HBsAg Seroclearance in Adults With HBV Related Liver Fibrosis After Receiving Combined Therapy of Peg-IFN and Tenofovir.

A Multicentre Clinical Trial in HBsAg Seroclearance After Receiving Combined Therapy of Peginterferon and Tenofovir in Nucleos(t)Ide Analogue-treated Patients With HBV Related Liver Fibrosis.

Liver fibrosis caused by hepatitis B virus (HBV) infection is easy to progress to liver cirrhosis and liver cancer, with great harm and poor therapeutic effect. Nucleos(t)ide analogues (NAs) are the most commonly anti-HBV drugs currently . Long-term use of NAs can inhibit HBV DNA and achieve the purpose of reducing poor prognosis. However, adverse prognosis, such as liver cirrhosis and liver cancer, cannot be completely eliminated even under the status of virologic inhibition under THE action of NAs. Current studies have shown that the lower the HBV surface antigen (HBsAg) is, the better the long-term prognosis is. As another anti-HBV drug, pegylated-interferon-α (peg-IFN-α) has the immune regulation effect that NAs do not have, which can bring irreplaceable effects in HBsAg reduction and liver fibrosis reversal. Therefore, the combined therapy of NAs and peg-IFN-α is a hot issue in the field of liver diseases over the world, but the research and application of the combined therapy in patients with liver fibrosis are very few. The preliminary results of our previous research showed that the combined therapy of peg-IFN-α and NAs in patients with HBV related fibrosis were safe, and had a significant effect on HBsAg decline. On this basis, this study intends to carry out a multicentre, non-randomized concurrent controlled trial, comparing the safety and efficacy between combined therapy (peg-IFN-α plus tenofovir) and tenofovir monotherapy in patients with liver fibrosis, especially focusing on HBsAg's decline and clearance, and the improvement of liver fibrosis degree, in order to find a better therapy, and to guide the clinical decision making.

Study Overview

• Status: Recruiting
• Conditions: Liver Fibrosis
• Intervention / Treatment: Drug: Tenofovir Disoproxil Fumarate; Drug: PEG-Interferon Alfa, Tenofovir Disoproxil Fumarate

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • Third Affiliated Hospital of Sun Yat-sen University
      • Contact: Liang Peng, Doctor; Phone Number: +8613533978874; Email: pzp33@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Positive hepatitis b surface antigen; 2.Infection of hepatitis b virus DNA > 0.5 year before anti-HBV treatment; 3.Receiving treatment of nucleoside/nucleotide analogues at least one year before recruited; 4.Age from 18 to 55 years old; 5.Normal liver function(ALT<ULN,AST<ULN and TBil<ULN); 6.Undetectable hepatitis b virus DNA or less than 100IU/ml; 7.Liver biopsy suggested fibrosis of liver into F1~F3(Metavir score system) or LSM between 6 and 12 kpa measured by fibroscan; 8.Liver ultrasound: normal or echo thickening, and portal vein diameter ≤ 12mm.

Exclusion Criteria:

• 1.Decompensated cirrhosis, hepatocellular carcinoma or other malignancy; 2.Pregnancy, lactation or female has plan of pregnancy within 18 months; 3.Accompanied with other active liver diseases(HAV, HCV, HDV, HEV, autoimmune liver disease, drug-induced liver injury, alcoholic liver disease, genetic metabolic liver disease, etc.)； 4.Accompanied with human immunodeficiency virus infection or congenital immune deficiency diseases; 5.Accompanied with severe diabetes, autoimmune diseases etc. and other important organ dysfunctions; 6.Patients who fail to comply with this research arrangement and sign an informed consent form; 7.Patients can not follow-up; 8.Investigator considering inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TDF group; tenofovir 300mg taken orally per day.	Drug: Tenofovir Disoproxil Fumarate; TDF monotherapy
Experimental: peg-IFN-α plus TDF group; peg-IFN-α 180ug given subcutaneous injection per week combined with tenofovir 300mg taken orally per day .	Drug: PEG-Interferon Alfa, Tenofovir Disoproxil Fumarate; Combination therapy group was treated with PEG-interferon Alfa in addition to TDF monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of HBsAg seroclearance/seroconversion	proportion of seroclearance or seroconversion of HBV surface antigen compared with baseline	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of HBsAg seroclearance/seroconversion	Proportion of seroclearance or seroconversion of HBV surface antigen compared with baseline	96 weeks
proportion of fibrosis improvement	Proportion of patients with improved fibrosis compared with baseline	96 weeks

Collaborators and Investigators

• Sponsor: Third Affiliated Hospital, Sun Yat-Sen University

Publications and helpful links

General Publications

• Zhu S, Wu L, Mei Y, Liu Z, Lin L, Yuan J, Li J, Li X, Peng L. Prospective, multicentre, randomised controlled trial comparing the seroclearance of HBsAg between combination therapy of peg-interferon alpha and tenofovir with tenofovir monotherapy in nucleos(t)ide analogue-experienced patients with HBV-related liver fibrosis: a study protocol. BMJ Open. 2021 Oct 25;11(10):e049104. doi: 10.1136/bmjopen-2021-049104.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: November 17, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Immunologic Factors; Tenofovir; Interferons; Interferon-alpha
• Other Study ID Numbers: PL15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No