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

HBeAg Positive Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04565262
• Other study ID #: R2020050DA010
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 2020
• Est. completion date: September 2023

Study information

• Verified date: August 2020
• Source: Beijing 302 Hospital
• Contact: Min Zhang, Doctor
• Phone: 13911517721
• Email: gcmw2001[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: September 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• HBeAg Positive Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• NAs+IFN-a
NAs+IFN-a:(NAs +IFN)/96 weeks:NAs(when the CHB patients<2years old, the drug is LAM)combined with IFN-a(when the CHB patients<3years old, the drug is IFN-a)for 96 weeks? NAs+(NAs+IFN-a) :NAs/48weeks+(NAs+ IFN)/96 weeks:NAs(when the CHB patients<2years old, the drug is LAM)for 48 weeks ,then combined with IFN-a(when the CHB patients<3years old, the drug is IFN-a)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.

Locations

Country	Name	City	State
China	Min Zhang	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing 302 Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants with treatment-related side effect and safety events as assessed by GSI	Side effect and safety events include adverse events, adverse drug reactions etc. during the treatment	168 weeks
Other	Average duration of HBeAg seroconversion	Average duration of HBeAg seroconversion during treatment	168 weeks
Other	Average duration of disappearance of HBsAg	Average duration of disappearance of HBsAg during treatment	168 weeks
Other	Assessed the changes of liver stiffness measure by FibroScan after antiviral therapy	Comparison the changes of liver stiffness before and after antiviral treatment (evaluated by FibroScan)	168 weeks
Other	Rate of relapse in patients after stop of antiviral therapy of NAs	Rate of relapse in patients after stop of antiviral therapy of NAs	168 weeks
Primary	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
Primary	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
Primary	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
Primary	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	The rate of HBeAg clearance / seroconversion	The rate of HBeAg clearance / seroconversion in patients with CHB	168 weeks
Secondary	HBV DNA negative conversion rate	HBV DNA negative conversion rate in patients with CHB	168 weeks
Secondary	ALT(Alanine aminotransferase) recovery rate	ALT recovery rate in patients with CHB	168 weeks