Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis

OPTIMIST-1, a phase 3, randomized study

Paul Kwo, Norman Gitlin, Ronald Nahass, David Bernstein, Kyle Etzkorn, Sergio Rojter, Eugene Schiff, Mitchell Davis, Peter Ruane, Ziad Younes, Ronald Kalmeijer, Rekha Sinha, Monika Peeters, Oliver Lenz, Bart Fevery, Guy De La Rosa, Jane Scott, James Witek

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380).

Original languageEnglish (US)
Pages (from-to)370-380
Number of pages11
JournalHepatology
Volume64
Issue number2
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

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Hepacivirus
Fibrosis
Genotype
Therapeutics
Sofosbuvir
Simeprevir
Confidence Intervals
Gastroenterology
Nausea
Antiviral Agents
Fatigue
Headache
History
Safety

ASJC Scopus subject areas

  • Medicine(all)
  • Hepatology

Cite this

Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis : OPTIMIST-1, a phase 3, randomized study. / Kwo, Paul; Gitlin, Norman; Nahass, Ronald; Bernstein, David; Etzkorn, Kyle; Rojter, Sergio; Schiff, Eugene; Davis, Mitchell; Ruane, Peter; Younes, Ziad; Kalmeijer, Ronald; Sinha, Rekha; Peeters, Monika; Lenz, Oliver; Fevery, Bart; De La Rosa, Guy; Scott, Jane; Witek, James.

In: Hepatology, Vol. 64, No. 2, 01.08.2016, p. 370-380.

Research output: Contribution to journalArticle

Kwo, P, Gitlin, N, Nahass, R, Bernstein, D, Etzkorn, K, Rojter, S, Schiff, E, Davis, M, Ruane, P, Younes, Z, Kalmeijer, R, Sinha, R, Peeters, M, Lenz, O, Fevery, B, De La Rosa, G, Scott, J & Witek, J 2016, 'Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study', Hepatology, vol. 64, no. 2, pp. 370-380. https://doi.org/10.1002/hep.28467
Kwo, Paul ; Gitlin, Norman ; Nahass, Ronald ; Bernstein, David ; Etzkorn, Kyle ; Rojter, Sergio ; Schiff, Eugene ; Davis, Mitchell ; Ruane, Peter ; Younes, Ziad ; Kalmeijer, Ronald ; Sinha, Rekha ; Peeters, Monika ; Lenz, Oliver ; Fevery, Bart ; De La Rosa, Guy ; Scott, Jane ; Witek, James. / Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis : OPTIMIST-1, a phase 3, randomized study. In: Hepatology. 2016 ; Vol. 64, No. 2. pp. 370-380.
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abstract = "Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97{\%} [150/155; 95{\%} confidence interval 94{\%}-100{\%}]) was superior to the historical control (87{\%}). SVR12 with simeprevir+sofosbuvir for 8 weeks (83{\%} [128/155; 95{\%} confidence interval 76-89{\%}]) was not superior to the historical control (83{\%}). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15{\%} [23/155], 14{\%} [22/155], and 12{\%} [19/155]; 8-week arm: 9{\%} [14/155], 17{\%} [26/155], and 15{\%} [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1{\%}, 12-week arm) and three (2{\%}, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380).",
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T1 - Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis

T2 - OPTIMIST-1, a phase 3, randomized study

AU - Kwo, Paul

AU - Gitlin, Norman

AU - Nahass, Ronald

AU - Bernstein, David

AU - Etzkorn, Kyle

AU - Rojter, Sergio

AU - Schiff, Eugene

AU - Davis, Mitchell

AU - Ruane, Peter

AU - Younes, Ziad

AU - Kalmeijer, Ronald

AU - Sinha, Rekha

AU - Peeters, Monika

AU - Lenz, Oliver

AU - Fevery, Bart

AU - De La Rosa, Guy

AU - Scott, Jane

AU - Witek, James

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380).

AB - Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380).

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