Short‐duration treatment for chronic hepatitis C virus with daclatasvir, asunaprevir, beclabuvir and sofosbuvir (FOURward study)

Background & Aims The phase 2, FOURward study (NCT02175966) investigated short‐duration therapy (4/6 weeks) with four direct‐acting antivirals (DAAs) with distinct mechanisms of action in patients infected with hepatitis C virus (HCV) genotype‐1. Methods Non‐cirrhotic patients were randomized 1:1 to DCV‐TRIO (fixed‐dose daclatasvir 30 mg, asunaprevir 200 mg and beclabuvir 75 mg) twice‐daily + sofosbuvir 400 mg once‐daily for 4 or 6 weeks. The primary endpoint was sustained virological response at post‐treatment Week 12 (SVR12). Patients without SVR12 were offered retreatment based on the DAA resistance profile at failure; patients with resistance to ≤1 DCV‐TRIO component received DCV‐TRIO + RBV for 12 weeks. Results Twenty‐eight patients with HCV genotype‐1 were enrolled; 79% had genotype‐1a infection and median baseline HCV‐RNA levels were high (9 × 106 IU/mL). Most patients had undetectable HCV‐RNA at end of treatment (96% [n=27/28]); however, relapse occurred in 77% (n=10/13) and 43% (n=6/14) treated for 4 and 6 weeks, leading to SVR12 rates of 29% (n=4/14) and 57% (n=8/14) respectively. SVR12 was higher in patients with lower baseline HCV‐RNA (