Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)

NCT04939441 | Unknown Phase 4

• 1 other identifier: IN-CN-320-5613
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

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

Keywords

Chronic Hepatitis B; Liver fibrosis, Liver cirrhosis; Tenofovir alafenamide

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with fibrosis regression

  Fibrosis stage decrease at least 1 point by Ishak score or "Predominantly Regressive" by "Beijing classification"

  Week 96

• HBV DNA undetectable rate

  Serum HBV DNA \<20 IU/mL

  Week 96

Secondary Outcomes (7)

• Percentage of liver stiffness decrease >= 30%

  Week 48 and Week 96

• HBV DNA undetectable rate

  Week 24, Week 48 and Week 72

• ALT normalization rate

  Week 48 and Week 96

• HBeAg and HBsAg loss and seroconversion rate

  Week 48 and Week 96

• Changes in renal function

  Week 48 and Week 96

Study Arms (1)

TAF group

EXPERIMENTAL

TAF \[Vemlidy® 25mg QD\] monotherapy

Drug: Tenofovir alafenamide

Interventions

Tenofovir alafenamide DRUG

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

Also known as: Vemlidy®

TAF group

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jidong Jia: lead
• Beijing Ditan Hospital: collaborator
• ShuGuang Hospital: collaborator
• Tianjin Third Central Hospital: collaborator
• Huashan Hospital: collaborator
• The Sixth Peoples Hospital of Zhengzhou: collaborator
• Tianjin Second People's Hospital: collaborator
• Ruijin Hospital: collaborator
• Shanghai East Hospital: collaborator

Study Sites (7)

Beijing Ditan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100015, China

Location

Shuguang Hospital

Shanghai, Shanghai Municipality, 200021, China

Location

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Ruijin Hospital

Shanghai, Shanghai Municipality, 201199, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 310000, China

Location

Tianjin Third Central Hospital

Tianjin, Tianjin Municipality, 300170, China

Location

Tianjin Second People's Hospital

Tianjin, Tianjin Municipality, 300192, China

Location

Related Publications (3)

• 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.

  PMID: 28404091 RESULT

• 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.

  PMID: 28404092 RESULT

• 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.

  PMID: 29756595 RESULT

MeSH Terms

Conditions

Hepatitis B, Chronic; Liver Cirrhosis

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; Fibrosis

Study Officials

• Jidong Jia

  Beijing Friendship Hospital, Capital Medical Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Liver Research Center

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

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: June 25, 2021
• Study Start: April 20, 2021
• Primary Completion: May 1, 2024
• Study Completion: May 1, 2025
• Last Updated: May 23, 2023

Record last verified: 2023-05

Locations

CN (7)