Randomized Controlled Trial of the NS5A Inhibitor Daclatasvir plus Pegylated Interferon and Ribavirin for HCV Genotype-4 (COMMAND-4). Issue 3 (April 2016)

• Record Type: Journal Article
• Authors: Hézode, Christophe; Alric, Laurent; Brown, Ashley; Hassanein, Tarek; Rizzetto, Mario; Buti, Maria; Bourlière, Marc; Thabut, Dominique; Molina, Esther; Rustgi, Vinod; Samuel, Didier; McPhee, Fiona; Liu, Zhaohui; Yin, Philip D; Hughes, Eric; Treitel, Michelle
• Is Part Of: Antiviral therapy. Volume 21:Issue 3(2016)
• Page Start: 195
• Page End: 205
• Publication Date: 2016-04
• Subjects: Antiviral agents -- Periodicals; Antiviral Agents -- therapeutic use; Virus Diseases -- therapy; Viruses -- drug effects; Antiviral agents; Periodical; Electronic journals; Periodicals; 616.9106
• DOI: 10.3851/IMP2985
• Languages: English
• ISSNs: 1359-6535

Abstract

Background: Treatment options for HCV genotype-4 (GT4) are limited. This Phase III study (COMMAND-4; AI444-042) evaluated the efficacy and safety of daclatasvir (DCV), a pan-genotypic HCV NS5A inhibitor, with pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in treatment-naive patients with HCV GT4 infection. Methods: Patients were randomly assigned (2:1; blinded) to treatment with DCV 60 mg ( n =82) or placebo ( n =42) once daily plus PEG-IFN 180 μg weekly and RBV 1, 000–1, 200 mg/ day (weight-based) twice daily. DCV-treated patients with undetectable HCV RNA at weeks 4 and 12 (eRVR) received 24 weeks of DCV plus PEG-IFN/RBV; those without eRVR received an additional 24 weeks of PEG-IFN/RBV. All placebo-treated patients received 48 weeks of PEG-IFN/RBV. The primary end point was sustained virological response (SVR) at post-treatment week 12 (SVR12). Results: Patients were 75% IL28B non-CC and 11% had cirrhosis. SVR rates (HCV RNA < lower limit of quantitation [LLOQ]) at post-treatment week 12 or later (imputed to include patients missing SVR12 assessments but had SVR after post-treatment week 12) were 82% (67/82) with DCV plus PEG-IFN/RBV versus 43% (18/42) with PEG-IFN/RBV ( P <0.0001). In DCV recipients, SVR12 rates were comparable across subgroups. The safety and tolerability profile of DCV plus PEG-IFN/RBV was comparable to that of PEG-IFN/RBV. Discontinuations due to adverse events occurred in 4.9% of patients receiving DCV plus PEG-IFN/RBV and 7.1% of patients receiving PEG-IFN/RBV. Conclusions: In treatment-naive patients with HCV GT4 infection, DCV plus PEG-IFN/RBV achieved higher SVR12 rates than PEG-IFN/RBV alone. These data support DCV-based regimens for treatment of HCV GT4 infection, including all-oral combinations with other direct-acting antivirals (AI444-042; ClinicalTrials.gov NCT01448044).