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).

Abstract

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 NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B 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 (SVR12). 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 SVR12 [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 SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807].

• Authors: M Buti, J L Calleja, S Lens, M Diago, E Ortega, J Crespo, R Planas, M Romero-Gómez, F G Rodríguez, J M Pascasio, B Fevery, D Kurland, C Corbett, R Kalmeijer, W Jessner
• Journal: Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 45 Issue 3 Pg. 468-475 (02 2017) ISSN: 1365-2036 [Electronic] England
• PMID: 27896822 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Interferon-alpha
• Ribavirin
• Simeprevir
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects)
• Carcinoma, Hepatocellular (drug therapy, virology)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Interferon-alpha (therapeutic use)
• Liver Neoplasms (drug therapy, virology)
• Male
• Middle Aged
• Ribavirin (therapeutic use)
• Simeprevir (administration & dosage, adverse effects)
• Sofosbuvir (administration & dosage, adverse effects)
• Sustained Virologic Response
• Treatment Outcome