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Hepatology. 2016 Aug;64(2):360-9. doi: 10.1002/hep.28422. Epub 2016 Feb 19.

Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST-2).

Author information

1
Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX.
2
The Gastroenterology Group of South Jersey, Vineland, NJ.
3
Orlando Immunology Center, Orlando, FL.
4
University of British Columbia, Vancouver, BC, Canada.
5
Private practice, Bakersfield, CA.
6
Texas Clinical Research Institute, Arlington, TX.
7
University Hepatitis Center at Pointe West Infectious Diseases, Bradenton, FL.
8
Quality Medical Research, Nashville, TN.
9
Digestive Health Specialists, Winston-Salem, NC.
10
Gastrointestinal Specialists of Georgia, Marietta, GA.
11
Concorde Medical Group, New York, NY.
12
South Denver Gastroenterology, P.C., Denver, CO.
13
Janssen Research & Development LLC, Titusville, NJ.
14
Janssen Pharmaceutica NV, Beerse, Belgium.
15
Janssen Global Services LLC, Titusville, NJ.
16
Janssen Global Services LLC, High Wycombe, UK.

Abstract

Hepatitis C virus (HCV)-infected patients with cirrhosis are historically a difficult-to-treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1-infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open-label, single-arm study (OPTIMIST-2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1-infected treatment-naive or treatment-experienced patients with cirrhosis. Patients (aged 18-70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient-reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%-91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment-naive and treatment-experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient-reported outcomes improved from baseline to follow-up week 12.

CONCLUSION:

Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment-naive and treatment-experienced HCV GT1-infected patients with cirrhosis and was generally safe and well tolerated. (Hepatology 2016;64:360-369).

PMID:
26704148
PMCID:
PMC5297873
DOI:
10.1002/hep.28422
[Indexed for MEDLINE]
Free PMC Article

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