Antiviral Therapy for Patients With Chronic Hepatitis B Infection

NCT05382351 | Unknown Phase 2 DMC

• 1 other identifier: Treatment for CHB infection
• Study Type: interventional
• Target: 238
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to demonstrate that antiviral therapy for patients with immune tolerance of CHB. On the basis of the original antiviral therapy of entecavir, further clarify the safety and effectiveness of entecavir combined with tenofovir amibufenamide.The investigators plan to enroll about 328 hepatitis B patients,. who are in the stage of immune tolerance. These participants will be devided into two groups randomly .Group A will receive the treatment of entecavir. Group B will be treated with entecavir and tenofovir amibufenamide. The participants in both groups will be followed up for 96 weeks. The primary endpoint is to compare the inhibition rate of HBV-DNA between two groups. The secondary endpoint includes: (1) Comparing the decrease of HBV DNA at 48 weeks between the two groups. (2) Comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups. (3) The changes of HBsAg at 48 weeks and 96 weeks between the two groups. (4) Comparing adverse side effects between the two groups.

Conditions

Chronic Hepatitis B Virus Infection

Outcome Measures

Primary Outcomes (1)

• The inhibition rate of HBV-DNA between two groups

  compare the inhibition rate of HBV-DNA between two groups at 96 weeks

  96 weeks

Secondary Outcomes (4)

• The decrease of HBV DNA in the at 48 weeks between the two groups

  48 weeks

• The HBeAg seroconversion rates at 48 weeks and 96 weeks

  48 weeks and 96 weeks

• The changes of HBsAg

  48 weeks and 96 weeks

• adverse side effects

  4、12、24、48、72 and 96 weeks

Study Arms (2)

Entecavir group

EXPERIMENTAL

Patients receive treatment with entecavir

Drug: Entecavir

Entecavir and Tenofovir Amibufenamide group

EXPERIMENTAL

Patients will receive the treatment of entecavir combined with tenofovir amibufenamide

Drug: Entecavir combined with Tenofovir Amibufenamide

Interventions

Entecavir DRUG

Entecavir group will receive entecavir orally once a day, 0.5mg each time, and fasting for 2h before and after taking the medicine

Also known as: Boludine/Rui fu en

Entecavir group

Entecavir combined with Tenofovir Amibufenamide DRUG

Entecavir combined with Tenofovir Amibufenamide group will be treated with entecavir and tenofovir amibufenamide. Entecavir is administered in the same way as before. enofovir amibufenamide orally 25mg once a day with meals

Also known as: Heng mu

Entecavir and Tenofovir Amibufenamide group

Eligibility Criteria

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

You may qualify if:

• Age between 18-65 years old;
• HBsAg positive \>6 months, HBsAg\>1\*10e4IU/ml;
• HBV-DNA\> 2 \* 10e7IU / ml;
• HBeAg positive;
• ALT / AST remained normal which were followed up twice within 1 year with at least a 6-month interval each time.
• No antiviral treatment with interferon or nucleoside (acid) analogues in the previous year

You may not qualify if:

• infection with hepatitis A, C, D, E viruses or HIV infection ;
• Combined with diabetes, hypertension, renal insufficiency, autoimmune diseases and other organ dysfunction And malignant tumors;
• Patients using Immunosuppressive therapy or radiotherapy / chemotherapy for other diseases;
• Patients with liver fibrosis, cirrhosis (FibroScan \> = 9.4kpa) and liver cancer were identified;
• Extrahepatic manifestations related to HBV (glomerulonephritis, vasculitis, nodular polyarteritis, peripheral neuropathy, etc.);
• Allergic to nucleoside drugs
• Pregnancy or having pregnancy plan within 2 years and Lactating patients;
• Patients who are unable to comply with the arrange ment of this study or sign the informed consent.
• Failed to return to hospital regularly for follow-up ac- cording to the study plan.
• Researchers determine other condition that does not fit into the study.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

RECRUITING

Related Publications (18)

• Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008 Feb;48(2):335-52. doi: 10.1016/j.jhep.2007.11.011. Epub 2007 Dec 4.

  PMID: 18096267 BACKGROUND

• Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available.

  PMID: 17256718 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

• Tang LSY, Covert E, Wilson E, Kottilil S. Chronic Hepatitis B Infection: A Review. JAMA. 2018 May 1;319(17):1802-1813. doi: 10.1001/jama.2018.3795.

  PMID: 29715359 BACKGROUND

• Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int. 2016 Sep;36(9):1239-51. doi: 10.1111/liv.13142. Epub 2016 May 22.

