University of Washington and Seattle Children's Hospital, Seattle, Washington, USA.
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Kings College Hospital, London, United Kingdom.
Cook Children's Health Care System, Fort Worth, Texas, USA.
Auckland Clinical Studies, and Starship Child Health, Auckland, New Zealand.
University of Florida College of Medicine and Shands Children's Hospital, Gainesville, Florida, USA.
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Gilead Sciences, Inc, Foster City, California, USA.
The Mount Sinai Hospital, New York, New York, USA.
Monroe Carell, Jr. Children's Hospital at Vanderbilt, Nashville,, Tennessee, USA.
Boston Children's Hospital, Boston, Massachusetts, USA.
Children's Hospital Los Angeles, Los Angeles, California, USA.
University of Colorado, School of Medicine, and Children's Hospital of Colorado, Aurora, Colorado, USA.
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
University of California San Francisco, San Francisco, California, USA.
Currently, there are no interferon-free treatments available for HCV-infected patients younger than 12 years of age. We evaluated the safety and effectiveness of the all-oral regimen ledipasvir-sofosbuvir ± ribavirin, in HCV-infected children aged 6 to <12 years. In an open-label study, patients aged 6 to <12 years received ledipasvir 45 mg- sofosbuvir 200 mg as two fixed-dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. 92 patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6-11). Most were perinatally infected (97%) and treatment-naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92, 95% CI 94-100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had 3 serious adverse events: tooth abscess, abdominal pain, and gastroenteritis, which were considered to be not related to study treatment. The area under the concentration-time curve and maximum concentration values for sofosbuvir, its primary metabolite GS-331007, and ledipasvir, were within predefined pharmacokinetic equivalence boundaries (50%-200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies.
Ledipasvir-sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.