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Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial

2016; Elsevier BV; Volume: 65; Issue: 6 Linguagem: Inglês

10.1016/j.jhep.2016.07.050

1600-0641

Jan Šperl, Gábor Horváth, Waldemar Halota, Juan Arenas Ruiz-Tapiador, Adrian Streinu‐Cercel, Ligita Jančorienė, Klára Werling, Hege Kileng, Seyfettin Köklü, Jan Gerstoft, Petr Urbánek, Robert Flisiak, Rafael Alexander Leiva, Edita Kazėnaitė, R Prinzing, Sushma Patel, Jingjun Qiu, Ernest Asante‐Appiah, Janice Wahl, Bach‐Yen Nguyen, Eliav Barr, Heather Platt,

Liver Disease Diagnosis and Treatment

Background & Aims Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. Methods This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000 IU/ml were randomized to receive 12 weeks of EBR/GZR 50 mg/100 mg once daily (n = 129) or sofosbuvir (400 mg once daily) plus PR (n = 128). Primary efficacy objective was sustained virologic response 12 weeks after the end of therapy (SVR12, HCV RNA <15 IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event. Results The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6–15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than −10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, −35.5% to −19.6%; p 10,000 IU/ml were randomized to receive 12 weeks of EBR/GZR 50 mg/100 mg once daily (n = 129) or sofosbuvir (400 mg once daily) plus PR (n = 128). Primary efficacy objective was sustained virologic response 12 weeks after the end of therapy (SVR12, HCV RNA <15 IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event. The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6–15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than −10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, −35.5% to −19.6%; p <0.001]). EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR.