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A Study on Antiviral Treatment of Chronic Hepatitis B in Children

Primary Purpose

Chronic HBV Infection

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Peginterferon alfa-2b combined and ETV
Sponsored by
Fang Wang
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic HBV Infection

Eligibility Criteria

3 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 1.Inclusion criteria for treatment-naïve children with hepatitis B: Aged 3 to 18 (included 3 years old, but exclude 18 years old); HBV DNA positive (higher than the lower detection limit or >20 IU/ml. Roche reagent is recommended). HBsAg positive (higher than lower detection limit or >0.05 IU/ml. Roche reagent is recommended). ALT flares between 1 to10 ULN at least twice a year. If the last examination result is higher than 5ULN, the investigator shall comprehensively judge whether the child patient is suitable to participate in this study. The guardian should understand and sign the informed consent form (if parents is the legal guardians, they both must sign the informed consent form). Children older than 8 years (included) also must sign the informed consent form. The consent comment of child patient under the age of 8 should also be clearly recorded. 2.Inclusion criteria for NA-treated children with hepatitis B: Aged 3 to 18 (included 3 years old, but exclude 18 years old); Previously received NA treatment for ≥ 1 year. HBsAg positive (higher than lower detection limit or >0.05 IU/ml. Roche reagent is recommended). The guardian should understand and sign the informed consent form (if parents is the legal guardians, they both must sign the informed consent form). Children older than 8 years (included) also must sign the informed consent form. The consent comment of child patient under the age of 8 should also be clearly recorded. 3.Inclusion criteria for chronic HBV carrying children with normal ALT: Aged 3 to 18 (included 3 years old, but exclude 18 years old); HBV DNA positive (higher than lower detection limit or >20 IU/ml. Roche reagent is recommended). HBsAg positive (higher than lower detection limit or >0.05 IU/ml. Roche reagent is recommended). Serum ALT and AST remain persistently normal (2 consecutive follow-up visits within half a year, with an interval of at least 3 months) TThe guardian should understand and sign the informed consent form (if parents is the legal guardians, they both must sign the informed consent form). Children older than 8 years (included) also must sign the informed consent form. The consent comment of child patient under the age of 8 should also be clearly recorded. Exclusion Criteria: Co-infected with HAV, HCV, HDV, HEV or HIV. Patients with contraindications to peginterferon alfa-2b, including but not limit to : Hepatitis B cirrhosis decompensated stage. Child patient with autoimmune liver disease, metabolic liver disease or alcoholic liver disease; malignant tumor, decompensated liver disease, or organ transplantation. Child patient with severe neurological or mental disorders. Child patient with severe hyperthyroidism or other autoimmune disorders. Child patient with diabetes under poorly controlled. Child patient with retinal or fundus lesions. Child patient with severe heart disease, coronary heart disease or cerebrovascular disease. Child patient with poorly controlled epilepsy. Child patient with severe renal dysfunction, e.g. creatinine > 1.5 ULN. Child patient who in the opinion of the investigator is unsuitable for enrollment.

Sites / Locations

  • Shenzhen Third People HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

treatment-naïve children with hepatitis B

previously treated children with hepatitis B

chronic HBV carrying children with normal ALT

Arm Description

Outcomes

Primary Outcome Measures

Clinical cure rate.
Defined as the proportion of child patients with HBsAg < 0.05 IU / mL (or below the lower detection limit) 24 weeks after completing treatment, HBeAg negative, HBV DNA undetectable, and normalization of liver biochemical indexes (ALT and AST).

Secondary Outcome Measures

Proportion of patients with HBV-DNA negative in those with HBV-DNA positive at baseline.
Defined as HBV-DNA below the lower detection limit, or< 20 IU/mL.
HBeAg seroconversion rate in HBeAg positive children.
Defined as HBeAg negative and anti-HBe positive.
HBsAg seroconversion rate.
Defined as HBsAg < 0.05 IU/mL and anti-HBe positive.
ALT normalization rate.
Decrease of HBV-DNA compared to baseline.
Decrease of HBeAg compared to baseline.
Decrease of HBsAg compared to baseline.
The incidence of adverse reactions.
Including fever, influenza-like symptoms, decreased hemogram, jaundice ALT> 400U/L, abnormal renal function, abnormal thyroid function, abnormal blood phosphorus and blood calcium during treatment (lower or higher than the normal value).
The effects on height
The effects on weight
The effects on bone age.