  PMID: 27062182 BACKGROUND

• Chayanupatkul M, Omino R, Mittal S, Kramer JR, Richardson P, Thrift AP, El-Serag HB, Kanwal F. Hepatocellular carcinoma in the absence of cirrhosis in patients with chronic hepatitis B virus infection. J Hepatol. 2017 Feb;66(2):355-362. doi: 10.1016/j.jhep.2016.09.013. Epub 2016 Sep 28.

  PMID: 27693539 BACKGROUND

• Wong GL, Chan HL, Chan HY, Tse PC, Tse YK, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Wong VW. Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology. 2013 May;144(5):933-44. doi: 10.1053/j.gastro.2013.02.002. Epub 2013 Feb 12.

  PMID: 23415803 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

• Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, Chan HY, Chan FK, Sung JJ, Chan HL. Clinical factors associated with liver stiffness in hepatitis B e antigen-positive chronic hepatitis B patients. Clin Gastroenterol Hepatol. 2009 Feb;7(2):227-33. doi: 10.1016/j.cgh.2008.10.023. Epub 2008 Oct 30.

  PMID: 19121647 BACKGROUND

• Seto WK, Lai CL, Ip PP, Fung J, Wong DK, Yuen JC, Hung IF, Yuen MF. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B. PLoS One. 2012;7(2):e32622. doi: 10.1371/journal.pone.0032622. Epub 2012 Feb 28.

  PMID: 22389715 BACKGROUND

• Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016 Jan;63(1):284-306. doi: 10.1002/hep.28280. Epub 2015 Nov 13.

  PMID: 26566246 BACKGROUND

• Wong GL, Wong VW, Chan HY, Tse PC, Wong J, Chim AM, Yiu KK, Chu SH, Chan HL. Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years. Aliment Pharmacol Ther. 2012 Jun;35(11):1326-35. doi: 10.1111/j.1365-2036.2012.05098.x. Epub 2012 Apr 16.

  PMID: 22506552 BACKGROUND

• Wong GL, Chan HL, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Lai JW, Lo AO, Chan HY, Wong VW. Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis. Hepatology. 2013 Nov;58(5):1537-47. doi: 10.1002/hep.26301. Epub 2013 Sep 30.

  PMID: 23389810 BACKGROUND

• Zoutendijk R, Reijnders JG, Zoulim F, Brown A, Mutimer DJ, Deterding K, Hofmann WP, Petersen J, Fasano M, Buti M, Berg T, Hansen BE, Sonneveld MJ, Wedemeyer H, Janssen HL; VIRGIL Surveillance Study Group. Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis. Gut. 2013 May;62(5):760-5. doi: 10.1136/gutjnl-2012-302024. Epub 2012 Apr 5.

  PMID: 22490523 BACKGROUND

• Lok AS, Trinh H, Carosi G, Akarca US, Gadano A, Habersetzer F, Sievert W, Wong D, Lovegren M, Cohen D, Llamoso C. Efficacy of entecavir with or without tenofovir disoproxil fumarate for nucleos(t)ide-naive patients with chronic hepatitis B. Gastroenterology. 2012 Sep;143(3):619-628.e1. doi: 10.1053/j.gastro.2012.05.037. Epub 2012 May 27.

  PMID: 22643350 BACKGROUND

• Chan HL, Chan CK, Hui AJ, Chan S, Poordad F, Chang TT, Mathurin P, Flaherty JF, Lin L, Corsa A, Gaggar A, Subramanian GM, McHutchison JG, Lau G, Lee S, Gane EJ. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA. Gastroenterology. 2014 May;146(5):1240-8. doi: 10.1053/j.gastro.2014.01.044. Epub 2014 Jan 23.

  PMID: 24462735 BACKGROUND

• Mauss S, Berger F, Filmann N, Hueppe D, Henke J, Hegener P, Athmann C, Schmutz G, Herrmann E. Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B. J Hepatol. 2011 Dec;55(6):1235-40. doi: 10.1016/j.jhep.2011.03.030. Epub 2011 May 19.

  PMID: 21703180 BACKGROUND

• Duarte-Rojo A, Heathcote EJ. Efficacy and safety of tenofovir disoproxil fumarate in patients with chronic hepatitis B. Therap Adv Gastroenterol. 2010 Mar;3(2):107-19. doi: 10.1177/1756283X09354562.

  PMID: 21180595 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Exploratory study on antiviral therapy for patients with chronic hepatitis B virus infection (immune tolerance period)

Study Record Dates

• First Submitted: May 15, 2022
• First Posted: May 19, 2022
• Study Start: May 10, 2022
• Primary Completion: April 30, 2024
• Study Completion: December 31, 2024
• Last Updated: May 19, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)