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NCT Number: NCT06923280

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

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).

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Key information

Conditions

Hepatitis B, Chronic Blood-Borne Infections Chronic Disease Communicable Diseases DNA Virus Infections Digestive System Diseases Disease Attributes Hepadnaviridae Infections Hepatitis Hepatitis B Hepatitis, Chronic Hepatitis, Viral, Human Infections Liver Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Virus Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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: 0.05-500 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 criteria

  • 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).

Treatment and study plan

Pegylated Interferon-alpha (IFN)

Drug

pegylated interferon-alpha 180 μg once weekly for 24 weeks

Primary outcomes

  1. HBV DNA and HBsAg undetectable with/without anti-HBs

    Time frame: 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.

Secondary outcomes

  1. HBV DNA and HBsAg undetectable with/without anti-HBs during the study

    Time frame: Weeks 24, 48, and 96

    Proportion of patients achieving HBV DNA <20 IU/mL, HBsAg <0.05 IU/mL (with or without anti-HBs), and normal liver biochemistry at Weeks 24, 48, and 96.

  2. HBV DNA and HBsAg undetectable during the study

    Time frame: Weeks 24, 48, 72, and 96

    Proportion of patients achieving HBsAg <0.05 IU/mL and HBV DNA <20 IU/mL at Weeks 24, 48, 72, and 96.

  3. HBsAg level

    Time frame: Weeks 24, 48, 72, and 96

    HBsAg levels in each group at Weeks 24, 48, 72, and 96

  4. HBsAg decline from baseline

    Time frame: Weeks 24, 48, 72, and 96

    Magnitude of HBsAg decline from baseline in each group at Weeks 24, 48, 72, and 96

  5. HBsAg seroclearance

    Time frame: Weeks 24, 48, 72, and 96

    HBsAg seroclearance rate (HBsAg <0.05 IU/mL) in each group at Weeks 24, 48, 72, and 96

  6. HBsAg seroconversion

    Time frame: Weeks 24, 48, 72, and 96

    HBsAg seroconversion rate (anti-HBs ≥10 mIU/mL) in each group at Weeks 24, 48, 72, and 96

  7. HBeAg seroclearance

    Time frame: Weeks 24, 48, 72, and 96

    HBeAg seroclearance rate in baseline HBeAg-positive patients at Weeks 24, 48, 72, and 96

  8. HBeAg seroconversion

    Time frame: Weeks 24, 48, 72, and 96

    HBeAg seroconversion rate (anti-HBe positivity) in baseline HBeAg-positive patients at Weeks 24, 48, 72, and 96

  9. HBV DNA level

    Time frame: Weeks 24, 48, 72, and 96

    HBV DNA levels in each group at Weeks 24, 48, 72, and 96

  10. HBV DNA decline from baseline

    Time frame: Weeks 24, 48, 72, and 96

    Magnitude of HBV DNA decline from baseline in each group at Weeks 24, 48, 72, and 96

  11. HBV DNA undetectabe

    Time frame: Weeks 24, 48, 72, and 96

    HBV DNA undetectability rate (<20 IU/mL) in baseline HBV DNA-positive patients at Weeks 24, 48, 72, and 96

  12. ALT levels

    Time frame: Weeks 24, 48, 72, and 96

    ALT levels in each group at Weeks 24, 48, 72, and 96

  13. ALT normalization

    Time frame: Weeks 24, 48, 72, and 96

    ALT normalization rate (≤upper limit of normal [ULN]) in each group at Weeks 24, 48, 72, and 96

  14. ALT levels from baseline

    Time frame: Weeks 24, 48, 72, and 96

    Change in ALT levels from baseline in each group at Weeks 24, 48, 72, and 96

  15. saftey

    Time frame: Weeks 24, 48, 72, and 96

    Incidence of adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs) during the study, including findings from Physical examinations, Laboratory tests, Hematology, Urinalysis, Blood biochemistry, Coagulation profile

Other outcomes

  1. HBV RNA

    Time frame: Weeks 24, 48, 72, and 96

    HBV pregenomic RNA (pgRNA) levels in each group at Weeks 24, 48, 72, and 96.

  2. HBcrAg

    Time frame: Weeks 24, 48, 72, and 96

    HBV core-related antigen (HBcrAg) levels in each group at Weeks 24, 48, 72, and 96

  3. HBsAg-specific T-cell and B-cell

    Time frame: during the study

    Longitudinal changes in HBsAg-specific T-cell and B-cell responses during the study

  4. HBV quasispecies variations

    Time frame: Weeks 24, 48, 72, and 96

    Characterize HBV quasispecies variations

  5. proteomic profiles

    Time frame: Weeks 24, 48, 72, and 96

    Assess longitudinal changes in proteomic profiles during the study

  6. baseline GWAS

    Time frame: baseline

    Analyze baseline genomic characteristics and GWAS (Genome-Wide Association Study) data of patients

Study contacts

Contact information is provided by the study sponsor or research team.

Wenghong Zhang, MD

CONTACT

[email protected]

13801844344

Sponsors and collaborators

Lead sponsor

Huashan Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Apr 11, 2025
Registry last updated
Apr 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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