Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection

Hidenori Toyoda, Kazuaki Chayama, Fumitaka Suzuki, Ken Sato, Tomofumi Atarashi, Tsunamasa Watanabe, Masanori Atsukawa, Atsushi Naganuma, Kazuo Notsumata, Yukio Osaki, Makoto Nakamuta, Koichi Takaguchi, Satoru Saito, Koji Kato, David Pugatch, Margaret Burroughs, Rebecca Redman, Katia Alves, Tami J Pilot-Matias, Rajneet K Oberoi, Bo Fu, Hiromitsu Kumada, Hidenori Toyoda, Kazuaki Chayama, Fumitaka Suzuki, Ken Sato, Tomofumi Atarashi, Tsunamasa Watanabe, Masanori Atsukawa, Atsushi Naganuma, Kazuo Notsumata, Yukio Osaki, Makoto Nakamuta, Koichi Takaguchi, Satoru Saito, Koji Kato, David Pugatch, Margaret Burroughs, Rebecca Redman, Katia Alves, Tami J Pilot-Matias, Rajneet K Oberoi, Bo Fu, Hiromitsu Kumada

Abstract

Glecaprevir (nonstructural protein 3/4A protease inhibitor) and pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-acting antiviral regimen, was evaluated for safety and efficacy in hepatitis C virus genotype 2 (GT2)-infected Japanese patients, including those with compensated cirrhosis. CERTAIN-2 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in treatment-naive and interferon ± RBV treatment-experienced Japanese patients without cirrhosis but with GT2 infection. Patients were randomized 2:1 to receive 8 weeks of G/P (arm A) or 12 weeks of sofosbuvir (400 mg once daily) + RBV (600-1000 mg weight-based, twice daily) (arm B). The primary endpoint was noninferiority of G/P compared to sofosbuvir + RBV by assessing sustained virologic response at posttreatment week 12 (SVR12) among patients in the intent-to-treat population. SVR12 was also assessed in treatment-naive and interferon ± RBV treatment-experienced patients with GT2 infection and compensated cirrhosis who received G/P for 12 weeks in the CERTAIN-1 study. A total of 136 patients were enrolled in CERTAIN-2. SVR12 was achieved by 88/90 (97.8%) patients in arm A and 43/46 (93.5%) patients in arm B. No patient in arm A experienced virologic failure, while 2 did in arm B. The primary endpoint was achieved. In CERTAIN-1, 100% (18/18) of GT2-infected patients with compensated cirrhosis achieved SVR12. Treatment-emergent serious adverse events were experienced by 2 patients without cirrhosis in each arm and no patient with cirrhosis. Conclusion: The results demonstrate high efficacy and favorable tolerability of G/P in GT2-infected Japanese patients. (Hepatology 2018;67:505-513).

Trial registration: ClinicalTrials.gov NCT02723084 NCT02707952.

© 2017 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Figures

Figure 1
Figure 1
Study design for GT2‐infected DAA‐naive patients enrolled in the CERTAIN‐2 study and a subset of patients (GT2‐infected patients with compensated cirrhosis) enrolled in the CERTAIN‐1 arm C study.
Figure 2
Figure 2
SVR12 rates for each arm in the ITT and mITT populations. Error bars represent the 95% CIs. Arm A: 8‐week G/P treatment; arm B: 12‐week SOF + RBV treatment; arm C: 12‐week G/P treatment. *GT2 patients with compensated cirrhosis from CERTAIN‐1 substudy 2.

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