Clinical trial NCT04565262: Study on Antiviral Therapy for HBeAg-positive Chronic Hepatitis B Patients Aged 1-16 Years
Official title: Multi-center Study of IFN Combined With Nucleosides Analog Antiviral Therapy in Pediatric Patients With HBeAg Positive Chronic Hepatitis B (CHB) Aged 1-16 Years
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HBeAg Positive Chronic Hepatitis B
Keywords: hepatitis B,chronic; Interferon ; Nucleosides;child
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2020-09-25
Enrollment: 200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: These subjects will be randomized (1:1) to group A(treated with NAs + IFN for 96 weeks) and group B(treated with NAs for 48 weeks, then NAs combined with IFN for 96 weeks).Meanwhile, 1-6 years and 7-16 years patients should be distributed by 1:1 ratio by random method in both groups.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to provide theoretical and real world evidence for the optimization of antiviral treatment by IFN combined with Nucleosides analog in HBeAg positive chronic hepatitis B patients aged 1-16 years，so that the functional cure could be achieved in the greatest extent in pediatric patients

Detailed description: This research is a national multicenter, randomized, prospective study. The planned sample size is 200 subjects in 1-16 years pediatric patients with HBeAg positive Chronic Hepatitis B (CHB). These subjects will be randomized (1:1) to group A(treated with NAs + IFN for 96 weeks) and group B(treated with NAs for 48 weeks, then NAs combined with IFN for 96 weeks).Meanwhile, 1-6 years and 7-16 years patients should be distributed by 1:1 ratio by random method in both groups. Regularly Blood cell count, biochemical test, hepatitis B viral markers test, and lymphocyte subsets test were exerted. To compare the curative effect of group A and group B, The primary monitoring indicator is HBsAg clearance rate, and the secondary monitoring indicator is hepatitis B virus (HBV) DNA clearance，HBeAg seroconversion in these patients,. So that we can make the optimal antiviral treatment strategy for 1-16-year-old children with CHB，and try to find out the possible influencing factors of function cure

Eligibility criteria: Inclusion Criteria:

1. Aged 1 to 16 years old.
2. Chronic Hepatitis B (CHB) patients or HBsAg positive \> 6 months patients who are line with the diagnostic criteria for chronic hepatitis B infection.
3. ALT:40～400 U/L.
4. HBeAg positive.
5. HBV DNA\>2×104IU/L.
6. Liver histology: G\<3.
7. Agree to sign the Informed Consent Form (Children aged 1-6 years may be signed by the guardian; children between the ages of 7 and 11 are in principle signed by the child and the guardian; those over the age of 12 must be signed by the child and the guardian)

Exclusion Criteria:

1. white blood cell (WBC)\< 3.5×109/L，PLT\< 80×1012/L，Pt A\<60%，total bilirubin (TBIL)\>34umol/L，ALB\<35g/L，Cr\>133umol/L.
2. Combined with HAV、HCV、HDV、HEV or HIV-infected persons.
3. Patients combined with other causes of liver disease：alcoholic or non-alcoholic liver disease，thyroid disease，autoimmune liver disease，genetic metabolic liver disease，bile duct diseases，or Parasitic infection of hepatobiliary tract.
4. Patients with decompensated cirrhosis，including ascites.
5. Received the following medications（Immunosuppressant and Systemic cytotoxic drugs）in six months.
6. Patients who are allergy to IFNs and NAs;
7. Patients with other severe or active psychosomatic diseases （kidney, heart, lungs, vascular, neurological, digestive including history of pancreatitis, metabolic diseases including diabetes, thyroid and Adrenal disease, adrenal disease or tumor), Researchers believe which affect the treatment, evaluation or compliance of patients with the study plan.
8. Patients who unable to comply with the study arrangement judged by researcher.

Primary outcomes:
measure: The rates of HBsAg serological disappearance / conversion in CHB patients at 48 weeks
timeFrame: 48 weeks
measure: The rates of HBsAg serological disappearance / conversion in CHB patients at 96 weeks
timeFrame: 96 weeks
measure: The rates of HBsAg serological disappearance / conversion in CHB patients at 144 weeks
timeFrame: 144 weeks
measure: The rates of HBsAg serological disappearance / conversion in CHB patients at 168 weeks
timeFrame: 168 weeks
Secondary outcomes:
measure: The rate of HBeAg clearance / seroconversion
timeFrame: 168 weeks
measure: HBV DNA negative conversion rate
timeFrame: 168 weeks
measure: ALT(Alanine aminotransferase) recovery rate
timeFrame: 168 weeks
Other outcomes:
measure: Number of participants with treatment-related side effect and safety events as assessed by GSI
timeFrame: 168 weeks
measure: Average duration of HBeAg seroconversion
timeFrame: 168 weeks
measure: Average duration of disappearance of HBsAg
timeFrame: 168 weeks
measure: Assessed the changes of liver stiffness measure by FibroScan after antiviral therapy
timeFrame: 168 weeks
measure: Rate of relapse in patients after stop of antiviral therapy of NAs
timeFrame: 168 weeks
Locations:
city: Beijing
country: China
facility: Min Zhang
state: Beijing
Study officials:
affiliation: Beijing 302 Hospital
name: Min Zhang, Dcotor
role: PRINCIPAL_INVESTIGATOR
References: