Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)

Chronic Hepatitis B Clinical Trial

Official title:

Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF) in Treatment-Naive CHB Related Fibrosis/Cirrhosis: a 96w Open-label Multicenter Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04939441
• Other study ID #: IN-CN-320-5613
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: April 20, 2021
• Est. completion date: May 1, 2025

Study information

• Verified date: May 2023
• Source: Beijing Friendship Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Fibrosis
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Liver Cirrhosis

Intervention

Drug:
• Tenofovir alafenamide
Subjects will be treated for 96 weeks with TAF [Vemlidy® 25mg QD] monotherapy

Locations

Country	Name	City	State
China	Beijing Ditan Hospital, Capital Medical University	Beijing	Beijing
China	Huashan Hospital Fudan University	Shanghai	Shanghai
China	Ruijin Hospital	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	Shuguang Hospital	Shanghai	Shanghai
China	Tianjin Second People's Hospital	Tianjin	Tianjin
China	Tianjin Third Central Hospital	Tianjin	Tianjin

Sponsors (9)

Lead Sponsor	Collaborator
Jidong Jia	Beijing Ditan Hospital, Huashan Hospital, Ruijin Hospital, Shanghai East Hospital, ShuGuang Hospital, The Sixth Peoples Hospital of Zhengzhou, Tianjin Second People's Hospital, Tianjin Third Central Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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 S — View 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 Inve — View 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 Investig — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with fibrosis regression	Fibrosis stage decrease at least 1 point by Ishak score or "Predominantly Regressive" by "Beijing classification"	Week 96
Primary	HBV DNA undetectable rate	Serum HBV DNA <20 IU/mL	Week 96
Secondary	Percentage of liver stiffness decrease >= 30%	Proportion of patients with liver stiffness decrease >= 30% from baseline to week 48 and 96	Week 48 and Week 96
Secondary	HBV DNA undetectable rate	HBV DNA undetectable rate at week 24, 48, and 72	Week 24, Week 48 and Week 72
Secondary	ALT normalization rate	Proportion of patients with ALT <= 1.0xULN	Week 48 and Week 96
Secondary	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.	Week 48 and Week 96
Secondary	Changes in renal function	Changes of eGFR (estimated Glomerular Filtration rate) from baseline to week 48 and 96	Week 48 and Week 96
Secondary	Changes of bone mineral density	Percentage changes in spine BMD and hip BMD from baseline to week 48 and 96	Week 48 and Week 96
Secondary	Incidence of liver-related endpoint events	liver-related endpoint events: decompensation, HCC, liver transplantation, liver-related death	Week 96