Sequential PEG-IFN for HBV After Ending RNA-targeted Regimens
ConditionHepatitis B, Chronic
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorHuashan Hospital
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years.
Chronic HBV infection (documented HBsAg positivity for >6 months).
Received ≥1 dose of ASO/siRNA (or matched placebo, if applicable).
Achieved ≥1 log10 IU/mL HBsAg decline from baseline during prior therapy.
Disqualifiers
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.
Trial design
Design model
Crossover
Treatments tested in this trial
Pegylated Interferon-alpha (IFN)
Drugpegylated interferon-alpha 180 μg once weekly for 24 weeks
Treatment groups
72 Participants
are divided into 2 treatment groupsGroup A: A：Immediate PEG-IFNα InductionExperimental treatment 1 intervention
Group B: B: Deferred PEG-IFNα InitiationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
HBV DNA and HBsAg undetectable with/without anti-HBs
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.
Time frame
week 72Secondary outcomes
1
HBV DNA and HBsAg undetectable with/without anti-HBs during the study
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.
Time frame
Weeks 24, 48, and 962
HBV DNA and HBsAg undetectable during the study
Proportion of patients achieving HBsAg \<0.05 IU/mL and HBV DNA \<20 IU/mL at Weeks 24, 48, 72, and 96.
Time frame
Weeks 24, 48, 72, and 963
HBsAg level
HBsAg levels in each group at Weeks 24, 48, 72, and 96
Time frame
Weeks 24, 48, 72, and 964
HBsAg decline from baseline
Magnitude of HBsAg decline from baseline in each group at Weeks 24, 48, 72, and 96
Time frame
Weeks 24, 48, 72, and 96Other outcomes
1
HBV RNA
HBV pregenomic RNA (pgRNA) levels in each group at Weeks 24, 48, 72, and 96.
Time frame
Weeks 24, 48, 72, and 962
HBcrAg
HBV core-related antigen (HBcrAg) levels in each group at Weeks 24, 48, 72, and 96
Time frame
Weeks 24, 48, 72, and 963
HBsAg-specific T-cell and B-cell
Longitudinal changes in HBsAg-specific T-cell and B-cell responses during the study
Time frame
during the study4
HBV quasispecies variations
Characterize HBV quasispecies variations
Time frame
Weeks 24, 48, 72, and 96Sponsors and contacts
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Source ClinicalTrials.gov