TY - JOUR
T1 - Sofosbuvir (GS-7977) plus peginterferon/ribavirin in treatment-naïve patients with HCV genotype 1
T2 - A randomized, 28-day, dose-ranging trial
AU - Rodriguez-Torres, Maribel
AU - Lawitz, Eric
AU - Kowdley, Kris V.
AU - Nelson, David R.
AU - Dejesus, Edwin
AU - McHutchison, John G.
AU - Cornpropst, Melanie T.
AU - Mader, Michael
AU - Albanis, Efsevia
AU - Jiang, Deyuan
AU - Hebner, Christy M.
AU - Symonds, William T.
AU - Berrey, Michelle M.
AU - Lalezari, Jay
N1 - Funding Information:
The authors would like to thank the patients and staff who participated in the study. This work was previously presented, in part, at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AALD) October 29–November 02, 2010, Boston MA, USA. This Study was funded by Gilead Sciences, Inc. Dr Severina Moreira from Niche Science and Technology (Richmond-upon-Thames, UK) provided writing and editorial support for the development of this manuscript and was paid for these services by Gilead Sciences, Inc. DRN is supported in part by the NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064.
PY - 2013/4
Y1 - 2013/4
N2 - Background & Aims Sofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-naïve patients infected with genotype 1 HCV. Methods In this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400 mg) or placebo plus PegIFN/RBV for 28 days, after which all patients continued to receive PegIFN/RBV alone for a further 44 weeks. Results Patients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5 log10 IU/ml (-5.3 for 100 mg, -5.1 for 200 mg and -5.3 for 400 mg) vs. -2.8 log10 IU/ml for placebo/PegIFN/RBV after 28 days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94%) than placebo (21%), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56%, 83%, and 80% for sofosbuvir 100, 200, and 400 mg, respectively, vs. 43% for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100 mg group than sofosbuvir 200 and 400 mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea. Conclusions These results support further studies with sofosbuvir at 200 mg and 400 mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.
AB - Background & Aims Sofosbuvir (formerly GS-7977) is a pyrimidine nucleotide analog inhibitor of the hepatitis C virus (HCV) NS5B polymerase. We assessed the safety, tolerability, antiviral activity, and pharmacokinetics of sofosbuvir plus pegylated-interferon (PegIFN)/ribavirin (RBV) in a 28-day, dose-ranging trial in treatment-naïve patients infected with genotype 1 HCV. Methods In this double-blind study, 64 patients were randomized (1:1:1:1) to receive one of three once-daily doses of oral sofosbuvir (100, 200, or 400 mg) or placebo plus PegIFN/RBV for 28 days, after which all patients continued to receive PegIFN/RBV alone for a further 44 weeks. Results Patients in the sofosbuvir/PegIFN/RBV groups experienced mean reductions in HCV RNA >5 log10 IU/ml (-5.3 for 100 mg, -5.1 for 200 mg and -5.3 for 400 mg) vs. -2.8 log10 IU/ml for placebo/PegIFN/RBV after 28 days. Rapid virologic response (RVR) rates were markedly higher after sofosbuvir treatment (88-94%) than placebo (21%), as were rates of sustained virologic response (SVR) at post-treatment Week 24 (56%, 83%, and 80% for sofosbuvir 100, 200, and 400 mg, respectively, vs. 43% for placebo). The number of patients experiencing virologic breakthrough and post-treatment relapse was higher in the sofosbuvir 100 mg group than sofosbuvir 200 and 400 mg groups. Sofosbuvir was well tolerated; the most frequent adverse events were fatigue and nausea. Conclusions These results support further studies with sofosbuvir at 200 mg and 400 mg to determine the optimal dose and treatment duration of sofosbuvir in HCV genotype 1.
KW - Antiviral
KW - Hepatitis C virus
KW - Rapid virologic response
KW - Sofosbuvir
KW - Sustained virologic response
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UR - http://www.scopus.com/inward/citedby.url?scp=84880964894&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2012.11.018
DO - 10.1016/j.jhep.2012.11.018
M3 - Article
C2 - 23183528
AN - SCOPUS:84880964894
SN - 0168-8278
VL - 58
SP - 663
EP - 668
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 4
ER -