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

NCT ID: NCT06923280

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-01
• Study Completion Date: 2028-05-31

Brief 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).

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A：Immediate PEG-IFNα Induction

Receive PEG-IFNα for 24 weeks, followed by 24-week treatment-free follow-up

Group Type: EXPERIMENTAL

Pegylated Interferon-alpha (IFN)

Intervention Type: DRUG

pegylated interferon-alpha 180 μg once weekly for 24 weeks

B: Deferred PEG-IFNα Initiation

Undergo 24-week observation, then receive PEG-IFNα for 24 weeks

Group Type: EXPERIMENTAL

Pegylated Interferon-alpha (IFN)

Intervention Type: DRUG

pegylated interferon-alpha 180 μg once weekly for 24 weeks

Interventions

Pegylated Interferon-alpha (IFN)

pegylated interferon-alpha 180 μg once weekly for 24 weeks

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Huashan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wen-hong Zhang

Director of Division of Infectious Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wenghong Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Jiming Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Yuxian Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Feng Sun, MD

Role: STUDY_CHAIR

Huashan Hospital

Chao Qiu

Role: PRINCIPAL_INVESTIGATOR

Huashan Hospital

Chen Chen, MD

Role: STUDY_DIRECTOR

Huashan Hospital

Qiran Zhang, MD

Role: STUDY_DIRECTOR

Huashan Hospital

Locations

Huashan Hospita

Shanghai, China, China

Countries

China

Central Contacts

Wenghong Zhang, MD

Role: CONTACT

zhangwenhong@fudan.edu.cn

13801844344

Facility Contacts

Wenhong Zhang, Professor

Role: primary

zhangwenhong@fudan.edu.cn

13801844344

Feng Sun, Doctor

Role: backup

aaronsf1125@126.com

References

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Other Identifiers

SPHERE

Identifier Type: -

Identifier Source: org_study_id