search
Back to results

Antiviral Therapy for Patients With Chronic Hepatitis B Infection

Primary Purpose

Chronic Hepatitis B Virus Infection

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Entecavir
Entecavir combined with Tenofovir Amibufenamide
Sponsored by
Sun Yat-sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B Virus Infection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

  • The Third Affiliated Hospital of Sun Yat-sen UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Entecavir group

Entecavir and Tenofovir Amibufenamide group

Arm Description

Patients receive treatment with entecavir

Patients will receive the treatment of entecavir combined with tenofovir amibufenamide

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

The decrease of HBV DNA in the at 48 weeks between the two groups
comparing the decrease of HBV DNA in the at 48 weeks between the two groups
The HBeAg seroconversion rates at 48 weeks and 96 weeks
comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups
The changes of HBsAg
The changes of HBsAg at 48 weeks and 96 weeks were compared between the two groups
adverse side effects
comparing adverse side effects between the two groups

Full Information

First Posted
May 15, 2022
Last Updated
May 15, 2022
Sponsor
Sun Yat-sen University
search

1. Study Identification

Unique Protocol Identification Number
NCT05382351
Brief Title
Antiviral Therapy for Patients With Chronic Hepatitis B Infection
Official Title
Exploratory Study on Antiviral Therapy for Patients With Chronic Hepatitis B Virus Infection (Immune Tolerance Period)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 10, 2022 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
High HBV DNA level is an independent risk factor for liver cirrhosis and liver cancer, we know all patients with chronic hepatitis B virus infection in immune tolerance period had high viral load. So it is necessary to implement antiviral therapy for patients with chronic hepatitis B virus infection in immune tolerance period.Previous studies have found that combination of two antiviral drugs has a higher virological inhibition rate in patients with high viral load than single drug. Hence, the investigators' hypothesis is that treatment of patients with chronic hepatitis B virus infection in immune tolerance period result in higher virological inhibition rate and reduce of the risk of cirrhosis and liver cancer. The investigators plan to enroll about 328 hepatitis B patients, who are in the stage of immune tolerance. These participants will be devided into 2 groups.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. Unless there are serious adverse drug reactions, the protocol cannot be adjusted within 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B Virus Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
238 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Entecavir group
Arm Type
Experimental
Arm Description
Patients receive treatment with entecavir
Arm Title
Entecavir and Tenofovir Amibufenamide group
Arm Type
Experimental
Arm Description
Patients will receive the treatment of entecavir combined with tenofovir amibufenamide
Intervention Type
Drug
Intervention Name(s)
Entecavir
Other Intervention Name(s)
Boludine/Rui fu en
Intervention Description
Entecavir group will receive entecavir orally once a day, 0.5mg each time, and fasting for 2h before and after taking the medicine
Intervention Type
Drug
Intervention Name(s)
Entecavir combined with Tenofovir Amibufenamide
Other Intervention Name(s)
Heng mu
Intervention Description
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
Primary Outcome Measure Information:
Title
The inhibition rate of HBV-DNA between two groups
Description
compare the inhibition rate of HBV-DNA between two groups at 96 weeks
Time Frame
96 weeks
Secondary Outcome Measure Information:
Title
The decrease of HBV DNA in the at 48 weeks between the two groups
Description
comparing the decrease of HBV DNA in the at 48 weeks between the two groups
Time Frame
48 weeks
Title
The HBeAg seroconversion rates at 48 weeks and 96 weeks
Description
comparing the HBeAg seroconversion rates at 48 weeks and 96 weeks between the two groups
Time Frame
48 weeks and 96 weeks
Title
The changes of HBsAg
Description
The changes of HBsAg at 48 weeks and 96 weeks were compared between the two groups
Time Frame
48 weeks and 96 weeks
Title
adverse side effects
Description
comparing adverse side effects between the two groups
Time Frame
4、12、24、48、72 and 96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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.
Facility Information:
Facility Name
The Third Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510630
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bingliang Lin, Doctor
Phone
86-20-85253165
Email
lamikin@126.com
First Name & Middle Initial & Last Name & Degree
jing Xiong, Master
Phone
86-20-85253165
Email
373599983@qq.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
18096267
Citation
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.
Results Reference
background
PubMed Identifier
17256718
Citation
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39. doi: 10.1002/hep.21513. No abstract available. Erratum In: Hepatology. 2007 Jun;45(6):1347.
Results Reference
background
PubMed Identifier
16391218
Citation
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.
Results Reference
background
PubMed Identifier
29715359
Citation
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. Erratum In: JAMA. 2018 Sep 18;320(11):1202.
Results Reference
background
PubMed Identifier
27062182
Citation
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.
Results Reference
background
PubMed Identifier
27693539
Citation
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.
Results Reference
background
PubMed Identifier
23415803
Citation
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.
Results Reference
background
PubMed Identifier
18471514
Citation
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.
Results Reference
background
PubMed Identifier
19121647
Citation
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.
Results Reference
background
PubMed Identifier
22389715
Citation
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.
Results Reference
background
PubMed Identifier
26566246
Citation
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.
Results Reference
background
PubMed Identifier
22506552
Citation
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.
Results Reference
background
PubMed Identifier
23389810
Citation
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.
Results Reference
background
PubMed Identifier
22490523
Citation
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.
Results Reference
background
PubMed Identifier
22643350
Citation
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.
Results Reference
background
PubMed Identifier
24462735
Citation
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. Erratum In: Gastroenterology. 2015 Jan;148(1):263. Lau, George [added].
Results Reference
background
PubMed Identifier
21703180
Citation
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.
Results Reference
background
PubMed Identifier
21180595
Citation
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.
Results Reference
background

Learn more about this trial

Antiviral Therapy for Patients With Chronic Hepatitis B Infection

We'll reach out to this number within 24 hrs