Effectiveness of TAF in Reducing Clinical Events in CHB Patients Beyond Treatment Indications by Current Guidelines

NCT03753074 | Active Not Recruiting Phase 4

• 1 other identifier: IN-KR-320-5358
• Study Type: interventional
• Target: 780
• Locations: 1 country
• Sites: 10

Brief Summary

Treatment with Tenofovir Alafenamide(TAF) in Chronic Hepatitis B (CHB) patients classified as beyond treatment indication of current international guidelines (e.g. aged more than 40 years old and 4 ≤ log HBV-DNA IU/mL \< 8) is expected to bring improvement in long-term clinical outcomes. This expected result may expand the treatment indications in patients with CHB based on age and HBV-DNA in contrast to current international guidelines of CHB.

Conditions

Chronic Hepatitis b

Outcome Measures

Primary Outcomes (1)

• the occurrence of composite events during follow-up observation

  the occurrence of composite events during follow-up observation(including death, liver transplantation, or decompensated liver diseases \[Child-Pugh score≥7\], complications of portal hypertension \[ascites, gastroesophageal varices\] or HCC

  At year 4

Secondary Outcomes (27)

• Cumulative rate of patients with clinical events

  At year 4, 8 and 12

• Cumulative incidence rate of HCC

  At year 4, 8 and 12

• All-cause mortality

  At year 4, 8 and 12

• Cumulative incidence rate of liver transplantation

  At year 4, 8 and 12

• Cumulative incidence rate of liver decompensation

  At year 4, 8 and 12

Study Arms (2)

Treatment Arm A (TAF)

EXPERIMENTAL

390 subjects administered Tenofovir Alafenamide 25 mg once daily

Drug: Tenofovir Alafenamide

Treatment Arm B (Best supportive care)

NO INTERVENTION

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).

Interventions

Tenofovir Alafenamide DRUG

Tenofovir Alafenamide 25mg, Tablet, Oral, Daily

Also known as: Vemlidy

Treatment Arm A (TAF)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
• Male or female, 40 to 80 years of age
• Positive for HBsAg or HBV DNA for at least 6 months or more
• HBeAg positive or negative
• No evidence of liver cirrhosis (platelet count ≥100,000/mm3)
• serum HBV DNA ≥ 4 log10 IU/mL and ≤ 8 log10 IU/mL
• Serum ALT level \<70 if male, \<50 if female
• Estimated creatinine clearance ≥ 30 ml/min based on serum creatinine as measured at the screening evaluation
• Patient is willing and able to comply with all study requirements

You may not qualify if:

• Co-infection with HCV, HDV, HIV (Confirmed by nucleic acid tests)
• Abusing alcohol (more than 60 g/day) or illicit drugs
• Patients with history of hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)
• ) Evidence of cirrhosis, including any of follows:
• Platelet count \<100,000/mm3
• Esophagogastric varices on endoscopy
• Evidence of clinically significant portal hypertension
• 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
• ) 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.
• \. Received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
• \. Medical condition that requires concurrent use of systemic corticosteroid or other immunosuppressive agents
• \. Received solid organ or bone marrow transplant
• \. Known hypersensitivity to study drugs, metabolites, or formulation excipients
• \. 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
• \. Use of investigational agents within 6 months of screening, unless allowed by the Sponsor or Investigator

Sponsors & Collaborators

• Young-Suk Lim: lead
• Samsung Medical Center: collaborator
• Kyunghee University Medical Center: collaborator
• Chung-Ang University Hosptial, Chung-Ang University College of Medicine: collaborator
• Seoul National University Hospital: collaborator
• Ulsan University Hospital: collaborator
• Konkuk University Medical Center: collaborator
• Kyungpook National University Hospital: collaborator
• Korea University Guro Hospital: collaborator
• Seoul St. Mary's Hospital: collaborator
• Kaohsiung Medical University: collaborator
• Chang Gung Memorial Hospital: collaborator
• E-DA Hospital: collaborator
• Taitung Mackay Memorial Hospital: collaborator
• National Cheng-Kung University Hospital: collaborator
• Chi Mei Medical Hospital: collaborator
• Chiayi Christian Hospital: collaborator
• St. Martin De Porress Hospital: collaborator
• Dalin Tzu Chi General Hospital: collaborator
• Taichung Veterans General Hospital: collaborator
• China Medical University Hospital: collaborator
• Seoul National University Bundang Hospital: collaborator

Study Sites (10)

Kyungpook National University Hospital

Daegu, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Chung-Ang University Hospital

Seoul, South Korea

Location

Konkuk University Hospital

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Kyung-Hee University Hospital

Seoul, South Korea

Location

Samsung Medical center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Ulsan University Hospital

Ulsan, South Korea

Location

Related Publications (14)

• 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

• 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.

  PMID: 25424771 BACKGROUND

• 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.

  PMID: 17428739 BACKGROUND

• 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.

  PMID: 17628874 BACKGROUND

• 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.

  PMID: 22710188 BACKGROUND

• 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.

  PMID: 17928090 BACKGROUND

• 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.

  PMID: 18471514 BACKGROUND

• 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.

  PMID: 29055908 BACKGROUND

• 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.

  PMID: 16391218 BACKGROUND

• 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.

  PMID: 16530509 BACKGROUND

• 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.

  PMID: 21319189 BACKGROUND

• 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.

  PMID: 16729309 BACKGROUND

• 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.

  PMID: 39914435 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Young-Suk Lim, M.D, Ph D

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 22, 2018
• First Posted: November 26, 2018
• Study Start: February 18, 2019
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10)