HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment

Abstract

This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and 'other' (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%-83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%-76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53-61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis.

Trial registration: ClinicalTrials.gov NCT01830127.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: Christoph Sarrazin has served on advisory boards for Abbott, AbbVie, Achillion, BI, BMS, Janssen, Gilead, Merck/MSD, Novartis, Roche, Vertex; speaker bureaus for Abbott, AbbVie, BI, BMS, Falk, Gilead, Janssen, Merck/MSD, Novartis, Roche, and Siemens; and received research support from Abbott, Gilead, Janssen, Merck/MSD, Roche, and Siemens. Michael Manns has received speaker fees from AbbVie, BMS, Gilead, GSK, Janssen, Merck, and Roche; has worked as a consultant for AbbVie, Achillion, BMS, Boehringer Ingelheim, Gilead, GSK, Idenix, Janssen, Merck, Novartis, Roche, and Vertex; and has received grant/research support from AbbVie, BMS, Boehringer Ingelheim, Gilead, Janssen, Merck, Novartis, and Roche. Jose Luis Calleja has served as an advisory board member for Gilead, Janssen, Merck Sharp & Dohme and Boehringer Ingelheim; has served as a speaker for Gilead, Janssen, Merck Sharp & Dohme and Roche. Javier Garcia-Samaniego has worked as a consultant for BMS, Boehringer Ingelheim, Gilead, Janssen, MSD, and Roche; as a speaker for Gilead, Janssen, and Roche; and has received research funds from Gilead and Roche. Xavier Forns has received consulting or advisory fees from Janssen, Gilead, and Abbvie. Renee Kaste, Xiaofei Bai, Jing Wu and Jerry O. Stern are employees of Boehringer Ingelheim Pharmaceuticals, Inc. This study was wholly funded and supported by Boehringer Ingelheim Pharma GmbH & Co. KG. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Patient disposition.

AE, adverse event; CPA, Child-Pugh A group; CPB, Child-Pugh B group.