title: 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01830127.
authors.affiliation: J.W. Goethe-University Hospital, Frankfurt am Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Hannover Medical School, Hannover, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.affiliation: Hospital Universitario Puerta de Hierro, Universidad Autonomy de Madrid. CIBERehd, Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Calleja
authors.affiliation: Hospital Universitario La Paz/Carlos III, CIBERehd, IdiPAZ, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Garcia-Samaniego
authors.affiliation: Hospital Clínic, CIBERehd, IDIBAPS, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, United States of America.
authors.forename: Renee
authors.initials: R
authors.lastname: Kaste
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, United States of America.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Bai
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, United States of America.
authors.forename: Jerry O
authors.initials: JO
authors.lastname: Stern
mesh_terms: D000179:Acrylates / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use*; D011379:Prognosis; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D012367:RNA, Viral / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D000179:Acrylates; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D001562:Benzimidazoles; D009842:Oligopeptides; D011804:Quinolines; D012367:RNA, Viral; D013844:Thiazoles; D012254:Ribavirin; C000592437:deleobuvir; C552340:faldaprevir; D011392:Proline; D007930:Leucine