SILEN-C3, a phase 2 randomized trial with faldaprevir plus pegylated interferon α-2a and ribavirin in treatment-naive hepatitis C virus genotype 1-infected patients.
Faldaprevir is an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor which, when administered for 24 weeks in combination with pegylated interferon α-2a and ribavirin (PegIFN/RBV) in treatment-naive patients in a prior study (SILEN-C1; M. S. Sulkowski et al., Hepatology 57:2143-2154, 2013, doi:10.1002/hep.26276), achieved sustained virologic response (SVR) rates of 72 to 84%. The current randomized, open-label, parallel-group study compared the efficacy and safety of 12 versus 24 weeks of 120 mg faldaprevir administered once daily, combined with 24 or 48 weeks of PegIFN/RBV, in 160 treatment-naive HCV genotype 1 patients. Patients with maintained rapid virologic response (HCV RNA of <25 IU/ml at week 4 and undetectable at weeks 8 and 12) stopped all treatment at week 24, otherwise they continued PegIFN/RBV to week 48. SVR was achieved by 67% and 74% of patients in the 12-week and 24-week groups, respectively. Virologic response rates were lower in the 12-week group from weeks 2 to 12, during which both groups received identical treatment. SVR rates were similar in both groups for patients achieving undetectable HCV RNA. Most adverse events were mild or moderate, and 6% of patients in each treatment group discontinued treatment due to adverse events. Once-daily faldaprevir at 120 mg for 12 or 24 weeks with PegIFN/RBV resulted in high SVR rates, and the regimen was well tolerated. Differences in the overall SVR rates between the 12-week and 24-week groups were not statistically significant and possibly were due to IL28B genotype imbalances; IL28B genotype was not tested, as its significance was not known at the time of the study. These results supported phase 3 evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT00984620).
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA douglas.dieterich@mountsinai.org.
Douglas
D
Dieterich
Service d'Hépatologie, AP-HP Hôpital Beaujon, INSERM UMR 1149, CRI, Université Paris Diderot, Clichy, France.
Tarik
T
Asselah
Department of Liver Diseases, University of Rennes 1, Rennes, France.
Dominique
D
Guyader
Sektion Hepatologie, Department für Innere Medizin, Neurologie und Dermatologie, Klinik für Gastroenterologie und Rheumatologie, Universitätsklinik Leipzig AöR, Leipzig, Germany.
Thomas
T
Berg
Klinik für Innere Medizin, Klinikum Konzstanz, Constance, Germany.
Marcus
M
Schuchmann
Center for HIV and Hepatogastroenterology, Düsseldorf, Germany.
Stefan
S
Mauss
Service d'Hépato-Gastroentérologie, Hôpital Pitié-Salpêtrière, Paris, France.
Vlad
V
Ratziu
Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
Peter
P
Ferenci
Liver Unit-IRB-INSERM1040, Hôpital Saint Eloi, Montpellier, France.
Dominique
D
Larrey
Department of Gastroenterology and Hepatology, Elisabethinen Hospital Linz, Linz, Austria.
Andreas
A
Maieron
Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA.
Jerry O
JO
Stern
Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA.
Melek
M
Ozan
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Yakov
Y
Datsenko
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Wulf Otto
WO
Böcher
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Gerhard
G
Steinmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000621:Aminoisobutyric Acids; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D011804:Quinolines; D012367:RNA, Viral / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D055815:Young Adult; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000621:Aminoisobutyric Acids; D000998:Antiviral Agents; D002352:Carrier Proteins; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011392:Proline; D011804:Quinolines; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D013844:Thiazoles; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C552340:faldaprevir; C100416:peginterferon alfa-2a