Faldaprevir, pegylated interferon, and ribavirin for treatment-naïve HCV genotype-1: pooled analysis of two phase 3 trials
Journal
Annals of Hepatology
Journal Volume
15
Journal Issue
3
Pages
333-349
Date Issued
2016
Author(s)
Jensen D.M.
Asselah T.
Dieterich D.
Foster G.R.
Sulkowski M.S.
Zeuzem S.
Mantry P.
Yoshida E.M.
Moreno C.
Ouzan D.
Wright M.
Morano L.E.
Buynak R.
Bourlière M.
Hassanein T.
Nishiguchi S.
Omata M.
Paik S.W.
Wong D.K.
Tam E.
Kaita K.
Victor Feinman S.
Stern J.O.
Scherer J.
Quinson A.-M.
Voss F.
Gallivan J.-P.
Böcher W.O.
Ferenci P.
Abstract
Introduction & aim. Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-na?ve patients with chronic HCV genotype-1 infection. Material and methods. Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24–48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). Results. SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17–31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16–30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious AEs were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. Conclusion. Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270. ? 2016, Fundacion Clinica Medica Sur. All rights reserved.
Subjects
Direct-acting antiviral; Hepatitis C; SVR12; Viral hepatitis
SDGs
Other Subjects
alanine aminotransferase; bilirubin; faldaprevir; peginterferon alpha2a plus ribavirin; alpha interferon; antivirus agent; biological marker; carrier protein; macrogol derivative; N-((cyclopentyloxy)carbonyl)-3-methylvalyl-4-((8-bromo-7-methoxy-2-(2-((2-methylpropanoyl)amino)-1,3-thiazol-4-yl)quinolin-4-yl)oxy)-N-(1-carboxy-2-ethenylcyclopropyl)prolinamide; NS3 protein, hepatitis C virus; NS4A cofactor peptide, Hepatitis C virus; oligopeptide; peginterferon alpha2a; proteinase inhibitor; recombinant protein; ribavirin; thiazole derivative; viral protein; virus RNA; adult; aged; alanine aminotransferase blood level; alopecia; anemia; Article; bilirubin blood level; clinical effectiveness; controlled study; coughing; decreased appetite; diarrhea; double blind procedure; drug dose comparison; drug safety; drug tolerability; drug withdrawal; dry skin; elastography; fatigue; female; fever; headache; hemoglobin blood level; hepatitis C; Hepatitis C virus genotype 1; human; insomnia; jaundice; leukocyte count; loading drug dose; lymphocyte count; major clinical study; male; morning dosage; multicenter study; myalgia; nausea; neutrophil count; outcome assessment; parallel design; phase 3 clinical trial; pruritus; randomized controlled trial; rash; side effect; thrombocyte count; treatment duration; treatment response; vomiting; antagonists and inhibitors; blood; combination drug therapy; drug effects; enzymology; genetics; genotype; Hepacivirus; hepatitis C; meta analysis; metabolism; middle aged; odds ratio; phase 3 clinical trial (topic); randomized controlled trial (topic); statistical model; time factor; treatment outcome; virus load; Adult; Antiviral Agents; Biomarkers; Carrier Proteins; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C; Humans; Interferon-alpha; Logistic Models; Male; Middle Aged; Odds Ratio; Oligopeptides; Polyethylene Glycols; Protease Inhibitors; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin; RNA, Viral; Thiazoles; Time Factors; Treatment Outcome; Viral Load; Viral Nonstructural Proteins
Publisher
Fundacion Clinica Medica Sur
Type
journal article