Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial

Abstract

Background In low-income and middle-income countries, affordable direct-acting antivirals are urgently needed to treat hepatitis C virus (HCV) infection. The combination of ravidasvir, a pangenotypic non-structural protein 5A (NS5A) inhibitor, and sofosbuvir has shown efficacy and safety in patients with chronic HCV genotype 4 infection. STORM-C-1 trial aimed to assess the efficacy and safety of ravidasvir plus sofosbuvir in a diverse population of adults chronically infected with HCV. Methods STORM-C-1 is a two-stage, open-label, phase 2/3 single-arm clinical trial in six public academic and nonacademic centres in Malaysia and four public academic and non-academic centres in Thailand. Patients with HCV with compensated cirrhosis (Metavir F4 and Child-Turcotte-Pugh class A) or without cirrhosis (Metavir F0-3) aged 18-69 years were eligible to participate, regardless of HCV genotype, HIV infection status, previous interferon-based HCV treatment, or source of HCV infection. Once daily ravidasvir (200 mg) and sofosbuvir (400 mg) were prescribed for 12 weeks for patients without cirrhosis and for 24 weeks for those with cirrhosis. The primary endpoint was sustained virological response at 12 weeks after treatment (SVR12; defined as HCV RNA <12 IU/mL in Thailand and HCV RNA <15 IU/mL in Malaysia at 12 weeks after the end of treatment). This trial is registered with ClinicalTrials. gov, number NCT02961426, and the National Medical Research Register of Malaysia, NMRR-16-747-29183. Findings Between Sept 14, 2016, and June 5, 2017, 301 patients were enrolled in stage one of STORM-C-1. 98 (33%) patients had genotype 1a infection, 27 (9%) had genotype 1b infection, two (1%) had genotype 2 infection, 158 (52%) had genotype 3 infection, and 16 (5%) had genotype 6 infection. 81 (27%) patients had compensated cirrhosis, 90 (30%) had HIV co-infection, and 99 (33%) had received previous interferon-based treatment. The most common treatmentemergent adverse events were pyrexia (35 [12%]), cough (26 [9%]), upper respiratory tract infection (23 [8%]), and headache (20 [7%]). There were no deaths or treatment discontinuations due to serious adverse events related to study drugs. Of the 300 patients included in the full analysis set, 291 (97%; 95% CI 94-99) had SVR12. Of note, SVR12 was reported in 78 (96%) of 81 patients with cirrhosis and 153 (97%) of 158 patients with genotype 3 infection, including 51 (96%) of 53 patients with cirrhosis. There was no difference in SVR12 rates by HIV co-infection or previous interferon treatment.Interpretation In this first stage, ravidasvir plus sofosbuvir was effective and well tolerated in this diverse adult population of patients with chronic HCV infection. Ravidasvir plus sofosbuvir has the potential to provide an additional affordable, simple, and efficacious public health tool for large-scale implementation to eliminate HCV as a cause of morbidity and mortality.

Efficacy and safety of sofosbuvir plus daclatasvir or ravidasvir in patients with COVID‐19: A randomized controlled trial

“…A previous study by Esmat et al 29 showed that a combination of SOF‐RDV in addition to ribavirin was associated with a 95.3% response rate among HCV genotype‐4 patients with or without cirrhosis. This is consistent with the STORM‐C‐1 trial, which reported that SOF‐RDV is efficient and well‐tolerated among different populations suffering from chronic HCV infection with or without comorbidities 30 . A recent molecular docking study suggested that RDV could be a potential antiviral drug against SARS‐CoV‐2 by inhibiting viral 3CLpro 31 .…”

“…This is consistent with the STORM-C-1 trial, which reported that SOF-RDV is efficient and well-tolerated among different populations suffering from chronic HCV infection with or without comorbidities. 30 A recent molecular docking study suggested that RDV could be a potential antiviral drug against SARS-CoV-2 by inhibiting viral 3CLpro. 31 Nevertheless, in our study, we did not observe the superiority of a combination of SOF-RDV versus SOC.…”

Assessing the impact of simplified HCV care on linkage to care amongst high-risk patients at primary healthcare clinics in Malaysia: a prospective observational study

“…This study was also designed to feed eligible RNA positive participants into a clinical trial entitled ‘Open label phase II/III, multicentre trial to assess the efficacy, safety, tolerance and pharmacokinetics of sofosbuvir plus ravidasvir in HCV (+/−HIV) chronically infected adults with no or compensated cirrhosis in Thailand and Malaysia’ (Malaysian Medical Research Ethics Committee, approval number NMRR-16-747-29183, coordinated by DND i , hereafter called the DND i trial). 15 16 …”

“…Following a clinical evaluation, participants were referred for enrolment into the DND i trial. 15 16 If patients were eligible and gave their written informed consent to take part in the DND i trial, they were also initiated on treatment and managed as per the DND i trial. Patients who were not eligible or who did not give consent to participate in the DND i trial were referred to the standard of care, the MOH national programme under which.…”

Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2022 Update

“…2021 was a remarkable year for medical research, highlighted by the global roll out of rapidly developed vaccines for COVID-19, the WHO recommendation of the first vaccine for malaria [ 1 ], clinical evidence of a genetic silencing method for Sickle cell disease [ 2 ], and a vastly improved new treatment for hepatitis C [ 3 ]. These and many other remarkable scientific milestones were achieved under the considerable constraints and limitations imposed by the ongoing global pandemic.…”