Journal Article

The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study

Okanoue, Takeshi, Yatsuzuka, Naoyoshi, Caro, Luzelena, Mochida, Satoshi, Iwasa, Takashi, Fujimoto, Go, Wahl, Janice, Kawada, Norifumi, Suzuki, Yoshiyuki, Toyoda, Hidenori, Kumada, Hiromitsu, Yoshiji, Hitoshi, Takaki, Shintaro, Chayama, Kazuaki, Black, Stuart, Itoh, Yoshito, Yodoya, Etsuo, Karino, Yoshiyasu, Robertson, Michael N.

2017

Overview

Background Elbasvir (EBR) in combination with grazoprevir (GZR) has demonstrated efficacy in patients with hepatitis C virus (HCV) infections in trials primarily conducted in the USA and Europe. We investigated the safety and efficacy of EBR in combination with GZR in Japanese patients with chronic HCV infection, with or without cirrhosis. Methods The study was conducted in two parts. In part 1, noncirrhotic patients were randomized 1:1 to receive EBR (50 mg) in combination with GZR (50 or 100 mg) once daily for 12 weeks. In part 2, noncirrhotic patients were randomized 3:1 to receive immediate or deferred treatment with EBR (50 mg) and GZR (100 mg, determined in part 1) for 12 weeks; cirrhotic patients received open-label immediate treatment. The primary efficacy end point was the rate of sustained virologic response 12 weeks after completion of the study treatment. Results In part 1, 63 patients were randomized to receive EBR in combination with GZR at a dose of 50 mg ( n  = 31) or 100 mg ( n  = 32). The SVR12 rates were 100% with GZR at a dose of 50 mg and 96.8% with GZR at a dose of 100 mg. Tolerability was similar in both arms. In part 2, 301 noncirrhotic patients were randomized to receive immediate treatment ( n  = 227) or deferred treatment ( n  = 74), and 35 cirrhotic patients were enrolled. The SVR12 rates were 96.5% and 97.1% after immediate treatment in noncirrhotic and cirrhotic patients respectively. Safety was generally similar between immediate and deferred treatment. Conclusion Treatment with EBR in combination with GZR for 12 weeks is effective and well tolerated in Japanese patients with chronic HCV infection. ClinicalTrials.gov identifier NCT02203149.

• Publisher: Springer Japan,Springer,Springer Nature B.V
• Subject: Abdominal Surgery / Administration, Oral / Adult / Aged / Aged, 80 and over / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / Antiviral Agents - blood / Antiviral Agents - therapeutic use / Benzofurans - administration & dosage / Benzofurans - adverse effects / Benzofurans - blood / Benzofurans - therapeutic use / Biliary Tract / Care and treatment / Colorectal Surgery / Double-Blind Method / Drug Administration Schedule / Drug Resistance, Viral / Drug Therapy, Combination / Female / Gastroenterology / Health aspects / Hepacivirus - drug effects / Hepacivirus - genetics / Hepacivirus - isolation & purification / Hepatitis C virus / Hepatitis C, Chronic - blood / Hepatitis C, Chronic - complications / Hepatitis C, Chronic - drug therapy / Hepatitis C, Chronic - virology / Hepatology / Humans / Imidazoles - administration & dosage / Imidazoles - adverse effects / Imidazoles - blood / Imidazoles - therapeutic use / Infection / Liver cirrhosis / Liver Cirrhosis - drug therapy / Liver Cirrhosis - virology / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / Original Article—Liver / Original —Liver, Pancreas, and Biliary Tract / Pancreas / Quinoxalines - administration & dosage / Quinoxalines - adverse effects / Quinoxalines - blood / Quinoxalines - therapeutic use / RNA, Viral - blood / Surgical Oncology / Sustained Virologic Response / Treatment Outcome / Young Adult