title: 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-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Boston Children's Hospital, Boston, MA.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Jonas
authors.affiliation: National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Mei-Hwei
authors.initials: MH
authors.lastname: Chang
authors.affiliation: Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.affiliation: Johns Hopkins Children's Center, Baltimore, MD.
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Schwarz
authors.affiliation: Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Deirdre
authors.initials: D
authors.lastname: Kelly
authors.affiliation: Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Mo
authors.initials: KM
authors.lastname: Kim
authors.affiliation: The Hospital For Sick Children, and Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ling
authors.affiliation: University of California, San Francisco, CA.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.affiliation: Grigore Alexandrescu Emergency Hospital for Children, Bucharest, Romania.
authors.forename: Dumitru
authors.initials: D
authors.lastname: Oraseanu
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Laurie
authors.initials: L
authors.lastname: Reynolds
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Thiry
authors.affiliation: Bristol-Myers Squibb, Wallingford, CT.
authors.forename: Peter
authors.initials: P
authors.lastname: Ackerman
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine