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Clinical Trial
. 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)

Free PMC article
Clinical Trial

Simeprevir Plus Sofosbuvir in Patients With Chronic Hepatitis C Virus Genotype 1 Infection and Cirrhosis: A Phase 3 Study (OPTIMIST-2)

Eric Lawitz et al. Hepatology. .
Free PMC article


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).


Figure 1
Figure 1
Patient disposition. At the time of the primary analysis, 100% of patients had reached SVR12 after the EOT time point or had discontinued earlier. Abbreviation: ITT, intent to treat.
Figure 2
Figure 2
SVR12 by baseline NS5A and Q80K polymorphisms (intent‐to‐treat population).

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    1. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol 2014;61:S58‐S68. - PubMed
    1. Ferenci P. Treatment of hepatitis C in difficult‐to‐treat patients. Nat Rev Gastroenterol Hepatol 2015;12:284‐292. - PubMed
    1. European Association for the Study of the Liver . Clinical practice guidelines: recommendations on treatment of hepatitis C 2015.‐contributions/clinical‐practice‐guidelines/detail/recommendations‐on‐treatment‐of‐hepatitis‐c‐2015. Accessed May 5, 2015.
    1. American Association for the Study of Liver Diseases . HCV guidance: recommendations for testing, managing, and treating hepatitis C.‐report‐view. Accessed May 5, 2015. - PubMed
    1. Kleinman L, Mannix S, Yuan Y, Kummer S, L'Italien G, Revicki D. Review of patient‐reported outcome measures in chronic hepatitis C. Health Qual Life Outcomes 2012;10:92. - PMC - PubMed

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