title: The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection.
abstract: No all-oral, direct-acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a phase 2, multicenter, open-label study to evaluate the efficacy and safety of ledipasvir-sofosbuvir in adolescents with chronic HCV genotype 1 infection. One hundred patients aged 12-17 years received a combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks. On the tenth day following initiation of dosing, 10 patients underwent an intensive pharmacokinetic evaluation of the concentrations of sofosbuvir, ledipasvir, and the sofosbuvir metabolite GS-331007. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at 12 weeks posttreatment. Median age of patients was 15 years (range 12-17). A majority (80%) were HCV treatment-naive, and 84% were infected through perinatal transmission. One patient had cirrhosis, and 42 did not; in 57 patients the degree of fibrosis was unknown. Overall, 98% (98/100; 95% confidence interval 93%-100%) of patients reached sustained virologic response at 12 weeks. No patient had virologic failure. The 2 patients who did not achieve sustained virologic response at 12 weeks were lost to follow-up either during or after treatment. The three most commonly reported adverse events were headache (27% of patients), diarrhea (14%), and fatigue (13%). No serious adverse events were reported. Area under the concentration-time curve (tau) and maximum concentration values for sofosbuvir, ledipasvir, and GS-331007 were within the predefined pharmacokinetic equivalence boundaries of 50%-200% when compared with adults from phase 2 and 3 studies of ledipasvir and sofosbuvir.
  
  
  
  Ledipasvir-sofosbuvir was highly effective at treating adolescents with chronic HCV genotype 1 infection; the dose of ledipasvir-sofosbuvir currently used in adults was well tolerated in adolescents and had an appropriate pharmacokinetic profile. (Hepatology 2017;66:371-378).
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: William F
authors.initials: WF
authors.lastname: Balistreri
authors.affiliation: Seattle Children's Hospital, Seattle, WA.
authors.forename: Karen F
authors.initials: KF
authors.lastname: Murray
authors.affiliation: University of California San Francisco, San Francisco, CA.
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.affiliation: Kings College Hospital, London, UK.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bansal
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Chuan-Hao
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kersey
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Bittoo
authors.initials: B
authors.lastname: Kanwar
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Polina
authors.initials: P
authors.lastname: German
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Evguenia
authors.initials: E
authors.lastname: Svarovskaia
authors.affiliation: Gilead Sciences, Inc., Foster City, CA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Wen
authors.affiliation: University of Florida College of Medicine and Shands Children's Hospital, Gainesville, FL.
authors.forename: Regino P
authors.initials: RP
authors.lastname: Gonzalez-Peralta
authors.affiliation: Boston Children's Hospital, Boston, MA.
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Jonas
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schwarz
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D061214:Patient Safety; D018570:Risk Assessment; D012720:Severity of Illness Index; D000069474:Sofosbuvir / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D004338:Drug Combinations; D005449:Fluorenes; C586541:ledipasvir; D000069474:Sofosbuvir