Clinical Trial of Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic HBV Infection (HBRN)
Overview
- Phase
- Phase 3
- Intervention
- Entecavir and peginterferon
- Conditions
- Hepatitis B
- Sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Enrollment
- 60
- Locations
- 7
- Primary Endpoint
- Incidence of Serious Adverse Events (SAEs) Per Person-Year
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to determine the safety and efficacy of treatment using a combination of drugs (entecavir and pegylated interferon) in children ages 3-<18 years old with immunotolerant chronic hepatitis B.
Detailed Description
This single arm treatment study was conducted by the pediatric centers within the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK)-sponsored Hepatitis B Research Network (HBRN). Children age 3-\<18 years with immunotolerant chronic hepatitis B (CHB) infection who fulfilled the entry criteria received entecavir as monotherapy for 8 weeks and then combination therapy with entecavir and pegylated interferon by weekly subcutaneous injection until week 48. Children were to be followed for 48 weeks after discontinuation of therapy (week 96 for those who completed 48 weeks of treatment). Assessment was undertaken at baseline, weeks 4, 8, 10, 12, 14, \& 16, then every 4 weeks until week 48, and then 4, 8, 12, 24,36, and 48 weeks following treatment discontinuation corresponding to weeks 52, 56, 60, 72, 84 and 96 for those who received treatment for 48 weeks. Blood work was drawn to measure markers of viral and liver disease status and for research biospecimen banking. Participants were to receive therapy until week 48 and enter 48 weeks of follow-up thereafter. Participants who experienced a sustained elevation of alanine aminotransferase (ALT) were eligible to receive treatment as recommended by their hepatologist and continued to complete the study protocol.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Enrolled in \& completed the baseline evaluation in NCT01263600 OR completed necessary components of NCT01263600 baseline evaluation by the end of the baseline visit.
- •3 to \<18 years at time of randomization (day 0).
- •Documented chronic Hepatitis B virus (HBV) infection as evidenced by detection of hepatitis B surface antigen (HBsAg) in serum for ≥ 24 weeks prior to baseline OR positive HBsAg and negative anti-Hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks of baseline visit.
- •Presence of hepatitis B e-antigen (HBeAg) in serum at the last screening visit within 6 weeks of baseline visit.
- •Serum HBV DNA level \>10\^7 IU/mL on at least 2 occasions at least 12 weeks apart during the 52 weeks before baseline visit. The HBV DNA levels must be within 6 weeks of baseline visit.
- •ALT ≤60 U/l in males or ≤40 U/l in females, measured on at least 2 occasions, at screening (within 6 weeks prior to baseline visit) \& at least 12 weeks prior to the screening visit \& within the 52 weeks prior to baseline visit.
- •Compensated liver disease, with normal total bilirubin (except if Gilbert's syndrome), direct bilirubin ≤0.5 mg/dL, International Normalized Ratio (INR) ≤1.5, and serum albumin ≥3.5 g/dL.
- •Creatinine clearance 90 ml/min.
- •Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks.
- •Exclusion criteria:
Exclusion Criteria
- Not provided
Arms & Interventions
Entecavir and peginterferon
Entecavir for 8 weeks followed by 40 weeks of both entecavir and peginterferon
Intervention: Entecavir and peginterferon
Outcomes
Primary Outcomes
Incidence of Serious Adverse Events (SAEs) Per Person-Year
Time Frame: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
The incidence is calculated as the number of SAEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
Incidence of Adverse Events (AEs) Per Person-Year
Time Frame: From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)
The number of AEs includes both AEs and Serious Adverse Events (SAEs). The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.
Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss & Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Levels ≤1,000 International Units (IU) Per Milliliter (mL)
Time Frame: End of follow-up (up to 96 weeks)
Secondary Outcomes
- Proportion of Participants With HBeAg Seroconversion(End of follow-up (up to 96 weeks))
- Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss(End of follow-up (up to 96 weeks))
- Proportion of Participants With ALT ≤ 40 U/L for Males, ≤ 35 U/L for Females(End of follow-up (up to 96 weeks))
- Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss(End of follow-up (up to 96 weeks))
- Proportion of Participants With HBV DNA < 20 IU/mL(End of follow-up (up to 96 weeks))
- Growth Measures: Z-scores Weight, Height, and Body Mass Index(End of follow-up (up to 96 weeks))
- Proportion of Participants With HBV DNA ≤1000 IU/mL(End of follow-up (up to 96 weeks))
- Proportion of Participants With HBsAg Seroconversion(End of follow-up (up to 96 weeks))
- Proportion of Participants With Alanine Aminotransferase (ALT) ≤ 40 Units (U) Per Liter (L) for Males, ≤ 35 U/L for Females(End of treatment (up to 48 weeks))
- Tanner Stages of Pubic Hair Growth(End of follow-up (up to 96 weeks))
- Proportion Without Detectable Antiviral Drug-resistance HBV Mutations(End of treatment (up to 48 weeks))
- Tanner Stages of Physical Growth(End of follow-up (up to 96 weeks))