Clinical trial NCT05792761: 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
Overall status: RECRUITING
Phase: NA
Conditions: Chronic HBV Infection
Lead sponsor: Shenzhen Third People's Hospital
Sponsor class: OTHER
First posted: 2023-03-31
Enrollment: 1900
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1.Inclusion criteria for treatment-naïve children with hepatitis B:

1. Aged 3 to 18 (included 3 years old, but exclude 18 years old);
2. HBV DNA positive (higher than the lower detection limit or \>20 IU/ml. Roche reagent is recommended).
3. HBsAg positive (higher than lower detection limit or \>0.05 IU/ml. Roche reagent is recommended).
4. 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.
5. 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:

1. Aged 3 to 18 (included 3 years old, but exclude 18 years old);
2. Previously received NA treatment for ≥ 1 year.
3. HBsAg positive (higher than lower detection limit or \>0.05 IU/ml. Roche reagent is recommended).
4. 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:

1. Aged 3 to 18 (included 3 years old, but exclude 18 years old);
2. HBV DNA positive (higher than lower detection limit or \>20 IU/ml. Roche reagent is recommended).
3. HBsAg positive (higher than lower detection limit or \>0.05 IU/ml. Roche reagent is recommended).
4. Serum ALT and AST remain persistently normal (2 consecutive follow-up visits within half a year, with an interval of at least 3 months)
5. 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:

1. Co-infected with HAV, HCV, HDV, HEV or HIV.
2. Patients with contraindications to peginterferon alfa-2b, including but not limit to :

   1. Hepatitis B cirrhosis decompensated stage.
   2. Child patient with autoimmune liver disease, metabolic liver disease or alcoholic liver disease; malignant tumor, decompensated liver disease, or organ transplantation.
   3. Child patient with severe neurological or mental disorders.
   4. Child patient with severe hyperthyroidism or other autoimmune disorders.
   5. Child patient with diabetes under poorly controlled.
   6. Child patient with retinal or fundus lesions.
   7. Child patient with severe heart disease, coronary heart disease or cerebrovascular disease.
   8. Child patient with poorly controlled epilepsy.
3. Child patient with severe renal dysfunction, e.g. creatinine \> 1.5 ULN.
4. Child patient who in the opinion of the investigator is unsuitable for enrollment.

Primary outcomes:
measure: Clinical cure rate.
timeFrame: 24 weeks after completing treatment.
Secondary outcomes:
measure: Proportion of patients with HBV-DNA negative in those with HBV-DNA positive at baseline.
timeFrame: 24 weeks after treatment completion
measure: HBeAg seroconversion rate in HBeAg positive children.
timeFrame: 24 weeks after treatment completion.
measure: HBsAg seroconversion rate.
timeFrame: 24 weeks after treatment completion.
measure: ALT normalization rate.
timeFrame: 48 weeks and 96 weeks after starting treatment
measure: Decrease of HBV-DNA compared to baseline.
timeFrame: 24 weeks after treatment completion.
measure: Decrease of HBeAg compared to baseline.
timeFrame: 24 weeks after treatment completion.
measure: Decrease of HBsAg compared to baseline.
timeFrame: 24 weeks after treatment completion.
measure: The incidence of adverse reactions.
timeFrame: 24weeks ,48 weeks and 96 weeks after starting treatment
measure: The effects on height
timeFrame: 24weeks ,48 weeks and 96 weeks after starting treatment
measure: The effects on weight
timeFrame: 24weeks ,48 weeks and 96 weeks after starting treatment
measure: The effects on bone age.
timeFrame: 24weeks ,48 weeks and 96 weeks after starting treatment
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Third People Hospital
Study officials:
affiliation: Shenzhen Third People's Hospital
name: Qing He
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Tsinghua Changgeng Hospital
name: Hongfei Zhang
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen Third People's Hospital
name: Fang Wang
role: STUDY_CHAIR
References: