Efficacy and Safety of Pegylated Interferon Alpha-2β in Patients With Hepatitis B-related Hepatocellular Carcinoma After Radical Resection

NCT07553767 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: PJ-NBEY-KY-2025-215-01
• Study Type: interventional
• Target: 156
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of peginterferon alfa-2β (Peg-IFN-α-2β) combined with nucleos(t)ide analogues (NAs) in patients aged 18 to 65 years with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after radical resection. The main questions it aims to answer are:

• What are the changes in hepatitis B surface antigen (HBsAg) disappearance rate, HBsAg seroconversion rate, HBsAg decline, and hepatitis B virus deoxyribonucleic acid (HBV DNA) levels during treatment and at the end of treatment?
• What are the 1-year, 2-year, 3-year, and 5-year recurrence-free survival (RFS) and overall survival (OS) of the included patients?
• What are the correlations between changes in HBsAg, T helper 1/T helper 2 (Th1/Th2) subsets, intestinal flora and RFS, OS in these patients? Researchers will compare Peg-IFN-α-2β combined with NAs to NAs alone to see if the combination treatment can improve HBsAg clearance, seroconversion, long-term survival and reduce recurrence in patients after radical resection of hepatitis B-related hepatocellular carcinoma. Participants will:
• Receive either Peg-IFN-α-2β combined with first-line NAs (tenofovir disoproxil fumarate \[TDF\], tenofovir alafenamide fumarate \[TAF\], tenofovir amibufen fumarate \[TMF\]) or first-line NAs alone
• Undergo regular assessments including HBsAg, HBV DNA, liver and renal function, blood routine, thyroid function, autoantibodies, and tumor markers
• Provide stool samples for intestinal flora analysis at specified time points
• Complete long-term survival follow-up for up to 5 years

Conditions

Hepatocellular Carcinoma; HEPATITIS B CHRONIC; Hepatitis B Chronic Infection

Keywords

Peg-IFN-α-2b; hepatitis B; hepatocellular carcinoma; prognosis

Outcome Measures

Primary Outcomes (3)

• Concentration of Hepatitis B Surface Antigen (Hepatitis B Surface Antigen, HBsAg)

  Serum HBsAg concentration assessed by Chemiluminescent Microparticle Immunoassay (CMIA). Unit: IU/mL

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240

• Proportion of patients with HBsAg loss

  Proportion of patients with HBsAg loss (HBsAg \< 0.05 IU/mL) determined by CMIA. Unit: % of patients

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240

• Proportion of patients with HBsAg seroconversion

  Proportion of patients with HBsAg loss (HBsAg \< 0.05 IU/mL) and anti-HBs seropositivity (anti-HBs ≥ 10 mIU/mL) determined by CMIA. Unit: % of patients

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240

Secondary Outcomes (11)

• Concentration of HBV DNA (Hepatitis B Virus Deoxyribonucleic Acid)

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240

• Concentration of Hepatitis B e Antigen (HBeAg)

  Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240

• Composition and diversity of intestinal microbiota

  Baseline, Week 24, Week 48

• Recurrence-Free Survival (RFS)

  Years 1, 2, 3, 5

• Overall survival (OS)

  Years 1, 2, 3, 5

Other Outcomes (36)

• The Levels of Thyroid Stimulating Hormone (TSH)

  Baseline, Weeks 12, 24, 36, 48

• The Levels of Free Triiodothyronine (FT3)

  Baseline, Weeks 12, 24, 36, 48

• The Levels of Free Thyroxine (FT4)

  Baseline, Weeks 12, 24, 36, 48

Study Arms (2)

Peginterferon alfa-2b combined with NAs

EXPERIMENTAL

Patients receive peginterferon alfa-2b (Pegintron®) combined with first-line nucleos(t)ide analogues (TDF/TAF/TMF)

Drug: Peginterferon alfa-2b; Drug: TDF; Drug: TAF; Drug: TMF

NAs alone

ACTIVE COMPARATOR

Patients receive first-line nucleos(t)ide analogues (TDF/TAF/TMF) alone

Drug: TDF; Drug: TAF; Drug: TMF

Interventions

Peginterferon alfa-2b DRUG

Peginterferon alfa-2b injection administered subcutaneously

Peginterferon alfa-2b combined with NAs

TDF DRUG

Tenofovir disoproxil fumarate

NAs alone; Peginterferon alfa-2b combined with NAs

TAF DRUG

Tenofovir alafenamide

NAs alone; Peginterferon alfa-2b combined with NAs

TMF DRUG

Tenofovir amibufenamide

NAs alone; Peginterferon alfa-2b combined with NAs

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 65 years, male or female.
• Confirmed diagnosis of hepatitis B virus-related hepatocellular carcinoma (HCC) by pathology or contrast-enhanced CT/MRI.
• Underwent radical resection or local ablation therapy; CNLC (Chinese Liver Cancer Classification) stage Ia, Ib, or IIa; no residual tumor confirmed by imaging within 1-3 months postoperation.
• HBsAg positive and HBsAg level \< 2000 IU/mL.
• No prior systemic chemotherapy, immunotherapy, or targeted therapy before enrollment.
• Able to provide written informed consent and comply with the follow-up schedule.
• For women of childbearing potential: negative pregnancy test and effective contraception during treatment and for 24 weeks after the last dose.

You may not qualify if:

• Recurrent or metastatic HCC at enrollment.
• Contraindication to peginterferon alfa-2b treatment.
• WBC \< 3.5×10⁹/L or platelet count \< 100×10⁹/L.
• ALT \> 3×ULN or total bilirubin (TBIL) \> 2×ULN.
• Child-Pugh score \> 5 points.
• INR \> 1.5.
• History of organ transplantation or planned transplantation.
• Hypersensitivity to peginterferon alfa-2b or any excipient of the study drug.
• Pregnant or breastfeeding women.
• Participation in another interventional clinical trial.
• History of significant alcoholism or drug abuse.
• Genetic or metabolic liver disease (Wilson disease, hemochromatosis, etc.).
• Coinfection with HAV, HCV, HEV, EBV, CMV , or other viral hepatitis that may interfere with study evaluation.
• Unable to comply with study procedures and follow-up.
• Other conditions deemed inappropriate by the investigator.

Sponsors & Collaborators

• Ningbo No.2 Hospital: lead
• Ningbo Medical Center Lihuili Hospital: collaborator
• Shulan (Hangzhou) Hospital: collaborator
• Ningbo Mingzhou Hospital (Affiliated to Zhejiang University): collaborator

Study Sites (4)

Shulan (Hangzhou) Hospital

Hangzhou, Zhejiang, 310022, China

Location

Ningbo Medical Center Lihuili Hospital

Ningbo, Zhejiang, 315000, China

Location

Ningbo Mingzhou Hospital (Affiliated to Zhejiang University)

Ningbo, Zhejiang, 315000, China

Location

Ningbo No.2 Hospital

Ningbo, Zhejiang, 315000, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis B, Chronic; Hepatitis B

Interventions

peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Liyun Fu

CONTACT

+86 13777966906; nbfly2009@126.com

Mengyuan Hu

CONTACT

+86 17858767819; hmy_helen@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: March 29, 2026
• First Posted: April 28, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): December 31, 2034
• Study Completion (Estimated): December 31, 2035
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)