Affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection in low and middle-income countries. STORM-C-1 aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in adults chronically infected with HCV, with or without HIV coinfection.
STORM-C-1 was a two-stage, open-label, phase 2/3 single-arm clinical trial conducted in 13 public hospitals in Malaysia and Thailand. Participants with HCV, aged 18–69 years, without cirrhosis or with compensated cirrhosis (Child-Turcotte-Pugh class A), were eligible to participate, regardless of HCV genotype, HIV infection status or previous interferon-based HCV treatment. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for participants without cirrhosis or 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA Between September 2016, and September 2020, 603 participants were enrolled in STORM-C-1. Of these, 296 (49%) had genotype 3 infection, 162 (27%) had genotype 1a, 81 (13%) had genotype 1b, 61 (10%) had genotype 6 and 3 (<1%) had genotype 2. 238 (39%) had compensated cirrhosis, 192 (32%) had HIV co-infection, and 120 (20%) had received previous interferon-based treatment. SVR12 was achieved by 583/602 (96.8%; 95% CI 95.1- 98.1) participants. Results were comparable for difficult to treat subgroups: 230/238 (96.6%; 95% CI 93.5-98.5) for participants with cirrhosis; 289/296 (97.6%; 95% CI 95.2-99.0) with genotype 3 infection, and 186/192 (96.9%; 95% CI 93.3 to 98.8) with HIV co-infection. 70 Grade 3/4 treatment emergent adverse events occurred in 35 participants; of these, 9 in 5 participants were related to study treatment. There were 42 treatment emergent serious adverse events in 36 participants; only 1 (acute kidney injury) was assessed as possibly related to study treatment (sofosbuvir) by the investigator. Three deaths were reported, occurring after the 24-week post-treatment visit, not related to study treatment. There were no significant drug-drug interactions requiring switching of anti-retroviral therapies. Ravidasvir with sofosbuvir is well tolerated with excellent safety and efficacy in HCV infection, including difficult to treat populations, making it suitable for implementation in public health settings.