Full Information

First Posted
February 23, 2023
Last Updated
March 19, 2023
Sponsor
Fang Wang
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1. Study Identification

Unique Protocol Identification Number
NCT05792761
Brief Title
A Study on Antiviral Treatment of Chronic Hepatitis B in Children
Official Title
A Study on Antiviral Treatment of Chronic Hepatitis B in Children (Sprout Project)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 6, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Fang Wang

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
There are nearly 2 million HBsAg-positive children who are in urgent need of professional diagnosis and treatment in China. Chronic hepatitis B (CHB) is the leading cause of childhood liver disease. After infected with HBV virus, some children will develop disease progression, and some even develop cirrhosis and/or liver cancer. In pediatric liver cancer cases, up to 34% ~ 95% are caused by HBV infection. Although two major classes of drugs have been approved for the treatment of chronic hepatitis B in adults, and there are multiple guidelines worldwide for the management of HBV infection in adults, there is lack of guidelines specifically for the management of children with HBV infection. In addition, the treatment of chronic hepatitis B in children faced great difficulties due to the lack of evidence-based medical evidence for antiviral treatment of chronic hepatitis B in children and fewer drugs approved for anti-HBV treatment in children. The timing of treatment, medications, and clinical management strategies are all controversial. This study ( Sprout project),is a multicenter, prospective, cohort study in China, aiming to explore and optimize the antiviral treatment regimen for children with HBV infection, to provide evidence-based medical for antiviral treatment, and to provide basis evidence for the standardized management of children infection with HBV in China. The study is expected to enroll 1900 pediatric patients with HBV infection, and patient will received one of the three following treatment Strategies: nucleoside monotherapy, peginterferon α- combined with nucleoside therapy, or peginterferon α-pulse therapy combined with nucleoside therapy, according to their illness state and desire, and the safety and efficacy will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic HBV Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1900 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
treatment-naïve children with hepatitis B
Arm Type
Experimental
Arm Title
previously treated children with hepatitis B
Arm Type
Experimental
Arm Title
chronic HBV carrying children with normal ALT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Peginterferon alfa-2b combined and ETV
Intervention Description
Child patients are assigned to one of the 3 treatment regimens according to their illness state and treatment desire of their parents/guardians, and the number of patients in each group is expected to limited to 300. NA monotherapy group : received entecavir (ETV) for 96 weeks. Combination therapy group: received peginterferon alfa-2b combined with ETV for 96 weeks. Pulse therapy group :received peginterferon alfa-2b pulse treatment combined with ETV for 144 weeks.
Primary Outcome Measure Information:
Title
Clinical cure rate.
Description
Defined as the proportion of child patients with HBsAg < 0.05 IU / mL (or below the lower detection limit) 24 weeks after completing treatment, HBeAg negative, HBV DNA undetectable, and normalization of liver biochemical indexes (ALT and AST).
Time Frame
24 weeks after completing treatment.
Secondary Outcome Measure Information:
Title
Proportion of patients with HBV-DNA negative in those with HBV-DNA positive at baseline.
Description
Defined as HBV-DNA below the lower detection limit, or< 20 IU/mL.
Time Frame
24 weeks after treatment completion
Title
HBeAg seroconversion rate in HBeAg positive children.
Description
Defined as HBeAg negative and anti-HBe positive.
Time Frame
24 weeks after treatment completion.
Title
HBsAg seroconversion rate.
Description
Defined as HBsAg < 0.05 IU/mL and anti-HBe positive.
Time Frame
24 weeks after treatment completion.
Title
ALT normalization rate.
Time Frame
48 weeks and 96 weeks after starting treatment
Title
Decrease of HBV-DNA compared to baseline.
Time Frame
24 weeks after treatment completion.
Title
Decrease of HBeAg compared to baseline.
Time Frame
24 weeks after treatment completion.
Title
Decrease of HBsAg compared to baseline.
Time Frame
24 weeks after treatment completion.
Title
