Study on Antiviral Therapy for HBeAg-positive Chronic Hepatitis B Patients Aged 1-16 Years

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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HBeAg Positive Chronic Hepatitis B

Intervention / Treatment
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* Drug: NAs+IFN-α


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 1 to 16 years old. Chronic Hepatitis B (CHB) patients or HBsAg positive > 6 months patients who are line with the diagnostic criteria for chronic hepatitis B infection. ALT:40～400 U/L. HBeAg positive. HBV DNA>2×104IU/L. Liver histology: G<3. 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: 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. Combined with HAV、HCV、HDV、HEV or HIV-infected persons. 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. Patients with decompensated cirrhosis，including ascites. Received the following medications（Immunosuppressant and Systemic cytotoxic drugs）in six months. Patients who are allergy to IFNs and NAs; 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. Patients who unable to comply with the study arrangement judged by researcher.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAs+IFN-α<br>NAs+IFN-α/ 96w | Drug: NAs+IFN-α<br>* NAs+IFN-α:(NAs +IFN)/96 weeks：NAs（when the CHB patients<2years old, the drug is LAM）combined with IFN-α（when the CHB patients<3years old, the drug is IFN-α）for 96 weeks。 NAs+(NAs+IFN-α) :NAs/48weeks+(NAs+ IFN)/96 weeks：NAs（when the CHB patients<2years old, the drug is LAM）for 48 weeks ，then combined with IFN-α（when the CHB patients<3years old, the drug is IFN-α）for 96weeks。 Response guided treatment（RGT） by HBsAg quantification： The course of interferon alpha was 24 weeks after HBsAg and HBeAg turned negative up to 96 weeks, and NAs was discontinued 12 months after HBsAg serological conversion.<br>|
| Other: NAs+(IFN-α+ NAs )<br>NAs/48w+(IFN-α+ NAs)/96w | Drug: NAs+IFN-α<br>* NAs+IFN-α:(NAs +IFN)/96 weeks：NAs（when the CHB patients<2years old, the drug is LAM）combined with IFN-α（when the CHB patients<3years old, the drug is IFN-α）for 96 weeks。 NAs+(NAs+IFN-α) :NAs/48weeks+(NAs+ IFN)/96 weeks：NAs（when the CHB patients<2years old, the drug is LAM）for 48 weeks ，then combined with IFN-α（when the CHB patients<3years old, the drug is IFN-α）for 96weeks。 Response guided treatment（RGT） by HBsAg quantification： The course of interferon alpha was 24 weeks after HBsAg and HBeAg turned negative up to 96 weeks, and NAs was discontinued 12 months after HBsAg serological conversion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rates of HBsAg serological disappearance / conversion in CHB patients at 48 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 48 weeks | 48 weeks | 
| The rates of HBsAg serological disappearance / conversion in CHB patients at 96 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 96 weeks | 96 weeks | 
| The rates of HBsAg serological disappearance / conversion in CHB patients at 144 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 144 weeks | 144 weeks | 
| The rates of HBsAg serological disappearance / conversion in CHB patients at 168 weeks | The rates of HBsAg serological disappearance / conversion in CHB patients at 168 weeks | 168 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of HBeAg clearance / seroconversion | The rate of HBeAg clearance / seroconversion in patients with CHB | 168 weeks | 
| HBV DNA negative conversion rate | HBV DNA negative conversion rate in patients with CHB | 168 weeks | 
| ALT(Alanine aminotransferase) recovery rate | ALT recovery rate in patients with CHB | 168 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis B,chronic; Interferon ; Nucleosides;child