1Boston Children's Hospital, Boston, MA.
2National Taiwan University Hospital, Taipei, Taiwan.
3Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.
4Johns Hopkins Children's Center, Baltimore, MD.
5Birmingham Children's Hospital, Birmingham, UK.
6Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
7The Hospital For Sick Children, and Department of Paediatrics, University of Toronto, Toronto, Canada.
8University of California, San Francisco, CA.
9Grigore Alexandrescu Emergency Hospital for Children, Bucharest, Romania.
10Bristol-Myers Squibb, Wallingford, CT.
This ongoing, randomized phase III study assesses the safety and efficacy of entecavir versus placebo in nucleos(t)ide-naive children (2 to <18 years) with 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 aged >12 to <18, and 25% each aged ≥2 to ≤6 and >6 to ≤12. Rates for the primary endpoint at Week 48 were significantly higher with entecavir than placebo (24.2% [29/120] versus 3.3% [2/60]; P=0.0008). Furthermore, higher response rates were observed with entecavir compared with placebo for the key Week 48 secondary endpoints: HBV DNA <50 IU/mL (49.2% [59/120] versus 3.3% [2/60]; P < 0.0001), alanine aminotransferase normalization (67.5% [81/120] versus 23.3% [14/60]; P < 0.0001), and HBeAg seroconversion (24.2% [29/120] versus 10.0% [6/60]; P = 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 virologic 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.
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.