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

NCT ID: NCT05671315

Last Updated: 2023-05-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

267 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-03

Study Completion Date

2026-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Hepatitis B Intermediate to High Risk of HCC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Combined treatment group

Peginterferon alfa-2b Injection combined Nucleos (t) ide Analogue therapy

Group Type EXPERIMENTAL

Peginterferon alfa-2b Injection, Nucleos (t) ide Analogue

Intervention Type DRUG

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.

Monotherapy group

Nucleos (t) ide Analogue monotherapy

Group Type ACTIVE_COMPARATOR

Nucleos(t)ide analogue

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Qing XIe

OTHER

Sponsor Role lead

Responsible Party

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Qing XIe

Director of Department of Infectious Disease, Rui Jin Hospital

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Qing Xie

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital, Shanghai

Locations

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The Public Health Clinical Center Of Chengdu

Chengdu, , China

Site Status RECRUITING

The First Affiliated Hospital of USTC Anhui Provincial Hospital

Hefei, , China

Site Status RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, , China

Site Status RECRUITING

Ruijin Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status RECRUITING

Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status RECRUITING

Tongren Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status RECRUITING

The Fifth People's Hospital Of Suzhou

Suzhou, , China

Site Status RECRUITING

Xiamen Hospital of Traditional Chinese Medicin

Xiamen, , China

Site Status RECRUITING

The Tirth Affiliated Hospital Of Xinxiang Medical University

Xinxiang, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Qing Xie, Ph.D

Role: CONTACT

Facility Contacts

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Yilan Zeng

Role: primary

Yi Li

Role: primary

Yuan Guo

Role: primary

Qing Xie

Role: primary

Jie Xu

Role: primary

Qin Zhang

Role: primary

Chuanwu Zhu

Role: primary

Lijuan Ouyang

Role: primary

Weifeng Zhao

Role: primary

References

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Jiang S, Guo S, Huang Y, Xu J, Li Y, Zeng Y, Guo Y, Ouyang L, Zhu C, Zhao W, Zhang Q, Guo Q, Xin H, Xie Q. Interim analysis of the PARADISE study: Benefits of add-on peginterferon-alpha in NA-treated patients with CHB. Antiviral Res. 2024 Jun;226:105892. doi: 10.1016/j.antiviral.2024.105892. Epub 2024 Apr 23.

Reference Type DERIVED
PMID: 38663455 (View on PubMed)

Other Identifiers

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Paradise

Identifier Type: -

Identifier Source: org_study_id

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