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Simeprevir in combination with sofosbuvir in treatment‐naïve and ‐experienced patients with hepatitis C virus genotype 4 infection: a Phase III , open‐label, single‐arm study ( PLUTO )
Author(s) -
Buti M.,
Calleja J. L.,
Lens S.,
Diago M.,
Ortega E.,
Crespo J.,
Planas R.,
RomeroGómez M.,
Rodríguez F. G.,
Pascasio J. M.,
Fevery B.,
Kurland D.,
Corbett C.,
Kalmeijer R.,
Jessner W.
Publication year - 2017
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.13883
Subject(s) - simeprevir , sofosbuvir , medicine , cirrhosis , ribavirin , gastroenterology , hepatitis c virus , adverse effect , hepatitis c , hepatocellular carcinoma , ledipasvir , pegylated interferon , virology , virus
Summary Background Hepatitis C virus ( HCV ) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct‐acting antiviral agents in HCV genotype 4‐infected patients with cirrhosis. Aim To evaluate in the phase III , open‐label, single‐arm PLUTO study the efficacy and safety of 12 weeks of simeprevir ( HCV NS 3/4A protease inhibitor) plus sofosbuvir ( HCV nucleotide‐analogue NS 5B polymerase inhibitor) in treatment‐naïve and (peg)interferon ± ribavirin‐experienced HCV genotype 4‐infected patients, with or without compensated cirrhosis. Methods Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once‐daily and sofosbuvir 400 mg once‐daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment ( SVR 12). Safety was also assessed. Results Forty patients received treatment; the majority were male (73%) and treatment‐experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR 12 [100% (Clopper‐Pearson 95% confidence interval: 91–100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment‐emergent laboratory abnormalities were noted in 2/40 (5%) patients. Conclusions Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR 12 rates of 100% in treatment‐naïve and ‐experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [ NCT 02250807]