Elbasvir/Grazoprevir in People With Hepatitis C Genotype 1 Infection and Child-Pugh Class B Cirrhosis: The C-SALT Study

Ira M Jacobson, Fred Poordad, Roberto Firpi-Morell, Gregory T Everson, Elizabeth C Verna, Sanhita Bhanja, Peggy Hwang, Luzelena Caro, Michael Robertson, Edgar D Charles, Heather Platt, Ira M Jacobson, Fred Poordad, Roberto Firpi-Morell, Gregory T Everson, Elizabeth C Verna, Sanhita Bhanja, Peggy Hwang, Luzelena Caro, Michael Robertson, Edgar D Charles, Heather Platt

Abstract

Introduction: Treatment options are limited for people infected with hepatitis C virus (HCV) with decompensated liver disease. The C-SALT study assessed elbasvir (EBR) plus grazoprevir (GZR) in individuals with HCV genotype 1 infection and Child-Pugh class B (CP-B) cirrhosis.

Methods: In this 12-week, phase 2, nonrandomized, open-label study (NCT02115321; Protocol MK-5172-059), participants with CP-B cirrhosis received EBR 50 mg plus GZR 50 mg once daily, and a control group of noncirrhotic participants received EBR 50 mg plus GZR 100 mg once daily. The primary endpoint was sustained virologic response 12 weeks after the end of therapy.

Results: Sustained virologic response at 12 weeks after the end of therapy was achieved by 27/30 (90.0%) CP-B participants and 10/10 (100.0%) noncirrhotic participants. Two participants relapsed, and one died during follow-up after having undetectable HCV RNA at the end of treatment. Most CP-B participants had stable or improved model for end-stage liver disease and Child-Pugh scores at follow-up week 12 compared with baseline. There was no significant difference in drug exposure between groups, despite the differing GZR dose. Adverse events occurring in >10% of participants were fatigue (CP-B: 30.0%; noncirrhotic: 30.0%), arthralgia (16.7%; 20.0%), nausea (10.0%; 20.0%), and headache (10.0%; 50.0%). No serious treatment-related adverse events or hepatic events of clinical interest occurred.

Conclusions: EBR 50 mg plus GZR 50 mg once daily for 12 weeks was highly effective and well tolerated in a traditionally hard-to-treat population.

Translational impact: Although EBR plus reduced-dose GZR is not available for people with CP-B cirrhosis, these results complement phase 2/3 trial data and real-world experience with EBR/GZR.

Figures

Figure 1.
Figure 1.
SVR12. SVR, sustained virologic response, SVR12, sustained virologic response at 12 weeks after the end of therapy.
Figure 2.
Figure 2.
SVR12 subgroup analyses. BMI, body mass index; CI, confidence interval; CP, Child-Pugh; FW, follow-up week; HCV, hepatitis C virus; MELD, model of end-stage liver disease; SVR12, sustained virologic response at 12 weeks after the end of therapy. aOne participant (CP score 7) died of progressive liver failure at FW4. bOne participant with a CP score of 8 and 1 participant with a CP score of 9 experienced relapse.
Figure 3.
Figure 3.
Prevalence and impact of NS3 and NS5A RASs in participants with HCV GT1a infection, including both participants with Child-Pugh class B cirrhosis and those without cirrhosis. GT, genotype; HCV, hepatitis C virus; NS3, nonstructural protein 3; NS5a, nonstructural protein 5A; RAS, resistance-associated substitution; SVR12, sustained virologic response at 12 weeks after the end of therapy.

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Source: PubMed

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