Hepatitis B, Chronic
Conditions
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).
Interventions
pegylated interferon-alpha 180 μg once weekly for 24 weeks
Sponsors
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| baseline GWAS | baseline | Analyze baseline genomic characteristics and GWAS (Genome-Wide Association Study) data of patients |
| HBV RNA | Weeks 24, 48, 72, and 96 | HBV pregenomic RNA (pgRNA) levels in each group at Weeks 24, 48, 72, and 96. |
| HBcrAg | Weeks 24, 48, 72, and 96 | HBV core-related antigen (HBcrAg) levels in each group at Weeks 24, 48, 72, and 96 |
| HBsAg-specific T-cell and B-cell | during the study | Longitudinal changes in HBsAg-specific T-cell and B-cell responses during the study |
| proteomic profiles | Weeks 24, 48, 72, and 96 | Assess longitudinal changes in proteomic profiles during the study |
| HBV quasispecies variations | Weeks 24, 48, 72, and 96 | Characterize HBV quasispecies variations |
Countries
China
Contacts
Primary ContactWenghong Zhang, MD
Outcome results
None listed