Effectiveness of TAF in Reducing Clinical Events in CHB Patients Beyond Treatment Indications by Current Guidelines
NCT ID: NCT03753074
Last Updated: 2024-12-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE4
780 participants
INTERVENTIONAL
2019-02-18
2031-12-31
Brief Summary
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Detailed Description
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Study procedure: 780 subjects will be randomized in a 1:1 ratio (A:B) either to receive TAF 25 mg QD or to receive best supportive care after stratification according to the HBeAg status.
The study duration is 12 years. During treatment period, among treatment arm B, subjects who are indicated for antiviral treatment will be treated with TAF as follows:
1. Based on the AASLD 2018 Guidelines of CHB (ALT 70≥ for male, 50≥ for female)
2. 40≤ALT levels\<70 IU/L (males) or 40≤ ALT levels\<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.
3. If they were clinically judged to have cirrhosis by investigators and confirmed with Fibroscan (≥ 12.0 kPa).
* Treatment Arm A: 390 subjects administered TAF 25 mg once daily
* Treatment Arm B: 390 subjects received best supportive care
The primary analysis will occur at Year 4 with the primary endpoint being occurrence of composite events during follow-up observation
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Treatment Arm A (TAF)
390 subjects administered Tenofovir Alafenamide 25 mg once daily
Tenofovir Alafenamide
Tenofovir Alafenamide 25mg, Tablet, Oral, Daily
Treatment Arm B (Best supportive care)
390 subjects received best supportive care
During treatment period, among treatment arm B, subjects who are indicated for antiviral treatment will be treated with TAF as follows:
1. Based on the AASLD 2018 Guidelines of CHB (ALT 70≥ for male, 50≥ for female)
2. 40≤ALT levels\<70 IU/L (males) or 40≤ ALT levels\<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.
3. If they were clinically judged to have cirrhosis by investigators and confirmed with Fibroscan (≥ 12.0 kPa).
No interventions assigned to this group
Interventions
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Tenofovir Alafenamide
Tenofovir Alafenamide 25mg, Tablet, Oral, Daily
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Male or female, 40 to 80 years of age
3. Positive for HBsAg or HBV DNA for at least 6 months or more
4. HBeAg positive or negative
5. No evidence of liver cirrhosis (platelet count ≥100,000/mm3)
6. serum HBV DNA ≥ 4 log10 IU/mL and ≤ 8 log10 IU/mL
7. Serum ALT level \<70 if male, \<50 if female
8. Estimated creatinine clearance ≥ 30 ml/min based on serum creatinine as measured at the screening evaluation
9. Patient is willing and able to comply with all study requirements
Exclusion Criteria
2. Abusing alcohol (more than 60 g/day) or illicit drugs
3. Patients with history of hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)
4-1) Evidence of cirrhosis, including any of follows:
1. Platelet count \<100,000/mm3
2. Esophagogastric varices on endoscopy
3. Evidence of clinically significant portal hypertension
4. Fibroscan ≥ 12.0 kPa (If the test was done in 3 months before the time of screening.) and confirmed to have liver cirrhosis by an investigator
4-2) 40≤ALT levels\<70 IU/L (males) or 40≤ ALT levels\<50 IU/L (females) with evidence of significant fibrosis(F2; ≥7.2 kPa) as measured by either liver biopsy, Fibroscan or MR elastograpy performed within 3 months.
5\. Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
6\. Medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agents
7\. Received solid organ or bone marrow transplant
8\. Known hypersensitivity to study drugs, metabolites, or formulation excipients
9\. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study or unable to comply with dosing requirements
10\. Use of investigational agents within 6 months of screening, unless allowed by the Sponsor or Investigator
11\. Significant renal, cardiovascular, pulmonary, or neurological disease in the opinion of the Investigator
12\. Any malignant tumor in the preceding five years. However, a history of treated malignancy (other than HCC) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years
13\. Pregnant or breastfeeding or willing to be pregnant
14\. Participating in other clinical trials to administer medication. However, it is possible to participate if it is not an antiviral agent or immunosuppressant related clinical trial.
