A Non-randomized Controlled, Prospective, Real-world Study to Evaluate the Efficacy and Safety of Pegylated Interferon Alpha-2β in Patients With Hepatitis B-related Hepatocellular Carcinoma After Radical Resection
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 156
- 试验地点
- 4
- 主要终点
- Concentration of Hepatitis B Surface Antigen (Hepatitis B Surface Antigen, HBsAg)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
NAs alone
Patients receive first-line nucleos(t)ide analogues (TDF/TAF/TMF) alone
干预措施: TMF (Drug)
Peginterferon alfa-2b combined with NAs
Patients receive peginterferon alfa-2b (Pegintron®) combined with first-line nucleos(t)ide analogues (TDF/TAF/TMF)
干预措施: TMF (Drug)
Peginterferon alfa-2b combined with NAs
Patients receive peginterferon alfa-2b (Pegintron®) combined with first-line nucleos(t)ide analogues (TDF/TAF/TMF)
干预措施: TDF (Drug)
NAs alone
Patients receive first-line nucleos(t)ide analogues (TDF/TAF/TMF) alone
干预措施: TDF (Drug)
Peginterferon alfa-2b combined with NAs
Patients receive peginterferon alfa-2b (Pegintron®) combined with first-line nucleos(t)ide analogues (TDF/TAF/TMF)
干预措施: Peginterferon alfa-2b (Drug)
NAs alone
Patients receive first-line nucleos(t)ide analogues (TDF/TAF/TMF) alone
干预措施: TAF (Drug)
Peginterferon alfa-2b combined with NAs
Patients receive peginterferon alfa-2b (Pegintron®) combined with first-line nucleos(t)ide analogues (TDF/TAF/TMF)
干预措施: TAF (Drug)
结局指标
主要结局
Concentration of Hepatitis B Surface Antigen (Hepatitis B Surface Antigen, HBsAg)
时间窗: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Serum HBsAg concentration assessed by Chemiluminescent Microparticle Immunoassay (CMIA). Unit: IU/mL
Proportion of patients with HBsAg loss
时间窗: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
Proportion of patients with HBsAg loss (HBsAg \< 0.05 IU/mL) determined by CMIA. Unit: % of patients
Proportion of patients with HBsAg seroconversion
时间窗: Baseline, Weeks 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240
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
次要结局
- Overall survival (OS)(Years 1, 2, 3, 5)
- 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)
- Concentration of Interleukin-2 (IL-2)(Baseline, Week 24, Week 48)
- Concentration of Interleukin-4 (IL-4)(Baseline, Week 24, Week 48)
- Concentration of Interleukin-6 (IL-6)(Baseline, Week 24, Week 48)
- Concentration of Interleukin-10 (IL-10)(Baseline, Week 24, Week 48)
- Concentration of Tumor Necrosis Factor-α (TNF-α)(Baseline, Week 24, Week 48)
- Concentration of Interferon-γ (IFN-γ)(Baseline, Week 24, Week 48)
研究者
Liyun Fu
Chief Physician
Ningbo No.2 Hospital