A Study on the Pursuit of Sustained Clearance of HBsAg in Chronic Hepatitis B(CHB) Patients With Previous Interferon Treatment Using Pegylated Interferon Alpha

Official title

A Prospective, Non-Randomized, Multicenter Study of Peginterferon Alfa for Pursuing Sustained Hepatitis B Surface Antigen(HBsAg) Clearance in Interferon-Pretreated Patients With Chronic Hepatitis B

Overview

This is a real-world, prospective, multicenter, non-randomized, controlled study. It aims to investigate the efficacy and safety of pegylated interferon α-2b (PEG IFN α-2b) monotherapy versus its combination with nucleos(t)ide analogs (NAs) regarding hepatitis B surface antigen (HBsAg) clearance in interferon-experienced patients with chronic hepatitis B (CHB). Subjects will receive either interferon-based therapy or NAs monotherapy based on their personal willingness and physicians' professional recommendations, with a uniform 48-week treatment course for all enrolled patients.

Interventions

• Drug PEG IFNα-2b monotherapy or combination therapy with NAs
  Peginterferon α-2b injection, 180mcg, s.c, once a week, for 48 weeks.If HBV DNA is below the lower limit of detection at baseline (highly sensitive assay is recommended), PEG IFNα-2b monotherapy will be administered.
• Drug NAs monotherapy group
  Peginterferon α-2b injection, 180mcg, s.c, once a week, for 48 weeks.If HBV DNA is below the lower limit of detection at baseline (highly sensitive assay is recommended), PEG IFNα-2b monotherapy will be administered.

Primary outcome measures

• Percentage of subjects with undetectable HBsAg [Time frame: Week 48]
• Percentage of subjects with undetectable HBV DNA [Time frame: Week 48]

Secondary outcome measures (8)

• Number of patients with a decrease in HBV DNA from baseline [Time frame: Week 1-48]
• Proportion of subjects with HBV DNA below the lower limit of detection [Time frame: Week 1-48]
• Number of patients with a decrease in HBsAg from baseline [Time frame: Week 1-48]
• Proportion of HBsAg seroclearance [Time frame: Week 1-48]
• Proportion of HBsAg seroconversion [Time frame: Week 1-48]
• Proportion of HBeAg seroclearance [Time frame: Week 1-48]
• Proportion of HBeAg seroconversion [Time frame: Week 1-48]
• Serious adverse events [Time frame: Week 1-48]

Eligibility criteria

Inclusion criteria

• • Voluntary participation and ability to understand and provide written informed consent.

• Age 18-65 years (inclusive), either gender.
• Documented HBsAg positivity for at least 6 months, or other evidence confirming chronic hepatitis B (CHB).
• Prior interferon therapy before enrollment (treatment discontinuation ≥ 3 months), with HBsAg level at the end of prior treatment reduced by ≥ 50% from baseline.
• HBsAg ≤ 500 IU/mL at screening, and HBsAg rebound at screening not exceeding 50% of the baseline HBsAg level during the first-round interferon therapy.
• Negative pregnancy test within 24 hours prior to the first dose (for women of childbearing potential); all subjects (male and female) must use effective contraceptive measures during the study.

Exclusion criteria

• • Pregnant or lactating women, or subjects with a pregnancy plan during the study period.

• Subjects with neuropsychiatric disorders, in particular a history of depression, anxiety, mania, schizophrenia, or a family history of psychiatric disorders (especially a history of depression or depressive tendency).
• Concurrent active infection with hepatitis A, hepatitis C, hepatitis E and/or HIV, or chronic liver disease due to other causes (e.g., alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease, etc.).
• Evidence of acute severe liver damage: e.g., ALT > 10 × ULN, or marked ALT elevation accompanied by significant hyperbilirubinemia.
• Evidence of decompensated liver disease: e.g., ascites, esophagogastric variceal bleeding, sepsis, hepatic encephalopathy, hepatorenal syndrome, etc.; or prior evidence of decompensated cirrhosis.
• Evidence of hepatocellular carcinoma (HCC), or AFP > 1 × ULN.
• Renal diseases: acute or chronic nephritis, renal insufficiency, nephrotic syndrome, etc.; or serum creatinine > 1 × ULN at screening.
• Neutrophil count < 1.5 × 10⁹/L, platelet count < 90 × 10⁹/L, or serum phosphorus < 0.8 mmol/L during the screening period.
• Autoimmune diseases (e.g., psoriasis, systemic lupus erythematosus, etc.), endocrine disorders (e.g., thyroid diseases, diabetes, etc.), hypertension poorly controlled by prescription medications (blood pressure ≥ 140/90 mmHg), a history of severe heart disease (especially poorly controlled within 6 months), severe retinopathy or other serious ophthalmologic diseases, or other organic lesions or dysfunction of vital organs.
• Subjects planning to undergo or having previously undergone organ transplantation.
• Subjects with hypersensitivity to the investigational product or its excipients, or meeting any contraindication listed in the prescribing information of the investigational product.
• Other conditions deemed inappropriate for enrollment by the investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

China · 1 center

• Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT07537387 · Leading Study2.0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