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

Not Applicable

Not yet recruiting

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Pegylated Interferon-alpha (IFN)

• Registration Number: NCT06923280
• Lead Sponsor: Huashan Hospital

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-03
• Study First Submitted QC: 2025-04-09
• Last Update Submitted: 2025-04-09
• Study First Posted: 2025-04-11
• Last Update Posted: 2025-04-11
• Study Start: 2025-05-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-05-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
A：Immediate PEG-IFNα Induction	Pegylated Interferon-alpha (IFN)	Receive PEG-IFNα for 24 weeks, followed by 24-week treatment-free follow-up
B: Deferred PEG-IFNα Initiation	Pegylated Interferon-alpha (IFN)	Undergo 24-week observation, then receive PEG-IFNα for 24 weeks

Primary Outcome Measures

Name	Time	Method
HBV DNA and HBsAg undetectable with/without anti-HBs	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 Outcome Measures

Name	Time	Method
HBV DNA and HBsAg undetectable with/without anti-HBs during the study	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.
HBV DNA and HBsAg undetectable during the study	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.
HBsAg level	Weeks 24, 48, 72, and 96	HBsAg levels in each group at Weeks 24, 48, 72, and 96
HBsAg decline from baseline	Weeks 24, 48, 72, and 96	Magnitude of HBsAg decline from baseline in each group at Weeks 24, 48, 72, and 96
HBsAg seroclearance	Weeks 24, 48, 72, and 96	HBsAg seroclearance rate (HBsAg \<0.05 IU/mL) in each group at Weeks 24, 48, 72, and 96
HBsAg seroconversion	Weeks 24, 48, 72, and 96	HBsAg seroconversion rate (anti-HBs ≥10 mIU/mL) in each group at Weeks 24, 48, 72, and 96
HBeAg seroclearance	Weeks 24, 48, 72, and 96	HBeAg seroclearance rate in baseline HBeAg-positive patients at Weeks 24, 48, 72, and 96
HBeAg seroconversion	Weeks 24, 48, 72, and 96	HBeAg seroconversion rate (anti-HBe positivity) in baseline HBeAg-positive patients at Weeks 24, 48, 72, and 96
HBV DNA level	Weeks 24, 48, 72, and 96	HBV DNA levels in each group at Weeks 24, 48, 72, and 96
HBV DNA decline from baseline	Weeks 24, 48, 72, and 96	Magnitude of HBV DNA decline from baseline in each group at Weeks 24, 48, 72, and 96
HBV DNA undetectabe	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
ALT levels	Weeks 24, 48, 72, and 96	ALT levels in each group at Weeks 24, 48, 72, and 96
ALT normalization	Weeks 24, 48, 72, and 96	ALT normalization rate (≤upper limit of normal \[ULN\]) in each group at Weeks 24, 48, 72, and 96
ALT levels from baseline	Weeks 24, 48, 72, and 96	Change in ALT levels from baseline in each group at Weeks 24, 48, 72, and 96
saftey	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

Trial Locations

Locations (1)

Huashan Hospita; 🇨🇳 Shanghai, China