Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)

NCT ID: NCT04939441

Last Updated: 2023-05-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-20
• Study Completion Date: 2025-05-01

Brief Summary

Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection. Whereas, the long-term effect of TAF to liver fibrosis is still unknown. Here, we enrolled treatment naive CHB patients with biopsy-proven significant fibrosis (METAVIR fibrosis stage ≥ F2). All enrolled subjects will be treated with TAF monotherapy for 96 weeks. After 96 weeks of therapy, the second liver biopsy will be performed to evaluate the rate of liver fibrosis regression. During this study, all subjects will be assessed for laboratory tests, imaging examination at baseline, first 12-week and every 24-week during follow-up.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TAF group

TAF \[Vemlidy® 25mg QD\] monotherapy

Group Type: EXPERIMENTAL

Tenofovir alafenamide

Intervention Type: DRUG

Subjects will be treated for 96 weeks with TAF \[Vemlidy® 25mg QD\] monotherapy

Interventions

Tenofovir alafenamide

Subjects will be treated for 96 weeks with TAF \[Vemlidy® 25mg QD\] monotherapy

Intervention Type: DRUG

Other Intervention Names

Vemlidy®

Eligibility Criteria

Inclusion Criteria

• 18-69 years old (inclusive);
• BMI (18-30 kg/m2);
• Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months; or chronic hepatitis B proven by live biopsy;
• Not received nucleoside (acid) analogue and/or interferon therapy (treatment-naive);
• Liver biopsy performed within 6 months before treatment and had readable biopsy slides or agrees to have a biopsy performed prior to baseline;
• METAVIR fibrosis stage ≥ F2;
• For patients without cirrhosis (F2/3), HBV DNA levels >2000 IU/mL before treatment; For patients with cirrhosis (F4), HBV DNA >20 IU/mL before treatment;
• ALT≤10 ULN before treatment;
• Creatinine clearance ≥ 50 mL/min;
• Agreement not to undertake other HBV systemic antiviral or interferon (IFN) regimens during participation in this study;
• Willing and able to provide written informed consent.

Exclusion Criteria

• Patients with Child-Turcotte-Pugh（CTP）score ≥ 7;
• Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or liver transplantation;
• Patients co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV), or alcoholic liver diseases, autoimmune liver disease, genetic liver disease, drug-induced liver injury, non-alcoholic fatty liver disease or other chronic liver diseases;
• Patients with evidence of hepatocellular carcinoma (HCC) by imaging with or without AFP;
• Patients with other uncured malignant tumors;
• Patients with organ or bone marrow transplantation;
• Patients currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion;
• Patients who are allergic to any component of TAF;
• Patients who recently or newly started bisphosphate (within 1 month);
• Patients with active alcohol or drug abuse or history of alcohol or drug abuse (hinder compliance with treatment, or participation in the study or interpretation of results considered by the Investigator);
• Patients with significant renal, cardiovascular, pulmonary, or neurological disease
• Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study;
• Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study;
• Not suitable for this study identified by researchers.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Ditan Hospital

OTHER

Sponsor Role: collaborator

ShuGuang Hospital

OTHER

Sponsor Role: collaborator

Tianjin Third Central Hospital

OTHER

Sponsor Role: collaborator

Huashan Hospital

OTHER

Sponsor Role: collaborator

The Sixth Peoples Hospital of Zhengzhou

UNKNOWN

Sponsor Role: collaborator

Tianjin Second People's Hospital

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Shanghai East Hospital

OTHER

Sponsor Role: collaborator

Jidong Jia

OTHER

Sponsor Role: lead

Responsible Party

Jidong Jia

Director of Liver Research Center

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Jidong Jia

Role: PRINCIPAL_INVESTIGATOR

Beijing Friendship Hospital, Capital Medical Hospital

Locations

Beijing Ditan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Shuguang Hospital

Shanghai, Shanghai Municipality, China

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Ruijin Hospital

Shanghai, Shanghai Municipality, China

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Tianjin Third Central Hospital

Tianjin, Tianjin Municipality, China

Tianjin Second People's Hospital

Tianjin, Tianjin Municipality, China

Countries

China

References

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.

Reference Type: RESULT

PMID: 28404091 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28404092 (View on PubMed)

Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, Sharma M, Janssen HLA, Pan CQ, Celen MK, Furusyo N, Shalimar D, Yoon KT, Trinh H, Flaherty JF, Gaggar A, Lau AH, Cathcart AL, Lin L, Bhardwaj N, Suri V, Mani Subramanian G, Gane EJ, Buti M, Chan HLY; GS-US-320-0110; GS-US-320-0108 Investigators. 96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.

Reference Type: RESULT

PMID: 29756595 (View on PubMed)

Other Identifiers

IN-CN-320-5613

Identifier Type: -

Identifier Source: org_study_id