According to a study published in Hepatology, children with chronic hepatitis C virus (HCV) infection benefitted from an all-oral regimen of ledispasvir–sofosbuvir. Ledispasvir–sofosbuvir was found to be highly effective and well-tolerated in children 6 to <12 years old.
This phase 2, open-label, multi-center study (ClinicalTrials.gov Identifier: NCT02249182) sought to evaluate the efficacy and safety of ledispasvir 45 mg–sofosbuvir 200 mg ± ribavirin to treat children 6 to <12 years old with chronic HCV infection. In addition, investigators performed pharmacokinetic evaluation on a subset of patients after 10 days of ledipasvir–sofosbuvir treatment to determine if exposure was similar to that observed in adults.
The study enrolled 92 patients aged 6 to <12 years diagnosed with chronic infection of HCV genotype 1 (n=88), 3 (n=2), and 4 (n=2). Participants received ledipasvir 45 mg–sofosbuvir 200 mg administered as 2 fixed-dose combination tablets 22.5/100 mg once a day for 12 or 24 weeks. Ribavirin was administered with the dose depending on HCV genotype and cirrhosis status.
The first 12 participants underwent a pharmacokinetic evaluation to confirm dose appropriateness of the ledispasvir–sofosbuvir treatment.
Efficacy was measured as the percentage of patients who achieved sustained virologic response 12 weeks after therapy stopped. Safety factors were evaluated at every visit and included reporting vital signs, adverse events, laboratory test results, and concomitant medication use.
Of the 92 participants, 97% were perinatally infected and 78% were treatment naïve; 35 patients did not have cirrhosis, 2 patients had confirmed cirrhosis, and the degree of fibrosis was unknown in 55 patients. The overall sustained virologic response rate was 99% (91 out of 92; 95% CI, 94%-100%).
The only patient not reaching sustained virologic response was a treatment-naïve female infected with HCV genotype 1a and confirmed cirrhosis. This patient relapsed 4 weeks after completing the 12-week treatment regimen.
The most common adverse events reported by patients were headache (18%), pyrexia (17%), and abdominal pain (15%). Only 1 patient experienced 3 serious adverse events that were moderate in intensity and unrelated to the study treatment. Treatment did not affect pubertal development upon follow up. Pharmacokinetic evaluation revealed that the pediatric doses of sofosbuvir 45 mg and leipasvir 200 mg were within predefined pharmacokinetic equivalence boundaries (50% to 200%) when compared with the values defined for adults in phase 2 or 3 studies.
Limitations of the study included a small study sample with mostly HCV genotype 1 and only 2 patients with cirrhosis. However, the high treatment response and ledispasvir–sofosbuvir exposure were consistent with observations in adults and adolescents.
A fixed-dose combination of ledispasvir and sofosbuvir ± ribavirin was well tolerated and highly effective for treatment-naïve or interferon-experienced children aged 6 to <12 with chronic HCV genotype 1, 3, and 4 infections. The availability of a more tolerable HCV treatment option for children represents an important advancement in pediatric care.
Murray KF, Balistreri WF, Bansal S, et al. Safety and efficacy of ledipasvir-sofosbuvir with or without ribavirin for chronic hepatitis C in children ages 6–11 [published online August 2, 2018]. Hepatology. doi: 10.1002/hep.30123.