Pharmacokinetics, Safety, Efficacy and Acceptability of Daclatasvir Plus Sofosbuvir in Young Children With Chronic HCV Infection.

BACKGROUND AND AIMS: Sofosbuvir (SOF) plus daclatasvir (DCV) is a primary chronic hepatitis C virus (HCV) treatment in low- and middle-income countries. WHO guidelines recommend a half-adult dose for children (14-25 kg) based on pharmacokinetic modelling, requiring clinical validation. We evaluated the pharmacokinetics, safety, efficacy and acceptability of DCV (30 mg) and SOF (200 mg) in children weighing 14 to < 17 kg and 17-35 kg.

METHODS

Children (3-13 years; 14-35 kg) with chronic HCV received a daily paediatric formulation of DCV 30 mg and SOF 200 mg for 12 weeks. Intensive steady-state PK sampling was performed. Efficacy was assessed by sustained virologic response at 12 weeks post-treatment (SVR12), and adverse events were monitored.

RESULTS

Twenty-three patients were enrolled in two groups: 14 to < 17 kg (n = 11; median age 5 [3-8] years) and 17-35 kg (n = 12; median age 7 [5-13] years). For children 14 to < 17 kg, mean (CV%) AUC24 (ng·h/mL) and Cmaxss (ng/mL) were 14 875 (55) and 1604 (48) for DCV; 2683 (65) and 1562 (69) for SOF; and 10 456 (77) and 1420 (84) for GS-331007. For children 17-35 kg, values were 11 082 (47) and 1062 (32) for DCV; 2125 (88) and 952 (61) for SOF; and 15 256 (27) and 1606 (46) for GS-331007. All patients achieved SVR12, with good acceptability and no serious adverse events.

CONCLUSIONS

For children 14-35 kg with chronic HCV, half the adult dose of DCV (30 mg) and SOF (200 mg) offered comparable exposure, safety, efficacy and acceptability to the adult regimen.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT0585451.