Efficacy and Safety of Sofosbuvir/Velpatasvir Plus Ribavirin in Patients with Hepatitis C Virus-Related Decompensated Cirrhosis

Abstract

A fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) plus weight-based ribavirin (RBV) for 12 weeks is recommended for the treatment of patients with hepatitis C virus (HCV)-associated decompensated cirrhosis. However, large global studies, while confirming the effectiveness of SOF/VEL in a broad range of patients, often exclude these patients. This Phase 2, single-arm, open-label study in adult patients with HCV-associated decompensated cirrhosis in France and the USA aimed to provide further data on the safety and efficacy of SOF/VEL plus RBV for 12 weeks in this population. Patients were treated with a fixed-dose combination of SOF 400 mg/VEL 100 mg plus weight-based RBV once daily for 12 weeks. The inclusion criteria were chronic HCV infection (≥6 months), quantifiable HCV RNA at screening, Child-Turcotte-Pugh class B or C cirrhosis, and liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma. Among 32 patients who initiated treatment, 78.1% achieved sustained virologic response 12 weeks after the end of treatment (SVR12). Failure to achieve SVR12 was due to non-virologic reasons (investigator discretion, n = 1; death, n = 6). All 25 patients in the per-protocol population achieved SVR12 and all but one achieved sustained virologic response 24 weeks after the end of treatment. Adverse events (AEs) were as expected for a patient population with advanced liver disease. All Grade 3-4 and serious AEs and deaths were deemed unrelated to treatment. In patients with HCV-associated decompensated cirrhosis, SOF/VEL plus RBV achieved high SVR12 rates and was generally well tolerated.

Keywords: HCV; decompensated cirrhosis; ribavirin; sofosbuvir/velpatasvir; sustained virologic response.

Figure 1

Patient characteristics (screened subjects). SVR12, sustained virologic response 12 weeks after the end of treatment; SVR24, sustained virologic response 24 weeks after the end of treatment.

Figure 2

Percentage of patients achieving SVR12 overall and by subgroup (ITT analysis). The rates of SVR12 overall and by subgroup are shown. The viral load of two subjects included in the overall population was too low to assess genotype. The I bars represent 95% confidence intervals. CTP, Child–Turcotte–Pugh; ITT, intent-to-treat; GT, genotype; SVR12, sustained virologic response 12 weeks after the end of treatment.

Figure 3

Change in CTP score (baseline to Week 24 in patients with SVR24 and liver function data available, n = 19). The changes in CTP score are shown from baseline to Week 24 in patients with SVR24 who had baseline and Week 24 data available and did not undergo liver transplant. CTP, Child–Turcotte–Pugh; SVR24, sustained virologic response 24 weeks after the end of treatment.

Figure 3

Change in CTP score (baseline to Week 24 in patients with SVR24 and liver function data available, n = 19). The changes in CTP score are shown from baseline to Week 24 in patients with SVR24 who had baseline and Week 24 data available and did not undergo liver transplant. CTP, Child–Turcotte–Pugh; SVR24, sustained virologic response 24 weeks after the end of treatment.

Figure 4

Change in MELD score (baseline to Week 24 in patients with SVR24 and liver function data available, n = 19). The changes in MELD score from baseline to Week 24 are shown in patients with SVR24 who had baseline and Week 24 data available and did not undergo liver transplant. MELD, Model for End-stage Liver Disease; SVR24, sustained virologic response 24 weeks after the end of treatment.

Figure 4

Change in MELD score (baseline to Week 24 in patients with SVR24 and liver function data available, n = 19). The changes in MELD score from baseline to Week 24 are shown in patients with SVR24 who had baseline and Week 24 data available and did not undergo liver transplant. MELD, Model for End-stage Liver Disease; SVR24, sustained virologic response 24 weeks after the end of treatment.