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

Maureen M. Jonas, Mei Hwei Chang, Etienne Sokal, Kathleen B. Schwarz, Deirdre Kelly, Kyung Mo Kim, Simon C. Ling, Philip Rosenthal, Dumitru Oraseanu, Laurie Reynolds, Alexandra Thiry, Peter Ackerman

Research output: Contribution to journalArticle

Abstract

This ongoing, randomized phase III study assesses the safety and efficacy of entecavir versus placebo in nucleos(t)ide-naïve 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] vs. 3.3% [2 of 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 of 120] vs. 3.3% [2 of 60]; P<0.0001); alanine aminotransferase normalization (67.5% [81 of 120] vs. 23.3% [14 of 60]; P<0.0001); and HBeAg seroconversion (24.2% [29 of 120] vs. 10.0% [6 of 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 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.

Original languageEnglish (US)
Pages (from-to)377-387
Number of pages11
JournalHepatology
Volume63
Issue number2
DOIs
StatePublished - Feb 1 2016

ASJC Scopus subject areas

  • Hepatology

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    Jonas, M. M., Chang, M. H., Sokal, E., Schwarz, K. B., Kelly, D., Kim, K. M., Ling, S. C., Rosenthal, P., Oraseanu, D., Reynolds, L., Thiry, A., & Ackerman, P. (2016). Randomized, controlled trial of entecavir versus placebo in children with hepatitis B envelope antigen-positive chronic hepatitis B. Hepatology, 63(2), 377-387. https://doi.org/10.1002/hep.28015