The incidence of adverse reactions.
Description
Including fever, influenza-like symptoms, decreased hemogram, jaundice ALT> 400U/L, abnormal renal function, abnormal thyroid function, abnormal blood phosphorus and blood calcium during treatment (lower or higher than the normal value).
Time Frame
24weeks ,48 weeks and 96 weeks after starting treatment
Title
The effects on height
Time Frame
24weeks ,48 weeks and 96 weeks after starting treatment
Title
The effects on weight
Time Frame
24weeks ,48 weeks and 96 weeks after starting treatment
Title
The effects on bone age.
Time Frame
24weeks ,48 weeks and 96 weeks after starting treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1.Inclusion criteria for treatment-naïve children with hepatitis B: Aged 3 to 18 (included 3 years old, but exclude 18 years old); HBV DNA positive (higher than the lower detection limit or >20 IU/ml. Roche reagent is recommended). HBsAg positive (higher than lower detection limit or >0.05 IU/ml. Roche reagent is recommended). ALT flares between 1 to10 ULN at least twice a year. If the last examination result is higher than 5ULN, the investigator shall comprehensively judge whether the child patient is suitable to participate in this study. The guardian should understand and sign the informed consent form (if parents is the legal guardians, they both must sign the informed consent form). Children older than 8 years (included) also must sign the informed consent form. The consent comment of child patient under the age of 8 should also be clearly recorded. 2.Inclusion criteria for NA-treated children with hepatitis B: Aged 3 to 18 (included 3 years old, but exclude 18 years old); Previously received NA treatment for ≥ 1 year. HBsAg positive (higher than lower detection limit or >0.05 IU/ml. Roche reagent is recommended). The guardian should understand and sign the informed consent form (if parents is the legal guardians, they both must sign the informed consent form). Children older than 8 years (included) also must sign the informed consent form. The consent comment of child patient under the age of 8 should also be clearly recorded. 3.Inclusion criteria for chronic HBV carrying children with normal ALT: Aged 3 to 18 (included 3 years old, but exclude 18 years old); HBV DNA positive (higher than lower detection limit or >20 IU/ml. Roche reagent is recommended). HBsAg positive (higher than lower detection limit or >0.05 IU/ml. Roche reagent is recommended). Serum ALT and AST remain persistently normal (2 consecutive follow-up visits within half a year, with an interval of at least 3 months) TThe guardian should understand and sign the informed consent form (if parents is the legal guardians, they both must sign the informed consent form). Children older than 8 years (included) also must sign the informed consent form. The consent comment of child patient under the age of 8 should also be clearly recorded. Exclusion Criteria: Co-infected with HAV, HCV, HDV, HEV or HIV. Patients with contraindications to peginterferon alfa-2b, including but not limit to : Hepatitis B cirrhosis decompensated stage. Child patient with autoimmune liver disease, metabolic liver disease or alcoholic liver disease; malignant tumor, decompensated liver disease, or organ transplantation. Child patient with severe neurological or mental disorders. Child patient with severe hyperthyroidism or other autoimmune disorders. Child patient with diabetes under poorly controlled. Child patient with retinal or fundus lesions. Child patient with severe heart disease, coronary heart disease or cerebrovascular disease. Child patient with poorly controlled epilepsy. Child patient with severe renal dysfunction, e.g. creatinine > 1.5 ULN. Child patient who in the opinion of the investigator is unsuitable for enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fang Wang
Phone
+8613682662543
Email
kaixin919@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Qing He
Organizational Affiliation
Shenzhen Third People's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hongfei Zhang
Organizational Affiliation
Beijing Tsinghua Changgeng Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Fang Wang
Organizational Affiliation
Shenzhen Third People's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Shenzhen Third People Hospital
City
Shenzhen
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fang Wang
Phone
+8613682662543
Email
kaixin919@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study on Antiviral Treatment of Chronic Hepatitis B in Children

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