Eric Lawitz1, Nancy Reau2, Federico Hinestrosa3, Mordechai Rabinovitz4, Eugene Schiff5, Aasim Sheikh6, Ziad Younes7, Robert Herring8, K Rajender Reddy9, Tram Tran10, Michael Bennett11, Ronald Nahass12, Jenny C Yang13, Sophia Lu13, Hadas Dvory-Sobol13, Luisa M Stamm13, Diana M Brainard13, John G McHutchison13, Brian Pearlman14, Mitchell Shiffman15, Trevor Hawkins16, Michael Curry17, Ira Jacobson18. 1. Texas Liver Institute, University of Texas Health Sciences Center, San Antonio, Texas. Electronic address: lawitz@txliver.com. 2. Rush University Medical Center, Chicago, Illinois. 3. Orlando Immunology Center, Orlando, Florida. 4. University of Pittsburgh, Pittsburgh, Pennsylvania. 5. Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida. 6. Gastrointestinal Specialists of Georgia, Marietta, Georgia. 7. GastroOne, Germantown, Tennessee. 8. Quality Medical Research Center, Nashville, Tennessee. 9. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 10. Sinai Medical Center, Los Angeles, California. 11. Medical Associates Research Group, Inc, San Diego, California. 12. Infectious Disease Care, Hillsborough, New Jersey. 13. Gilead Sciences, Foster City, California. 14. Atlanta Medical Center, Atlanta, Georgia. 15. The Liver Institute of Virginia, Richmond, Virginia. 16. Southwest CARE Center, Santa Fe, New Mexico. 17. Beth Israel Deaconess Medical Center, Boston, Massachusetts. 18. Mount Sinai Beth Israel, New York, New York.
Abstract
BACKGROUND & AIMS: The best regimen to re-treat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus genotype 1 infection. METHODS: We performed an open-label trial at 32 sites in the United States and at 2 sites in New Zealand of 197 patients with genotype 1 hepatitis C virus infection, with or without compensated cirrhosis, who were treatment-naive or were treated previously with a DAA. Between March 2, 2015, and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for 1 treatment group consisting of treatment-naive patients with cirrhosis. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: Among treatment-naive patients without cirrhosis, 71% (24 of 34; 95% confidence interval [CI], 53-85) achieved SVR12 after 6 weeks of treatment and 100% (36 of 36; 95% CI, 90%-100%) achieved SVR12 after 8 weeks of treatment. Among treatment-naive patients with cirrhosis, 94% (31 of 33; 95% CI, 80-99) achieved SVR12 after 8 weeks of treatment and 81% (25 of 31; 95% CI, 63-93) achieved SVR12 after 8 weeks of treatment with ribavirin. Among DAA-experienced patients treated for 12 weeks, 100% without cirrhosis (31 of 31; 95% CI, 89-100) and 100% with cirrhosis (32 of 32; 95% CI, 89-100) achieved SVR12. The most common adverse events were headache, diarrhea, fatigue, and nausea. One patient (<1%) discontinued treatment because of adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found 8 weeks of treatment with sofosbuvir-velpatasvir plus GS-9857 to be safe and effective in treatment-naive patients; 12 weeks was safe and effective in patients previously treated with DAAs. The combination was safe and effective in patients with or without compensated cirrhosis. Clinicaltrials.gov no: NCT02378935.
BACKGROUND & AIMS: The best regimen to re-treat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus genotype 1 infection. METHODS: We performed an open-label trial at 32 sites in the United States and at 2 sites in New Zealand of 197 patients with genotype 1 hepatitis C virus infection, with or without compensated cirrhosis, who were treatment-naive or were treated previously with a DAA. Between March 2, 2015, and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for 1 treatment group consisting of treatment-naive patients with cirrhosis. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: Among treatment-naive patients without cirrhosis, 71% (24 of 34; 95% confidence interval [CI], 53-85) achieved SVR12 after 6 weeks of treatment and 100% (36 of 36; 95% CI, 90%-100%) achieved SVR12 after 8 weeks of treatment. Among treatment-naive patients with cirrhosis, 94% (31 of 33; 95% CI, 80-99) achieved SVR12 after 8 weeks of treatment and 81% (25 of 31; 95% CI, 63-93) achieved SVR12 after 8 weeks of treatment with ribavirin. Among DAA-experienced patients treated for 12 weeks, 100% without cirrhosis (31 of 31; 95% CI, 89-100) and 100% with cirrhosis (32 of 32; 95% CI, 89-100) achieved SVR12. The most common adverse events were headache, diarrhea, fatigue, and nausea. One patient (<1%) discontinued treatment because of adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found 8 weeks of treatment with sofosbuvir-velpatasvir plus GS-9857 to be safe and effective in treatment-naive patients; 12 weeks was safe and effective in patients previously treated with DAAs. The combination was safe and effective in patients with or without compensated cirrhosis. Clinicaltrials.gov no: NCT02378935.
Authors: Tarik Asselah; Christophe Moreno; Christoph Sarrazin; Michael Gschwantler; Graham R Foster; Antonio Craxí; Peter Buggisch; Faisal Sanai; Ceyhun Bicer; Oliver Lenz; Gino Van Dooren; Catherine Nalpas; Isabelle Lonjon-Domanec; Michael Schlag; Maria Buti Journal: PLoS One Date: 2017-01-05 Impact factor: 3.240
Authors: Elise J Smolders; Anouk M E Jansen; Peter G J Ter Horst; Jürgen Rockstroh; David J Back; David M Burger Journal: Clin Pharmacokinet Date: 2019-10 Impact factor: 6.447
Authors: Peter Ruane; Simone I Strasser; Edward J Gane; Robert H Hyland; Jiang Shao; Hadas Dvory-Sobol; Tram Tran; Luisa M Stamm; Diana M Brainard; Lisa Nyberg; Stephen Shafran Journal: J Viral Hepat Date: 2019-02-27 Impact factor: 3.728