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Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)

Primary Purpose

Chronic Hepatitis B

Status
Active
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Tenofovir alafenamide
Sponsored by
Jidong Jia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Chronic Hepatitis B, Liver fibrosis, Liver cirrhosis, Tenofovir alafenamide

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beijing Ditan Hospital, Capital Medical University
  • Shuguang Hospital
  • Huashan Hospital Fudan University
  • Ruijin Hospital
  • Shanghai East Hospital
  • Tianjin Third Central Hospital
  • Tianjin Second People's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TAF group

Arm Description

TAF [Vemlidy® 25mg QD] monotherapy

Outcomes

Primary Outcome Measures

Proportion of patients with fibrosis regression
Fibrosis stage decrease at least 1 point by Ishak score or "Predominantly Regressive" by "Beijing classification"
HBV DNA undetectable rate
Serum HBV DNA <20 IU/mL

Secondary Outcome Measures

Percentage of liver stiffness decrease >= 30%
Proportion of patients with liver stiffness decrease >= 30% from baseline to week 48 and 96
HBV DNA undetectable rate
HBV DNA undetectable rate at week 24, 48, and 72
ALT normalization rate
Proportion of patients with ALT <= 1.0xULN
HBeAg and HBsAg loss and seroconversion rate
Proportions of patients with HBsAg loss and seroconversion to anti-HBs, and proportions of patients with HBeAg loss and seroconversion to anti-HBe.
Changes in renal function
Changes of eGFR (estimated Glomerular Filtration rate) from baseline to week 48 and 96
Changes of bone mineral density
Percentage changes in spine BMD and hip BMD from baseline to week 48 and 96
Incidence of liver-related endpoint events
liver-related endpoint events: decompensation, HCC, liver transplantation, liver-related death

Full Information

First Posted
June 17, 2021
Last Updated
May 20, 2023
Sponsor
Jidong Jia
Collaborators
Beijing Ditan Hospital, ShuGuang Hospital, Tianjin Third Central Hospital, Huashan Hospital, The Sixth Peoples Hospital of Zhengzhou, Tianjin Second People's Hospital, Ruijin Hospital, Shanghai East Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04939441
Brief Title
Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)
Official Title
Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF) in Treatment-Naive CHB Related Fibrosis/Cirrhosis: a 96w Open-label Multicenter Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 20, 2021 (Actual)
Primary Completion Date
May 1, 2024 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jidong Jia
Collaborators
Beijing Ditan Hospital, ShuGuang Hospital, Tianjin Third Central Hospital, Huashan Hospital, The Sixth Peoples Hospital of Zhengzhou, Tianjin Second People's Hospital, Ruijin Hospital, Shanghai East Hospital

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Chronic Hepatitis B, Liver fibrosis, Liver cirrhosis, Tenofovir alafenamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Subjects will be treated for 96 weeks with TAF [Vemlidy® 25mg QD] monotherapy
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TAF group
Arm Type
Experimental
Arm Description
TAF [Vemlidy® 25mg QD] monotherapy
Intervention Type
Drug
Intervention Name(s)
Tenofovir alafenamide
Other Intervention Name(s)
Vemlidy®
Intervention Description
Subjects will be treated for 96 weeks with TAF [Vemlidy® 25mg QD] monotherapy
Primary Outcome Measure Information:
Title
Proportion of patients with fibrosis regression
Description
Fibrosis stage decrease at least 1 point by Ishak score or "Predominantly Regressive" by "Beijing classification"
Time Frame
Week 96
Title
HBV DNA undetectable rate
Description
Serum HBV DNA <20 IU/mL
Time Frame
Week 96
Secondary Outcome Measure Information:
Title
Percentage of liver stiffness decrease >= 30%
Description
Proportion of patients with liver stiffness decrease >= 30% from baseline to week 48 and 96
Time Frame
Week 48 and Week 96
Title
HBV DNA undetectable rate
Description
HBV DNA undetectable rate at week 24, 48, and 72
Time Frame
Week 24, Week 48 and Week 72
Title
ALT normalization rate
Description
Proportion of patients with ALT <= 1.0xULN
Time Frame
Week 48 and Week 96
Title
HBeAg and HBsAg loss and seroconversion rate
Description
Proportions of patients with HBsAg loss and seroconversion to anti-HBs, and proportions of patients with HBeAg loss and seroconversion to anti-HBe.
Time Frame
Week 48 and Week 96
Title
Changes in renal function
Description
Changes of eGFR (estimated Glomerular Filtration rate) from baseline to week 48 and 96
Time Frame
Week 48 and Week 96
Title
Changes of bone mineral density
Description
Percentage changes in spine BMD and hip BMD from baseline to week 48 and 96
Time Frame
Week 48 and Week 96
Title
Incidence of liver-related endpoint events
Description
liver-related endpoint events: decompensation, HCC, liver transplantation, liver-related death
Time Frame
Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jidong Jia
Organizational Affiliation
Beijing Friendship Hospital, Capital Medical Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beijing Ditan Hospital, Capital Medical University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100015
Country
China
Facility Name
Shuguang Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200021
Country
China
Facility Name
Huashan Hospital Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Facility Name
Ruijin Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201199
Country
China
Facility Name
Shanghai East Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
310000
Country
China
Facility Name
Tianjin Third Central Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300170
Country
China
Facility Name
Tianjin Second People's Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300192
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
28404091
Citation
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. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
Results Reference
result
PubMed Identifier
28404092
Citation
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. Erratum In: Lancet Gastroenterol Hepatol. 2016 Nov;1(3):e2.
Results Reference
result
PubMed Identifier
29756595
Citation
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.
Results Reference
result

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Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)

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