Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen–positive chronic hepatitis B

Abstract

This ongoing, randomized phase III study assesses the safety and efficacy of entecavir versus placebo in nucleos(t)ide-na€ ıve children (2 to <18 years) with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B (CHB). Blinded treatment was administered for a minimum of 48 weeks. After week 48, patients with HBeAg seroconversion continued blinded treatment; those without switched to open-label entecavir. The primary endpoint was HBeAg seroconversion and HBV DNA <50 IU/mL at week 48. A total of 180 patients were randomized (2:1) and treated. Baseline median age was 12 years, with approximately 50% of children ages >12 to <18, and 25% each ages !2 to £ 6 and >6 to £ 12. Rates for the primary endpoint at week 48 were significantly higher with entecavir than placebo (24.2% [29 of 120] 60]; P 5 0.0210). Among entecavir-randomized patients, there was an increase in all efficacy endpoints between weeks 48 and 96, including an increase from 49% to 64% in virological suppression. The cumulative probability of emergent entecavir resistance through years 1 and 2 of entecavir was 0.6% and 2.6%, respectively. Entecavir was well tolerated with no observed differences in adverse events or changes in growth compared with placebo. Conclusion: In childhood CHB, entecavir demonstrated superior antiviral efficacy to placebo with a favorable safety profile. These results support the use of entecavir as a therapeutic option in children and adolescents with CHB.

AASLD guidelines for treatment of chronic hepatitis B

“…The evidence profile is summarized in http://onlinelibrary.wiley.com/doi/10.1002/hep.28156/suppinfo . Additionally, in a recent multinational RCT in children ages 2‐18, a significantly higher rate of HBeAg seroconversion plus HBV DNA <50 IU/mL was achieved with entecavir compared to placebo (24.4% vs. 2.4%; P = 0.005) . Not all of the reviewed studies had the same primary endpoints.…”

Using Population Pharmacokinetic and Pharmacodynamic Analyses of Entecavir in Pediatric Subjects to Simplify Dosing Recommendations

“…Pediatric subjects were administered entecavir orally, as tablets or solutions, at doses from 0.015 mg/kg/day up to 0.5 mg/day for those who were lamivudine naïve or 0.030 mg/kg/day up to 1 mg/day for those who were lamivudine experienced [7]. Adult subjects included in the analysis had been treated with capsules at 0.01-1 mg/day.…”

“…Following the completion of successful phase II/III pediatric clinical trials in 2014, entecavir was approved in the USA and EU for the treatment of CHB in children at least 2 years of age [7]. Entecavir is primarily eliminated by renal clearance through both passive (filtration) and active transport processes, and is not a substrate for the cytochrome P450 enzyme system [5].…”

Long‐term efficacy and safety of peginterferon in the treatment of children with HBeAg‐positive chronic hepatitis B

“…Although ETV has been approved for CHB in patients over 2 years old, it has lower virological suppression rate and higher resistance rate in children than it does in adults . Following 48 weeks of treatment, HBeAg conversion rate was 24.2%, and the HBsAg clearance rate was 1.7% . TDF was approved only for treating children over 12 years old, which could reduce bone density .…”