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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug Entecavir
  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.
• Drug Entecavir + Pegylated interferon α-2b
  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.

Primary outcome measures

• The rate of functional cure [Time frame: At 24 weeks after treatment cessation.]

Secondary outcome measures (8)

• The rate of HBV DNA undetectable [Time frame: At week 24, 48, 72, 96, 120 of the study.]
• The rate of HBeAg loss [Time frame: At week 24, 48, 72, 96, 120 of the study.]
• The rate of HBsAg loss [Time frame: At week 24, 48, 72, 96, 120 of the study.]
• The rate of alanine aminotransferase elevation or flare [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 [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 growth suppression [Time frame: At week 24, 48, 60, 72, 84, 96, 108, 120 of the study.]
• The rate of thyroid dysfunction [Time frame: At week 72, 96, and 120 of the study.]
• Any other adverse event [Time frame: At any time during study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.]

Eligibility criteria

Inclusion criteria

• Aged 3-6 (more than 3 but less than 7) years;
• With chronic HBV infection;
• HBeAg-positive;
• HBV DNA >1.0×10⁷ IU/mL;
• Normal upper abdominal ultrasound;
• 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

• Previous antiviral treatment for chronic HBV infection;
• Coinfection with hepatitis C, D, E, human immunodeficiency virus (HIV), Epstein-Barr virus, or cytomegalovirus;
• Previous or current evidence of hepatocellular carcinoma or cirrhosis;
• Coexistence of any other liver diseases such as autoimmune hepatitis, drug-induced liver injury or Wilson's disease;
• Coexistence of systemic/other organ disorders (for example with evidence of thyroid disorders);
• Hemoglobin level <100 g/L.
• Absolute neutrophil count <1.0×10⁹/L;
• Platelet count <125×10⁹/L;
• Total bilirubin >1 ULN, i.e., 17.1 μmol/L;
• Albumin level <35 g/L;
• 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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07345624 · 2025-KY-1632-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