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 C_maxss (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