Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B

Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03933384
• Other study ID #: CF18341A
• Secondary ID: 106DHA0500150
• Status: Recruiting
• Phase: Phase 4
• Start date: August 19, 2019
• Est. completion date: December 31, 2033

Study information

• Verified date: October 2023
• Source: Taichung Veterans General Hospital
• Contact: Teng-Yu Lee, MD, PhD
• Phone: 886-4-23592525
• Email: tylee[@]vghtc.gov.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: December 31, 2033
• Est. primary completion date: December 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Viral Hepatitis

Intervention

Drug:
• Tenofovir alafenamide
Tenofovir alafenamide 25mg/tab once daily
• Entecavir
Entecavir 0.5mg/tab once daily

Locations

Country	Name	City	State
Taiwan	Taichung Veterans General Hospital	Taichung

Sponsors (1)

Lead Sponsor	Collaborator
Taichung Veterans General Hospital

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

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

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. — View Citation

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. Epu — 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

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. — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

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 pr — 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

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV viral suppression	proportion of patients with hepatitis B virus(HBV) -DNA suppression	After 48-week therapy of Tenofovir alafenamide or entecavir
Primary	Renal safety: Change of estimated glomerular filtration rate	Change of estimated glomerular filtration rate	After 48-week therapy of Tenofovir alafenamide or entecavir
Secondary	Normalization alanine aminotransferase (ALT)	proportion of patients with ALT normalization	After 48-week therapy of Tenofovir alafenamide or entecavir
Secondary	HBsAg loss	proportion of patients with HBsAg loss	After 48-week therapy of Tenofovir alafenamide or entecavir
Secondary	HBeAg loss	proportion of patients with HBeAg loss	After 48-week therapy of Tenofovir alafenamide or entecavir
Secondary	Bone mineral density	change of bone mineral density	After 48-week therapy of Tenofovir alafenamide or entecavir