Details

Autor(en) / Beteiligte

• Gane, Edward J., MD
• Schwabe, Christian, MD
• Hyland, Robert H., DPhil
• Yang, Yin, PhD
• Svarovskaia, Evguenia, PhD
• Stamm, Luisa M., MD, PhD
• Brainard, Diana M., MD
• McHutchison, John G., MD
• Stedman, Catherine A., MBChB, PhD

Titel

Efficacy of the Combination of Sofosbuvir, Velpatasvir, and the NS3/4A Protease Inhibitor GS-9857 in Treatment-naïve or Previously Treated Patients with HCV Genotype 1 or 3 Infections

Ist Teil von

• Gastroenterology (New York, N.Y. 1943), 2016

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract Background & Aims We performed a phase 2 trial of the efficacy and safety of 4, 6, and 8 weeks of sofosbuvir, given in combination with the NS5A inhibitor velpatasvir and the NS3/4A protease inhibitor GS-9857, in patients with hepatitis C virus (HCV) infection. Methods We enrolled 161 treatment-naïve or previously treated patients infected with HCV genotypes 1 or 3 with or without compensated cirrhosis at 2 centers in New Zealand, from September 2014 through March 2015. All patients received sofosbuvir (400 mg) and velpatasvir (100 mg) plus GS-9857 (100 mg) once daily. The primary efficacy endpoint was sustained virologic response at 12 weeks after therapy (SVR12). The duration of therapy was determined by baseline patient characteristics: 4 or 6 weeks for treatment-naïve patients without cirrhosis, 6 weeks for treatment-naïve patients with cirrhosis, and 6 or 8 weeks for treatment-experienced patients with or without cirrhosis. Results Four weeks of sofosbuvir, velpatasvir, and GS-9857 produced an SVR12 in 4/15 (27%) treatment-naïve patients with HCV genotype 1 without cirrhosis. Six weeks of this combination produced a SVR12 in 14/15 (93%) treatment-naïve patients with HCV genotype 1 without cirrhosis, in 13/15 (87%) treatment-naïve genotype 1 patients with cirrhosis, in 15/18 (83%) treatment-naïve patients with HCV genotype 3 with cirrhosis, and in 20/30 (67%) patients with HCV genotype 1 who had failed an all-oral regimen of 2 or more direct-acting antiviral agents (DAAs). Eight weeks of the drug combination produced an SVR12 in 17/17 (100%) patients with HCV genotype 1, in 19/19 (100%) patients with HCV genotype 3 and cirrhosis who had failed peg-interferon plus ribavirin, in 25/28 (89%) patients with HCV genotype 1 who had failed protease inhibitor-based triple therapy, and in 4/4 (100%) patients with HCV genotype 3 who had failed an all-oral regimen of 2 or more DAAs. The most common reported adverse events were headache, nausea, and fatigue. Conclusions Eight weeks of treatment with the combination of sofosbuvir, velpatasvir, and GS-9857 produced an SVR12 in most treatment-naïve or previously treated patients with HCV genotype 1 or 3 infections, including those with compensated cirrhosis. ClinicalTrials.gov number: NCT02202980.