RecruitingNot ApplicableNCT06923280

Sequential PEG-IFN for HBV After Ending RNA-targeted Regimens

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

Sponsor

Huashan Hospital

Enrollment

72 participants

Start Date

Aug 25, 2025

Study Type

INTERVENTIONAL

Conditions

Hepatitis B, Chronic

Summary

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: 1. Does sequential PEG-IFNα therapy (vs. deferred/no treatment) improve HBsAg clearance rates? 2. What are the HBsAg clearance and relapse rates after 24 weeks of PEG-IFNα therapy? 3. 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).

Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria11

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.

Exclusion Criteria18

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).