Glecaprevir/Pibrentasvir to Treat Chronic Hepatitis C Virus Infection in Asia: Two Multicentre, Phase 3 Studies – A Randomised, Double-Blind Study (VOYAGE-1) and an Open-Label, Single-Arm Study (VOYAGE-2)

Abstract

Background: Glecaprevir/pibrentasvir results in high rates of sustained virological response in patients with chronic hepatitis C virus (HCV) genotype 1-6 infection. Data in non-Japanese Asian patients have been minimal. Methods: Two phase 3 studies were undertaken in treatment-naive and treatment-experienced patients with chronic HCV genotype 1-6 infection: a randomised, double-blind, placebo-controlled study recruited patients without cirrhosis at 47 sites across China, South Korea, and Singapore (VOYAGE-1; NCT03222583); a single-arm, open-label study recruited patients with compensated cirrhosis at 34 sites across China and South Korea (VOYAGE-2; NCT03235349). Glecaprevir/pibrentasvir (300 mg/120 mg) or placebo (VOYAGE-1, 2:1 ratio) was given for 8 or 12 weeks in patients without and with cirrhosis, respectively (16 weeks in treatment-experienced patients with genotype 3). Primary efficacy endpoint was sustained virological response at post-treatment week 12 (SVR12; HCV RNA <15 IU/mL) in the intention-to-treat (ITT) population. Primary objective (VOYAGE-1) was comparison with historical SVR12 rates. Findings: Of 546 patients without cirrhosis enrolled (October 4, 2017-May 16, 2018), one was not treated (ITT: n=545). 352/362 patients who received glecaprevir/pibrentasvir achieved SVR12 (97·2% [95% CI 95·5–98·9]); non-inferiority to a historical SVR12 rate was demonstrated. Of 160 patients with compensated cirrhosis enrolled (September 29, 2017-June 14, 2018) (ITT: n=160), 159/160 achieved SVR12 (99·4% [95% CI 98·2–100·0]). All patients with virological failure (VOYAGE-1: n=8; VOYAGE-2: n=1) were enrolled in China; six had genotype 3b with a history of injection drug use. One patient with cirrhosis discontinued study drug due to an adverse event. Upper respiratory tract infection was the most common adverse event (VOYAGE-1: 35/362 [10%]; VOYAGE-2: 19/160 [12%]). Interpretation: Glecaprevir/pibrentasvir achieved high SVR12 rates and was well tolerated in Asian patients with chronic HCV genotype 1-6 infection, similar to other phase 3 studies. Trial Registration: (VOYAGE-1; NCT03222583), (VOYAGE-2; NCT03235349). Funding Statement: The studies were designed and conducted by the investigators and the sponsor, AbbVie. Declaration of Interests: Lai Wei: Consulting fees for Abbvie, Allergan, Ascletis, Bristol-Myers Squibb, Gilead Sciences, Johnson & Johnson, Novartis, Pfizer and Roche; research grants from Abbvie, Bristol-Myers Squibb, Gilead Sciences and Roche (all for institution) Guiqiang Wang: No conflicts of interest Negar N Alami: Employee of AbbVie and may own stock or share options Wen Xie: No conflicts of interest Jeong Heo: Research support from Roche; advisor for AbbVie, Bristol-Myers Squibb and Gilead Sciences Qing Xie: Nothing to disclose Mingxiang Zhang: Principal investigator: Abbvie Yoon Jun Kim: Consulting fees for AbbVie, Gilead Sciences, Bristol-Myers Squibb, Samil and PharmaKing; research grant support from Roche, Bristol-Myers Squibb, Gilead Sciences, LG Sciences, Hanmi, Ildong, Daewoong, Bayer, Yuhan Seng Gee Lim: Research support from Abbott, Gilead, Merck, and Roche; advisor for Abbott, AbbVie, Arbutus Biopharma, Dicerna, Kaleido, Gilead, Roche, and Springbank; speaker for Abbott and Gilead Linda M. Fredrick: Employee of AbbVie and may own stock or share options Wenjing Lu: Employee of AbbVie and may own stock or share options Wei Liu: Employee of AbbVie and may own stock or share options Hari V. Kalluri: Employee of AbbVie and may own stock or share options Preethi Krishnan: Employee of AbbVie and may own stock or share options Rakesh Tripathi: Employee of AbbVie and may own stock or share options Niloufar Mobashery: Former employee of AbbVie and owns stocks Margaret Burroughs: Employee of AbbVie and may own stock or share options Armen Asatryan: Former employee of AbbVie and may own stock or share options; currently with AveXis, a Novartis company Jidong Jia: Nothing to disclose Jinlin Hou: Consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Johnson & Johnson and Roche; grants from Bristol-Myers Squibb and Johnson & Johnson. Ethics Approval Statement: The study protocols and amendments were approved by an independent ethics committee/institutional review board for each study site.