NCT06923280

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:

  • 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).

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
26mo left

Started May 2025

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress33%
May 2025May 2028

First Submitted

Initial submission to the registry

April 3, 2025

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 11, 2025

Completed
20 days until next milestone

Study Start

First participant enrolled

May 1, 2025

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 31, 2028

Last Updated

April 11, 2025

Status Verified

April 1, 2025

Enrollment Period

2.7 years

First QC Date

April 3, 2025

Last Update Submit

April 9, 2025

Conditions

Hepatitis B, Chronic

Outcome Measures

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.

    week 72

Secondary Outcomes (15)

  • HBV DNA and HBsAg undetectable with/without anti-HBs during the study

    Weeks 24, 48, and 96

  • HBV DNA and HBsAg undetectable during the study

    Weeks 24, 48, 72, and 96

  • HBsAg level

    Weeks 24, 48, 72, and 96

  • HBsAg decline from baseline

    Weeks 24, 48, 72, and 96

  • HBsAg seroclearance

    Weeks 24, 48, 72, and 96

  • +10 more secondary outcomes

Other Outcomes (6)

  • HBV RNA

    Weeks 24, 48, 72, and 96

  • HBcrAg

    Weeks 24, 48, 72, and 96

  • HBsAg-specific T-cell and B-cell

    during the study

  • +3 more other outcomes

Study Arms (2)

A：Immediate PEG-IFNα Induction

EXPERIMENTAL

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

Drug: Pegylated Interferon-alpha (IFN)

B: Deferred PEG-IFNα Initiation

EXPERIMENTAL

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

Drug: Pegylated Interferon-alpha (IFN)

Interventions

Pegylated Interferon-alpha (IFN)DRUG

pegylated interferon-alpha 180 μg once weekly for 24 weeks

A：Immediate PEG-IFNα InductionB: Deferred PEG-IFNα Initiation

Eligibility Criteria

Age18 Years - 80 Years
Sexall(Gender-based eligibility)
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Huashan Hospita

Shanghai, China, China

Location

Related Publications (5)

  • Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.

    PMID: 24915612BACKGROUND

  • Yuen MF, Lim YS, Yoon KT, Lim TH, Heo J, Tangkijvanich P, Tak WY, Thanawala V, Cloutier D, Mao S, Arizpe A, Cathcart AL, Gupta SV, Hwang C, Gane E. VIR-2218 (elebsiran) plus pegylated interferon-alfa-2a in participants with chronic hepatitis B virus infection: a phase 2 study. Lancet Gastroenterol Hepatol. 2024 Dec;9(12):1121-1132. doi: 10.1016/S2468-1253(24)00237-1. Epub 2024 Oct 8.

    PMID: 39389081BACKGROUND

  • Mak LY, Wooddell CI, Lenz O, Schluep T, Hamilton J, Davis HL, Mao X, Seto WK, Biermer M, Yuen MF. Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989. Gut. 2025 Feb 6;74(3):440-450. doi: 10.1136/gutjnl-2024-333026.

    PMID: 39266050BACKGROUND

  • Buti M, Heo J, Tanaka Y, Andreone P, Atsukawa M, Cabezas J, Chak E, Coffin CS, Fujiwara K, Gankina N, Gordon SC, Janczewska E, Komori A, Lampertico P, McPherson S, Morozov V, Plesniak R, Poulin S, Ryan P, Sagalova O, Sheng G, Voloshina N, Xie Q, Yim HJ, Dixon S, Paff M, Felton L, Lee M, Greene T, Lim J, Lakshminarayanan D, McGonagle G, Plein H, Youssef AS, Elston R, Kendrick S, Theodore D. Sequential Peg-IFN after bepirovirsen may reduce post-treatment relapse in chronic hepatitis B. J Hepatol. 2025 Feb;82(2):222-234. doi: 10.1016/j.jhep.2024.08.010. Epub 2024 Aug 29.

    PMID: 39214467BACKGROUND

  • Yuen MF, Lim SG, Plesniak R, Tsuji K, Janssen HLA, Pojoga C, Gadano A, Popescu CP, Stepanova T, Asselah T, Diaconescu G, Yim HJ, Heo J, Janczewska E, Wong A, Idriz N, Imamura M, Rizzardini G, Takaguchi K, Andreone P, Arbune M, Hou J, Park SJ, Vata A, Cremer J, Elston R, Lukic T, Quinn G, Maynard L, Kendrick S, Plein H, Campbell F, Paff M, Theodore D; B-Clear Study Group. Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection. N Engl J Med. 2022 Nov 24;387(21):1957-1968. doi: 10.1056/NEJMoa2210027. Epub 2022 Nov 8.

    PMID: 36346079BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Wenghong Zhang, MD

    Huashan Hospital

    PRINCIPAL INVESTIGATOR

  • Jiming Zhang, MD

    Huashan Hospital

    PRINCIPAL INVESTIGATOR

  • Yuxian Huang, MD

    Huashan Hospital

    PRINCIPAL INVESTIGATOR

  • Feng Sun, MD

    Huashan Hospital

    STUDY CHAIR

  • Chao Qiu

    Huashan Hospital

    PRINCIPAL INVESTIGATOR

  • Chen Chen, MD

    Huashan Hospital

    STUDY DIRECTOR

  • Qiran Zhang, MD

    Huashan Hospital

    STUDY DIRECTOR

Central Study Contacts

Wenghong Zhang, MD

CONTACT

13801844344zhangwenhong@fudan.edu.cn

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Division of Infectious Diseases

Study Record Dates

First Submitted

April 3, 2025

First Posted

April 11, 2025

Study Start

May 1, 2025

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

May 31, 2028

Last Updated

April 11, 2025

Record last verified: 2025-04

Locations

CN(1)