Daclatasvir plus asunaprevir plus beclabuvir +/- ribavirin for chronic HCV genotype 1-infected treatment-naive patients

摘要

Background and Aims: This phase-2b study examined the safety and efficacy of an all-oral, interferon-free combination of the NS5A replication complex inhibitor daclatasvir (DCV), the NS3 protease inhibitor asunaprevir (ASV), and the non-nucleoside NS5B polymerase inhibitor beclabuvir (BCV) with or without ribavirin in patients with HCV genotype (GT) 1 infection. Methods: A total of 187 patients received 12 weeks of DCV 30 mg BID plus ASV 200 mg BID and BCV 150 mg BID (n = 86) or 75 mg BID with (n = 21) or without (n = 80) weight-based ribavirin BID. The primary endpoint was HCV RNA <25 IU/ml at post-treatment week 12 (SVR12). Results: Overall, 90% of patients (169/187) in the combined treatment groups achieved SVR on or after post-treatment week 12. SVR rates were similar across subgroups (by mITT analysis), i.e. patients with cirrhosis (88%, 14/16), HCV GT-1a (90%, 137/155), and IL28B non-CC genotype (90%, 115/128). There were no drug-related serious AEs or grade 4 AEs. The most frequently reported AEs were headache, diarrhoea, fatigue and nausea. Addition of ribavirin to DCV + ASV + BCV was associated with decreased haemoglobin, compared with DCV + ASV + BCV alone. There were six grade 3/4 laboratory abnormalities noted, all unrelated to the study drugs. Viral breakthrough occurred in 2.5-4.8% of patients across groups and appeared unrelated to BCV dose or ribavirin inclusion. Conclusions: Results support phase 3 evaluation of a twice-daily, fixed-dose formulation of this DCV + ASV + BCV regimen with or without ribavirin in HCV GT-1-infected patients.