40 Years
80 Years
ALL
No
Sponsors
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Samsung Medical Center
OTHER
Kyunghee University Medical Center
OTHER
Chung-Ang University Hosptial, Chung-Ang University College of Medicine
OTHER
Seoul National University Hospital
OTHER
Ulsan University Hospital
OTHER
Konkuk University Medical Center
OTHER
Kyungpook National University Hospital
OTHER
Korea University Guro Hospital
OTHER
Seoul St. Mary's Hospital
OTHER
Kaohsiung Medical University
OTHER
Chang Gung Memorial Hospital
OTHER
E-DA Hospital
OTHER
Taitung Mackay Memorial Hospital
UNKNOWN
National Cheng-Kung University Hospital
OTHER
Chi Mei Medical Hospital
OTHER
Chiayi Christian Hospital
OTHER
St. Martin De Porress Hospital
OTHER
Dalin Tzu Chi General Hospital
OTHER
Taichung Veterans General Hospital
OTHER
China Medical University Hospital
OTHER
Seoul National University Bundang Hospital
OTHER
Young-Suk Lim
OTHER
Responsible Party
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Young-Suk Lim
Professor
Principal Investigators
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Young-Suk Lim, M.D, Ph D
Role: PRINCIPAL_INVESTIGATOR
Asan Medical Center
Locations
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Kyungpook National University Hospital
Daegu, , South Korea
Seoul National University Bundang Hospital
Seongnam, , South Korea
Asan Medical Center
Seoul, , South Korea
Chung-Ang University Hospital
Seoul, , South Korea
Konkuk University Hospital
Seoul, , South Korea
Korea University Guro Hospital
Seoul, , South Korea
Kyung-Hee University Hospital
Seoul, , South Korea
Samsung Medical center
Seoul, , South Korea
Seoul National University Hospital
Seoul, , South Korea
Ulsan University Hospital
Ulsan, , South Korea
Countries
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References
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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. 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.
Tseng TC, Kao JH. Treating Immune-tolerant Hepatitis B. J Viral Hepat. 2015 Feb;22(2):77-84. doi: 10.1111/jvh.12370. Epub 2014 Nov 25.
Andreani T, Serfaty L, Mohand D, Dernaika S, Wendum D, Chazouilleres O, Poupon R. Chronic hepatitis B virus carriers in the immunotolerant phase of infection: histologic findings and outcome. Clin Gastroenterol Hepatol. 2007 May;5(5):636-41. doi: 10.1016/j.cgh.2007.01.005. Epub 2007 Apr 11.
Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L, Cheung SK, Wong WM, Lau GK; Hong Kong Liver Fibrosis Study Group. Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology. 2007 Aug;46(2):395-401. doi: 10.1002/hep.21724.
Kennedy PTF, Sandalova E, Jo J, Gill U, Ushiro-Lumb I, Tan AT, Naik S, Foster GR, Bertoletti A. Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):637-645. doi: 10.1053/j.gastro.2012.06.009. Epub 2012 Jun 15.
Lai M, Hyatt BJ, Nasser I, Curry M, Afdhal NH. The clinical significance of persistently normal ALT in chronic hepatitis B infection. J Hepatol. 2007 Dec;47(6):760-7. doi: 10.1016/j.jhep.2007.07.022. Epub 2007 Sep 24.
Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, Chauhan R, Bose S. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008 May;134(5):1376-84. doi: 10.1053/j.gastro.2008.02.075. Epub 2008 Feb 29.
Kim GA, Lim YS, Han S, Choi J, Shim JH, Kim KM, Lee HC, Lee YS. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut. 2018 May;67(5):945-952. doi: 10.1136/gutjnl-2017-314904. Epub 2017 Oct 21.
Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, Huang GT, Iloeje UH; REVEAL-HBV Study Group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006 Jan 4;295(1):65-73. doi: 10.1001/jama.295.1.65.
Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006 Mar;130(3):678-86. doi: 10.1053/j.gastro.2005.11.016.
Lin ZH, Xin YN, Dong QJ, Wang Q, Jiang XJ, Zhan SH, Sun Y, Xuan SY. Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis. Hepatology. 2011 Mar;53(3):726-36. doi: 10.1002/hep.24105. Epub 2011 Feb 11.
Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J, S Sulkowski M, Torriani FJ, Dieterich DT, Thomas DL, Messinger D, Nelson M; APRICOT Clinical Investigators. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006 Jun;43(6):1317-25. doi: 10.1002/hep.21178.
Lim YS, Yu ML, Choi J, Chen CY, Choi WM, Kang W, Kim GA, Kim HJ, Lee YB, Lee JH, Park NH, Kwon SY, Park SY, Kim JH, Choi GH, Jang ES, Chen CH, Hsu YC, Bair MJ, Cheng PN, Tung HD, Chang TS, Lo CC, Tseng KC, Yang SS, Peng CY, Han S. Early antiviral treatment with tenofovir alafenamide to prevent serious clinical adverse events in adults with chronic hepatitis B and moderate or high viraemia (ATTENTION): interim results from a randomised controlled trial. Lancet Gastroenterol Hepatol. 2025 Apr;10(4):295-305. doi: 10.1016/S2468-1253(24)00431-X. Epub 2025 Feb 3.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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IN-KR-320-5358
Identifier Type: -
Identifier Source: org_study_id