Randomized Controlled Trial of Entecavir Versus Placebo in Children with HBeAg-positive Chronic Hepatitis B
(2016) Hepatology — Vol. 63, n° 2, p. 377-387 (2016)
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- 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. 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
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Jonas, M. M., Chang, M.-H., Sokal, E., Schwarz, K. B., Kelly, D., Kim, K., Ling, S. C., Rosenthal, P., Oraseanu, D., Reynolds, L., Thiry, A., & Ackerman, P. (2016). Randomized Controlled Trial of Entecavir Versus Placebo in Children with HBeAg-positive Chronic Hepatitis B. Hepatology, 63(2), 377-387. https://doi.org/10.1002/hep.28015 (Original work published 2016)