A previous phase IIa study found that the combination of AL-335, odalasvir and simeprevir for 6 or 8 weeks is both efficacious and safe in patients without cirrhosis chronically infected with hepatitis C virus (HCV) genotype (GT)-1. The authors conducted a phase 2b randomised, open-label study to enrol treatment-naïve and interferon (±ribavirin) treatment-experienced patients with HCV GT1, 2, 4, 5 or 6 infection. Patients with HCV GT3 infection and/or liver cirrhosis were excluded. All patients received AL-335 800 mg, odalasvir 25 mg and simeprevir 75 mg OD for 6 or 8 weeks. The primary endpoint was a sustained virologic response 12 weeks following the end of treatment (SVR12). 365 patients (GT1a 29.3%, GT1b 42.5%, GT2 12.3%, GT4 14.2%, GT5 1.4%, GT6 0%) were randomised to receive 6 (n = 183) or 8 weeks (n = 182) of therapy. SVR12 rates after 6 weeks (98.9%) or 8 weeks (97.8%) of treatment were non-inferior compared with a historical control (98%). Viral relapse occurred in five patients (four with HCV GT2c and one with GT1a). All patients, bar four in the 8-week group, that achieved SVR12 also achieved SVR24. One GT1a-infected patient experienced late viral relapse after achieving SVR18. Most of the adverse events (AEs) were mild, with no treatment-related serious AEs seen. Therefore, both 6 and 8 weeks of treatment with AL-335, odalasvir and simeprevir resulted in SVR12 rates of 98.9% and 97.8%, respectively, and was well-tolerated.
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