Clinical trial NCT06923280: Sequential PEG-IFN for HBV After Ending RNA-targeted Regimens
Official 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Hepatitis B, Chronic
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2025-04-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


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).

Primary outcomes:
measure: HBV DNA and HBsAg undetectable with/without anti-HBs
timeFrame: week 72
Secondary outcomes:
measure: HBV DNA and HBsAg undetectable with/without anti-HBs during the study
timeFrame: Weeks 24, 48, and 96
measure: HBV DNA and HBsAg undetectable during the study
timeFrame: Weeks 24, 48, 72, and 96
measure: HBsAg level
timeFrame: Weeks 24, 48, 72, and 96
measure: HBsAg decline from baseline
timeFrame: Weeks 24, 48, 72, and 96
measure: HBsAg seroclearance
timeFrame: Weeks 24, 48, 72, and 96
measure: HBsAg seroconversion
timeFrame: Weeks 24, 48, 72, and 96
measure: HBeAg seroclearance
timeFrame: Weeks 24, 48, 72, and 96
measure: HBeAg seroconversion
timeFrame: Weeks 24, 48, 72, and 96
measure: HBV DNA level
timeFrame: Weeks 24, 48, 72, and 96
measure: HBV DNA decline from baseline
timeFrame: Weeks 24, 48, 72, and 96
measure: HBV DNA undetectabe
timeFrame: Weeks 24, 48, 72, and 96
measure: ALT levels
timeFrame: Weeks 24, 48, 72, and 96
measure: ALT normalization
timeFrame: Weeks 24, 48, 72, and 96
measure: ALT levels from baseline
timeFrame: Weeks 24, 48, 72, and 96
measure: saftey
timeFrame: Weeks 24, 48, 72, and 96
Other outcomes:
measure: HBV RNA
timeFrame: Weeks 24, 48, 72, and 96
measure: HBcrAg
timeFrame: Weeks 24, 48, 72, and 96
measure: HBsAg-specific T-cell and B-cell
timeFrame: during the study
measure: HBV quasispecies variations
timeFrame: Weeks 24, 48, 72, and 96
measure: proteomic profiles
timeFrame: Weeks 24, 48, 72, and 96
measure: baseline GWAS
timeFrame: baseline
Locations:
city: Shanghai
country: China
facility: Huashan Hospita
Study officials:
affiliation: Huashan Hospital
name: Wenghong Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Jiming Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Yuxian Huang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Feng Sun, MD
role: STUDY_CHAIR
affiliation: Huashan Hospital
name: Chao Qiu
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Chen Chen, MD
role: STUDY_DIRECTOR
affiliation: Huashan Hospital
name: Qiran Zhang, MD
role: STUDY_DIRECTOR
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