- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03933384
Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B
October 7, 2023 updated by: Teng-Yu Lee, Taichung Veterans General Hospital
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
Intervention / Treatment
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)
420
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
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
-
-
-
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
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Patients more than 20 years old
- Chronic hepatitis B patients
- Patients who were indicated for hepatitis B virus antiviral therapy
Exclusion Criteria:
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Tenofovir alafenamide group
Study subjects will receive tenofovir alafenamide 25 mg/tab once daily for 3 years (144 weeks).
|
Tenofovir alafenamide 25mg/tab once daily
Other Names:
|
Active Comparator: Entecavir group
Study subjects will receive entecavir 0.5 mg/tab once daily for 3 years (144 weeks).
|
Entecavir 0.5mg/tab once daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HBV viral suppression
Time Frame: After 48-week therapy of Tenofovir alafenamide or entecavir
|
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
Time Frame: After 48-week therapy of Tenofovir alafenamide or entecavir
|
Change of estimated glomerular filtration rate
|
After 48-week therapy of Tenofovir alafenamide or entecavir
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Normalization alanine aminotransferase (ALT)
Time Frame: After 48-week therapy of Tenofovir alafenamide or entecavir
|
proportion of patients with ALT normalization
|
After 48-week therapy of Tenofovir alafenamide or entecavir
|
HBsAg loss
Time Frame: After 48-week therapy of Tenofovir alafenamide or entecavir
|
proportion of patients with HBsAg loss
|
After 48-week therapy of Tenofovir alafenamide or entecavir
|
HBeAg loss
Time Frame: After 48-week therapy of Tenofovir alafenamide or entecavir
|
proportion of patients with HBeAg loss
|
After 48-week therapy of Tenofovir alafenamide or entecavir
|
Bone mineral density
Time Frame: After 48-week therapy of Tenofovir alafenamide or entecavir
|
change of bone mineral density
|
After 48-week therapy of Tenofovir alafenamide or entecavir
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Teng-Yu Lee, MD, PhD, Taichung Veterans General Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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.
- 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(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. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
- 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. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
- 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.
- 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. Erratum In: N Engl J Med. 2006 Apr 27;354(17):1863.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 19, 2019
Primary Completion (Estimated)
December 31, 2028
Study Completion (Estimated)
December 31, 2033
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)
October 10, 2023
Last Update Submitted That Met QC Criteria
October 7, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Disease Attributes
- Liver Diseases
- Hepatitis, Viral, Human
- Hepadnaviridae Infections
- DNA Virus Infections
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Chronic Disease
- Hepatitis B
- Hepatitis
- Hepatitis A
- Hepatitis B, Chronic
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Tenofovir
- 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
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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