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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Hepatitis B; Children; Hepatitis B Virus Infection
• Intervention / Treatment: Drug: Entecavir; Drug: Entecavir + Pegylated interferon α-2b

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Qing-Lei Zeng, M.D.; Phone Number: 86 15838120512; Email: zengqinglei2009@163.com
• Study Contact Backup: Name: Zu-Jiang Yu, M.D.; Phone Number: 86 186 0371 0022; Email: johnyuem@zzu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Entecavir; Receive entecavir monotherapy throughout the 96-week treatment course.	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.; Other Names: Runzhong®
Experimental: Entecavir plus Peg-IFN α-2b; Receive entecavir for the first 48 weeks, followed by combination therapy with pegylated interferon α-2b for the remaining 48 weeks.	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.; Other Names: Runzhong®; PEGBING®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 24 weeks after treatment cessation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of HBV DNA undetectable	Proportion of participants with HBV DNA undetectable, defined as HBV DNA <10 IU/mL.	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.	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.	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.	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.	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	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.	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 .	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.	At any time during study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.

Collaborators and Investigators

• Sponsor: Qing-Lei Zeng
• Collaborators: Henan Provincial People's Hospital; Luoyang Central Hospital; Nanyang Central Hospital; Sanmenxia Central Hospital; The Sixth People's Hospital of Zhengzhou; Luohe Central Hospital; Xuchang Central Hospital; Yongcheng People's Hospital; The Third Affiliated Hospital of Henan Medical University; Weishi County People's Hospital; The First Affiliated Hospital of Henan Medical University; Shangcheng County People's Hospital; The First Affiliated Hospital of Henan Polytechnic University
• Investigators: Principal Investigator: Qing-Lei Zeng, M.D., The first affiliated hospital of Zhengzhou university

Study record dates

Study Major Dates

• Study Start (Estimated): January 11, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 24, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Children; Chronic; Entecavir; Hepatitis B virus; Functional cure; Pegylated interferon α-2b; Immune-tolerant
• Additional Relevant MeSH Terms: Blood-Borne Infections; Organizing Pneumonia; Pathologic Processes; Chronic Disease; Disease Attributes; Immune System Diseases; Infections; Virus Diseases; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Hepatitis; Graft vs Host Disease; Pathological Conditions, Signs and Symptoms; Bronchiolitis Obliterans Syndrome; Hepatitis B; Hepatitis B, Chronic; entecavir
• Other Study ID Numbers: 2025-KY-1632-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No