No all-oral, direct-acting antiviral regimens have been approved for children with chronic hepatitis C virus (HCV) infection. We conducted a Phase 2, multi-center, open-label study to evaluate the efficacy and safety of ledipasvir–sofosbuvir in adolescents with chronic HCV genotype 1 infection. One hundred patients ages 12 to 17 years received a combination tablet of 90 mg ledipasvir and 400 mg sofosbuvir once daily for 12 weeks. On the 10th 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 12 weeks posttreatment (SVR12). Median age of patients was 15 years (range, 12-17 years). A majority (80%) were HCV treatment naïve, 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% CI, 93% to 100%) of patients reached SVR12. No patient had virologic failure. The 2 patients who did not achieve SVR12 were lost to follow-up either during or after treatment. The 3 most commonly reported adverse events were headache (27% of patients), diarrhea (14%), and fatigue (13%). No serious adverse events were reported. AUCtau and Cmax values for sofosbuvir, ledipasvir, and GS-331007 were within the predefined pharmacokinetic equivalence boundaries of 50% to 200% when compared with adults from Phase 2 and 3 studies of ledipasvir and sofosbuvir.
Conclusion: Ledipasvir−sofosbuvir was highly effective in 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. This article is protected by copyright. All rights reserved.