This study aims to evaluate the efficacy and safety of entecavir monotherapy versus sequential entecavir plus pegylated interferon α-2b in achieving functional cure in immune-tolerant, HBeAg-positive children aged 3-6 years with chronic hepatitis B virus infection.
This is a multicenter, open-label, randomized controlled, phase 4 trial enrolling 3-6-year-old children with immune-tolerant HBeAg-positive chronic HBV infection. Participants will be randomly assigned in a 1:1 ratio to two treatment arms, both lasting 96 weeks. The ETV group will receive entecavir (ETV) monotherapy throughout the 96-week treatment course (ETV group). The pegylated interferon (Peg-IFN) group will receive ETV for the first 48 weeks, followed by combination therapy with Peg-IFN α-2b for the remaining 48 weeks (ETV plus IFN combination group). The primary endpoint is the functional cure rate at 24 weeks after treatment discontinuation (week 120). The main secondary endpoints include the rates of undetectable HBV DNA, HBeAg loss, and HBsAg loss at week 24, 48, 72, 96, and 120, and rates of alanine aminotransferase elevation or flares (\>5 times of upper limit of normal) and incidence of adverse events at any time during the study. The study will also explore associations between functional cure and baseline or on-treatment parameters. A total of 80 children (40 per group) is required to detect a statistically significant difference between two treatment arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
Receive entecavir onotherapy throughout the 96-week treatment course, the dosage of entecavir is 0.015 mg/kg/day for those weighing between 10 and 30 kg; for those weighing more than 30 kg, the dosage is 0.5 mg/day, oral.
Receive entecavir (with dosing adjusted by body weight: 0.015 mg/kg/day for subjects weighing 10-30 kg, and 0.5 mg/day for those \>30 kg, oral) for the first 48 weeks, followed by combination therapy with pegylated interferon α-2b (104 μg/m², weekly, subcutaneous injection) for the remaining 48 weeks.
The rate of functional cure
Functional cure is defined as the loss of HBsAg to \<0.05 IU/mL and HBeAg clearance, with or without the presence of hepatitis B surface antibody (HBsAb) and hepatitis B e antibody (HBeAb), and undetectable HBV DNA (\<10 IU/mL) at the end of treatment, sustained through 24 weeks post-treatment.
Time frame: At 24 weeks after treatment cessation.
The rate of HBV DNA undetectable
Proportion of participants with HBV DNA undetectable, defined as HBV DNA \<10 IU/mL.
Time frame: At week 24, 48, 72, 96, 120 of the study.
The rate of HBeAg loss
Proportion of participants with HBeAg loss, defined as HBeAg \<0.18 PEIU/mL.
Time frame: At week 24, 48, 72, 96, 120 of the study.
The rate of HBsAg loss
Proportion of participants with HBsAg loss, defined as HBsAg \<0.05 IU/mL.
Time frame: At week 24, 48, 72, 96, 120 of the study.
The rate of alanine aminotransferase elevation or flare
Proportion of participants with alanine aminotransferase elevation (\> 1 time the upper limit of normal, i.e., \>40 U/L) or flare rate, defined as ALT \>5 times the upper limit of normal, i.e., \>200 U/L.
Time frame: At any time during the study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.
The rate of cytopenia rate
Proportion of participants with cytopenia, defined as an absolute neutrophil count \<1.0×10⁹/L and/or a platelet count \<100×10⁹/L.
Time frame: At any time during the study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The rate of growth suppression
Growth suppression rate, defined as height and weight measurements falling below expected levels based on Chinese national standards and World Health Organization anthropometric z-scores for child growth.
Time frame: At week 24, 48, 60, 72, 84, 96, 108, 120 of the study.
The rate of thyroid dysfunction
Proportion of participants with thyroid dysfunction rate, defined as thyroid-stimulating hormone (TSH, normal range 0.27-10 mU/L), free thyroxine (FT4, normal range 10.3-31 pmol/L), or free triiodothyronine (FT3, normal range 3-11.4 pmol/L) levels exceeds the limit of normal or the lower limit of normal .
Time frame: At week 72, 96, and 120 of the study.
Any other adverse event
Incidence of other adverse event at any time during study, including but not limited to flu-like symptoms and signs, rash, and other expected or unexpected adverse event.
Time frame: At any time during study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.