Entecavir With or Without Pegylated Interferon α-2b in Children Aged 3-6 Years With Immune-Tolerant Chronic Hepatitis B

Efficacy and Safety of Entecavir With or Without Pegylated Interferon α-2b in Children Aged 3 to 6 Years With Immune-Tolerant Chronic Hepatitis B Virus Infection (B-Young-Cure-1): A Multicenter, Open-Label, Randomized Controlled Trial

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.

Inclusion Criteria:

1. Aged 3-6 (more than 3 but less than 7) years;
2. With chronic HBV infection;
3. HBeAg-positive;
4. HBV DNA >1.0×10⁷ IU/mL;
5. Normal upper abdominal ultrasound;
6. ALT <40 U/L, HBsAg positivity, HBeAg positivity, and HBV DNA>1.0×10⁷IU/mL for at least two times, with an interval of 6 months or more.

Exclusion Criteria:

1. Previous antiviral treatment for chronic HBV infection;
2. Coinfection with hepatitis C, D, E, human immunodeficiency virus (HIV), Epstein-Barr virus, or cytomegalovirus;
3. Previous or current evidence of hepatocellular carcinoma or cirrhosis;
4. Coexistence of any other liver diseases such as autoimmune hepatitis, drug-induced liver injury or Wilson's disease;
5. Coexistence of systemic/other organ disorders (for example with evidence of thyroid disorders);
6. Hemoglobin level <100 g/L.
7. Absolute neutrophil count <1.0×10⁹/L;
8. Platelet count <125×10⁹/L;
9. Total bilirubin >1 ULN, i.e., 17.1 μmol/L;
10. Albumin level <35 g/L;
11. Concurrent treatment with other drugs, including but not limited to nephrotoxic drugs, immune modulators, cytotoxic drugs, Chinese traditional medicine or supplements, nonsteroidal anti-inflammatory drugs, or steroids.