A Prospective Study to Evaluate Peginterferon in Reducing the Incidence of HCC in CHB Patients

May 23, 2023 updated by: Qing XIe

A Prospective, Randomized, Open-label, Multicenter Study to Evaluate the Peginterferon, Comparing to Nucleos(t)Ide Analogues, in Reducing the Incidence of HCC in Chronic Hepatitis B Patients With Intermediate to High Liver Cancer Risks

China's new cases and deaths of hepatocellular carcinoma (HCC) rank first in the world. hepatocellular carcinoma is the third most morbid, second-most mortal malignancy in China. Up to 80% of hepatocellular carcinoma patients caused by HBV infection. Antiviral therapy can significantly reduce the incidence and mortality of hepatocellular carcinoma in patients with chronic hepatitis B (CHB), hinder the progression of liver disease, and effectively control the disease. However, studies in recent years have found that long-term therapy with Nucleos(t)ide analogue (NAs) cannot completely eliminate the risk of liver cancer in patients with chronic hepatitis B. In addition, a number of retrospective studies at home and abroad have shown that compared with long-term oral NAs, peginterferon can significantly reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis B. However, there is limit prospective studies.

This multicenter, randomized, open-label, controlled trial study is aim to evaluate the pegylated interferon alfa-2b injection in comparing to NAs in reducing the incidence of hepatocellular carcinoma, to provide evidences for new management and treatment strategy options for improving clinical outcomes for the chronic hepatitis B patients. About 267 chronic hepatitis patients with intermediate to high risk of liver cancer who are now receiving nucleoside therapy will be enrolled. Subjects will be randomized into the peginterferon combined NAs group and the NAs monotherapy group at a ratio of 2:1. Level of HBsAg, proportion of patients with HBsAg clearance and seroconversion, incidence of liver cirrhosis and hepatocellular carcinoma will be assessed.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

267

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Chengdu, China
        • Recruiting
        • The Public Health Clinical Center Of Chengdu
        • Contact:
      • Hefei, China
        • Recruiting
        • The First Affiliated Hospital of USTC Anhui Provincial Hospital
        • Contact:
      • Qingdao, China
        • Recruiting
        • The Affiliated Hospital of Qingdao University
        • Contact:
          • Yuan Guo
      • Shanghai, China
        • Recruiting
        • Ruijin Hospital Shanghai Jiao Tong University School of Medicine
        • Contact:
          • Qing Xie
      • Shanghai, China
        • Recruiting
        • Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine
        • Contact:
      • Shanghai, China
        • Recruiting
        • Tongren Hospital Shanghai Jiao Tong University School Of Medicine
        • Contact:
      • Suzhou, China
        • Recruiting
        • The Fifth People's Hospital of Suzhou
        • Contact:
      • Xiamen, China
        • Recruiting
        • Xiamen Hospital of Traditional Chinese Medicin
        • Contact:
      • Xinxiang, China
        • Recruiting
        • The Tirth Affiliated Hospital Of Xinxiang Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged 18 to 60 years and no gender limit (including 18 and 60 years).
  • HBsAg positive for more than 6 months.

  • Patients with intermediate to high liver cancer risks. Refers to if at least one of the following items is met.

    • Male patient aged above 40 years.
    • Patients with a history of cirrhosis and/or family history of liver cancer.
    • Patients with metabolic diseases, such as diabetes, fatty liver, etc.
    • Any liver cancer assessment model of chronic hepatitis B patients suggested that liver cancer was at intermediate to high risk.
  • Have received Nucleos(t)ide analogue treatment for more than 24 weeks, and currently receiving Nucleos(t)ide analogue, while HBV DNA is undetectable (HBV DNA below 300 IU/mL or 1000 copies/mL).
  • Urine and/or serum pregnancy test within 24 hours prior to the first dose must be negative for female patients of childbearing potential.
  • Understand and voluntarily sign informed consent form.

Exclusion Criteria:

  • Patients co-infected with active hepatitis A, hepatitis C, hepatitis D, hepatitis E or HIV.
  • Patients who have previously received interferon therapy.
  • Alpha-fetoprotein greater than 100 ng/mL at screening, or liver imaging suggestive of liver tumor.
  • Decompensated liver disease (Child-Pugh score ≥ 5).
  • Pregnant or lactating women or patients planning to become pregnant or cannot to take contraception during the study.
  • Neutrophil count < 1.5 x 109/L, platelet count < 90 x 109 cells/L, or Creatinine 1.5 times higher than the upper limit of normal.
  • Patients with severe psychiatric history, particularly depression.
  • History of immune-mediated disease or levels of autoimmune antibodies markedly elevated.
  • Patients with severe diseases in major organ, such as heart, lung, kidney, brain, blood, etc., and patients with malignancies.
  • Patients with poorly controlled diabetes, hypertension, and thyroid disease.
  • Patients with history of severe retinopathy or other evidence of retinopathy.
  • Patient who ever received organ transplantation, or planning to receive organ transplantation.
  • Patients who are allergic to interferon or any of its ingredients.
  • Other circumstances that the investigator deems inappropriate to participate in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combined treatment group
Peginterferon alfa-2b Injection combined Nucleos (t) ide Analogue therapy
Drug: Peginterferon alfa-2b Injection, Nucleos (t) ide Analogue

1.Peginterferon alfa-2b injection: 180μg, subcutaneously inject, once a week, from week 1 to Week 48.

2, NAs: Dose please follow the approved dosage, once daily, from the first day until when discontinuation is indicated.

NAs Discontinuation Criteria: A total course of treatment is recommended for at least 4 years, and discontinuation may be considered if HBV DNA is below the lower limit of detection, Alanine aminotransferase renormalization, and HBeAg serological conversion, and remain unchanged (test every 6 months) during a consolidation therapy for at least 3 years. However, a prolonged course of treatment may reduce relapse.
Active Comparator: Monotherapy group
Nucleos (t) ide Analogue monotherapy
Drug: Nucleos(t)ide analogue

NAs: Dose please follow the approved dosage, once daily, from the first day until when discontinuation is indicated.

NAs Discontinuation Criteria: A total course of treatment is recommended for at least 4 years, and discontinuation may be considered if HBV DNA is below the lower limit of detection, Alanine aminotransferase renormalization, and HBeAg serological conversion, and remain unchanged (test every 6 months) during a consolidation therapy for at least 3 years. However, a prolonged course of treatment may reduce relapse.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change of HBsAg level compared to baseline
Time Frame: week 48 of treatment
week 48 of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients with HBsAg clearance
Time Frame: At week 48 of treatment and 5 years of follow up
At week 48 of treatment and 5 years of follow up
Proportion of patients with HBsAg seroconversion
Time Frame: At week 48 of treatment and 5 years of follow up
At week 48 of treatment and 5 years of follow up
Incidence of liver cirrhosis and hepatocellular carcinoma
Time Frame: At week 48 of treatment and 5 years of follow up
At week 48 of treatment and 5 years of follow up
Proportion of patients with change of liver stiffness measurement (LSM)
Time Frame: At week 48 of treatment and 5 years of follow up
At week 48 of treatment and 5 years of follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Qing XIe

Investigators

  • Principal Investigator: Qing Xie, Ruijin Hospital, Shanghai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 3, 2019

Primary Completion (Estimated)

August 1, 2023

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

March 15, 2020

First Submitted That Met QC Criteria

January 2, 2023

First Posted (Actual)

January 4, 2023

Study Record Updates

Last Update Posted (Actual)

May 25, 2023

Last Update Submitted That Met QC Criteria

May 23, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PARADISE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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