Sofosbuvir–velpatasvir in children 3–17 years old with hepatitis C virus infection
EudraCT number: 2016-002446-23. ClinicalTrials.gov identifier: NCT03022981.
Abstract
Background
The safety and efficacy of sofosbuvir–velpatasvir in children aged 3–17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated.
Methods
In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir–velpatasvir 400/100 mg tablet (12–17 years), 200/50 mg low dose tablet or oral granules (3–11 years and ≥17 kg), or 150/37.5 mg oral granules (3–5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group.
Findings
Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3–5-year-olds, 93% (68/73) among 6–11-year-olds, and 95% (97/102) among 12–17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12–17-year-olds; vomiting, cough, and headache in 6–11-year-olds; and vomiting in 3–5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range.
Interpretation
The pangenotypic regimen of sofosbuvir–velpatasvir is highly effective and safe in treating children 3–17 years with chronic HCV infection.
CONFLICT OF INTEREST STATEMENT
Maureen M. Jonas has received research grants from Gilead, AbbVie, and Merck; has served as a consultant (DSMB) for Gilead; and has served as a consultant for Mirum and Vertex. Rene Romero has received research grants from Gilead. Philip Rosenthal has received research grants from Gilead, AbbVie, Merck, Albireo, Mirum, Arrowhead, and Travere; has served as a consultant for Gilead, AbbVie, Albireo, Mirum, Travere, Encoded, Biomarin, Vertex, Dicerna, and Audentes. Chuan-Hao Lin has received research grants from Gilead and Mirum. Gabriella Verucchi has received research grants from Gilead and AbbVie; has served as a consultant for Gilead, AbbVie, and Merck. Jessica Wen has received research grants from Gilead, AbbVie, and Alexion; and has served as a consultant for Gilead. William F. Balistreri has received research grants from Gilead, AbbVie, and Merck; has served as a consultant for Alexion, Albireo, Digestive Care, and Otsuka. Daniel H. Leung has received research grants from AbbVie, Gilead, and Mirum; has served as a consultant for Merck and Gilead. Michael R. Narkewicz has served as a consultant for Vertex; has received research funding from Gilead and AbbVie. Regino P. Gonzalez-Peralta has received research grants from Gilead, Merck, AbbVie, and Mirum; has served on advisory boards for Alexion and Murium; has served on drug monitoring boards for Orphalan and Albireo; and has served on speakers bureau for Mirum and Albireo. Alessandra Mangia has received research grants from Gilead and Merck has served as a consultant for Gilead, Merck, and Intercept. Wikrom Karnsakul has received research grants from Gilead and Albireo. Jiang Shao, Jan de Jong, Bandita Parhy, Anu Osinusi, and Kathryn Kersey are employees of and own stock in Gilead Sciences. Karen F. Murray has received research grants from Gilead; has served as a consultant for Albireo and Gilead. Etienne M. Sokal is the chairman of Promethera Biosciences; has served as a consultant for Novartis. Kathleen B. Schwarz has received research grants from Gilead, has served as a consultant for Mirum, UptoDate, and Gilead. The remaining authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
Gilead Sciences shares anonymized individual patient data upon request or as required by law or regulation with qualified external researchers based on submitted curriculum vitae and reflecting nonconflict of interest. The request proposal must also include a statistician. Approval of such requests is at Gilead Science's discretion and is dependent on the nature of the request, the merit of the research proposed, the availability of the data, and the intended use of the data. Data requests should be sent to [email protected].
