NCT06923280招募中不适用
Efficacy and Safety of Pegylated Interferon Therapy in Chronic Hepatitis B Patients After Discontinuation of Antisense Oligonucleotide or Small Interfering RNA: A Prospective, Adaptive, Open-label, Randomized Controlled Study
干预措施
相关药物
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 3
- 主要终点
- HBV DNA and HBsAg undetectable with/without anti-HBs
研究概览
简要总结
The goal of this clinical trial is to compare sequential PEG-IFNα therapy strategies in chronic hepatitis B (CHB) patients previously treated with ASO/siRNA. The main questions it aims to answer are:
- Does sequential PEG-IFNα therapy (vs. deferred/no treatment) improve HBsAg clearance rates?
- What are the HBsAg clearance and relapse rates after 24 weeks of PEG-IFNα therapy?
- Is intermittent PEG-IFNα therapy as effective and safe as continuous therapy?
Researchers will compare:
• Group A (immediate 24-week PEG-IFNα + 24-week follow-up) vs. Group B (24-week observation + 24-week PEG-IFNα) in Phase 1 to see if sequential PEG-IFNα therapy will improve HBsAg loss rate .
Researchers will describe:
- The response rate of IFN treatment in non-responders (HBsAg-positive) in Phase 2.
- The relaspe rate of responders (HBsAg-negative).
Participants will:
Phase 1 (0-48 weeks):
- Group A: Receive PEG-IFNα for 24 weeks, followed by 24-week treatment-free follow-up.
- Group B: Undergo 24-week observation, then receive PEG-IFNα for 24 weeks.
Phase 2 (48-96 weeks):
- HBsAg-positive at week 48 patients either from group A or group B : Receive 24-week PEG-IFNα therapy, followed by 24-week follow-up.
- HBsAg-negative at week 48 patients either from group A or group B: Enter 24-week follow-up without treatment.
All participants will undergo:
• HBsAg quantification, HBV DNA, liver function, and safety monitoring (every 12 weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •Chronic HBV infection (documented HBsAg positivity for >6 months).
- •Prior participation in ASO or siRNA clinical trials:
- •Received ≥1 dose of ASO/siRNA (or matched placebo, if applicable).
- •Achieved ≥1 log10 IU/mL HBsAg decline from baseline during prior therapy.
- •Discontinued ASO/siRNA therapy before screening.
- •Screening HBsAg: 1-500 IU/mL.
- •No prior interferon (IFN) therapy within 6 months before enrollment.
- •Willingness to comply with study-related treatments, tests, and procedures.
- •Commitment to contraception during the study.
- •Voluntary participation with signed informed consent.
排除标准
- •Decompensated cirrhosis or hepatic malignancy (evidenced by imaging or histology within 6 months before/during screening).
- •Elevated AFP: Screening AFP >100 ng/mL; AFP 20-100 ng/mL with imaging-confirmed hepatocellular carcinoma (ultrasound/CT/MRI).
- •Coinfection with hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV), or human immunodeficiency virus (HIV).
- •Recent immunomodulatory therapy: Systemic corticosteroids, thymosin, or other potent immunomodulators for >2 weeks within 6 months before enrollment.
- •Pregnancy, lactation, or plans for pregnancy during the study.
- •Autoimmune hepatitis.
- •Active autoimmune diseases (e.g., psoriasis, systemic lupus erythematosus).
- •Uncontrolled cardiovascular disease (e.g., unstable angina, myocardial infarction within 6 months).
- •Poorly controlled endocrine disorders (e.g., diabetes mellitus, thyroid dysfunction).
- •Severe psychiatric disorders: History of depression, anxiety, bipolar disorder, schizophrenia, or family history of psychiatric conditions (especially depression).
- •Substance abuse: Alcohol (>40 g/day for males; >20 g/day for females) or Illicit drug use.
- •Severe retinopathy or ophthalmologic disorders.
- •Renal diseases: Chronic nephritis, renal insufficiency, nephrotic syndrome.
- •Major organ dysfunction (e.g., heart, lung, pancreas).
- •Organ transplant recipients or candidates.
- •Hypersensitivity to interferon or excipients.
- •Concurrent participation in other HBV-related interventional trials.
- •Other conditions deemed unsuitable by investigators (e.g., non-compliance risk).
研究组 & 干预措施
A：Immediate PEG-IFNα Induction
Experimental
Receive PEG-IFNα for 24 weeks, followed by 24-week treatment-free follow-up
干预措施: Pegylated Interferon-alpha (IFN) (Drug)
B: Deferred PEG-IFNα Initiation
Experimental
Undergo 24-week observation, then receive PEG-IFNα for 24 weeks
干预措施: Pegylated Interferon-alpha (IFN) (Drug)
结局指标
主要结局
HBV DNA and HBsAg undetectable with/without anti-HBs
时间窗: week 72
Proportion of patients achieving HBV DNA below the lower limit of quantification (LLOQ; \<20 IU/mL), HBsAg undetectable (\<0.05 IU/mL) (with or without anti-HBs seroconversion), and normal liver biochemical indices at Week 72.
次要结局
- HBV DNA and HBsAg undetectable with/without anti-HBs during the study(Weeks 24, 48, and 96)
- HBV DNA and HBsAg undetectable during the study(Weeks 24, 48, 72, and 96)
- HBsAg level(Weeks 24, 48, 72, and 96)
- HBsAg decline from baseline(Weeks 24, 48, 72, and 96)
- HBsAg seroclearance(Weeks 24, 48, 72, and 96)
- HBsAg seroconversion(Weeks 24, 48, 72, and 96)
- HBeAg seroclearance(Weeks 24, 48, 72, and 96)
- HBeAg seroconversion(Weeks 24, 48, 72, and 96)
- HBV DNA level(Weeks 24, 48, 72, and 96)
- HBV DNA decline from baseline(Weeks 24, 48, 72, and 96)
- HBV DNA undetectabe(Weeks 24, 48, 72, and 96)
- ALT levels(Weeks 24, 48, 72, and 96)
- ALT normalization(Weeks 24, 48, 72, and 96)
- ALT levels from baseline(Weeks 24, 48, 72, and 96)
- saftey(Weeks 24, 48, 72, and 96)
- Percentage of patients who achieved functional cure(24 weeks off Peg-IFNα treatment)
研究者
Wen-hong Zhang
Director of Division of Infectious Diseases
Huashan Hospital
研究点 (3)
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