Children, Chronic Hepatitis B, Hepatitis B Virus Infection
Conditions
Keywords
Children, Efficacy, Safety, Chronic, Pegylated interferon α-2b, Hepatitis B virus, Entecavir, Functional cure, Immune-tolerant
Brief summary
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
DRUGEntecavir
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.
Sponsors
Henan Provincial People's Hospital
Luoyang Central Hospital
Xuchang Central Hospital
Luohe Central Hospital
Yongcheng People's Hospital
Sanmenxia Central Hospital
The Third Affiliated Hospital of Henan Medical University
Weishi County People's Hospital
The Sixth People's Hospital of Zhengzhou
The First Affiliated Hospital of Henan Medical University
Shangcheng County People's Hospital
The First Affiliated Hospital of Henan Polytechnic University
Nanyang Central Hospital
Qing-Lei Zeng
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
3 Years to 6 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The rate of functional cure | At 24 weeks after treatment cessation. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The rate of HBeAg loss | At week 24, 48, 72, 96, 120 of the study. | Proportion of participants with HBeAg loss, defined as HBeAg \<0.18 PEIU/mL. |
| The rate of HBsAg loss | At week 24, 48, 72, 96, 120 of the study. | Proportion of participants with HBsAg loss, defined as HBsAg \<0.05 IU/mL. |
| The rate of alanine aminotransferase elevation or flare | At any time during the study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation. | 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. |
| The rate of HBV DNA undetectable | At week 24, 48, 72, 96, 120 of the study. | Proportion of participants with HBV DNA undetectable, defined as HBV DNA \<10 IU/mL. |
| The rate of growth suppression | At week 24, 48, 60, 72, 84, 96, 108, 120 of the study. | 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. |
| The rate of thyroid dysfunction | At week 72, 96, and 120 of the study. | 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 . |
| Any other adverse event | At any time during study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation. | 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. |
| The rate of cytopenia rate | At any time during the study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation. | Proportion of participants with cytopenia, defined as an absolute neutrophil count \<1.0×10⁹/L and/or a platelet count \<100×10⁹/L. |
Contacts
Primary ContactQing-Lei Zeng, M.D.
Backup ContactZu-Jiang Yu, M.D.
Outcome results
None listed