PMID: 28427875 BACKGROUND

• 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.

  PMID: 26389937 BACKGROUND

• 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.

  PMID: 16525138 BACKGROUND

• 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.

  PMID: 19052126 BACKGROUND

• 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.

  PMID: 15565615 BACKGROUND

• 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.

  PMID: 29696665 BACKGROUND

• 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.

  PMID: 23732715 BACKGROUND

• 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.

  PMID: 28404091 BACKGROUND

• 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.

  PMID: 28404092 BACKGROUND

MeSH Terms

Conditions

Hepatitis B

Interventions

tenofovir alafenamide; entecavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Teng-Yu Lee, MD, PhD

  Taichung Veterans General Hospital

  STUDY CHAIR

Central Study Contacts

Teng-Yu Lee, MD, PhD

CONTACT

886-4-23592525; tylee@vghtc.gov.tw

Hsin-Ju Tsai, MD

CONTACT

886-4-23592525; a9194024@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a study designed for non-inferior outcome comparisons for TAF and ETV. The eligible chronic hepatitis B patients are randomly assigned (1:1) to receive once-daily oral doses of TAF 25 mg or ETV 0.5mg.

Study Record Dates

• First Submitted: April 28, 2019
• First Posted: May 1, 2019
• Study Start: August 19, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)