title: Simeprevir plus peginterferon/ribavirin for HCV genotype 1-infected treatment-naïve patients in China and South Korea.
abstract: OBJECTIVE
  Approximately one-third of patients with hepatitis C virus (HCV) genotype (GT) 1 infection live in East Asia. This study evaluated the efficacy, pharmacokinetics, safety, and tolerability of simeprevir plus peginterferon alpha-2a and ribavirin (PR) in HCV GT1-infected, treatment-naïve, Asian patients with compensated liver disease.
  
  
  METHODS
  This phase III, randomized study (NCT01725529) was conducted in China and South Korea. Patients received simeprevir 150 mg once daily (QD), simeprevir 100 mg QD, or placebo, in combination with PR for 12 weeks. Patients in the simeprevir groups received PR alone for a further 12 or 36 weeks based on response-guided treatment criteria. Patients in the placebo group received a further 36 weeks of PR alone. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Secondary endpoints were safety, pharmacokinetics, tolerability, and patient-reported outcomes.
  
  
  RESULTS
  Overall, 457 patients were treated; the majority had GT1b infection (452/457 [99%]) and IL28B CC GT (364/457 [80%]). Of the 454 patients who had liver biopsy, 26 had cirrhosis (6%). SVR12 rates were superior for both the simeprevir 100 mg (89%; P = 0.003) and 150 mg (91%; P < 0.001) groups versus placebo (76%). Adverse events were mainly grade 1/2 and occurred at a similar incidence across all treatment groups. Overall, eight patients (2%) discontinued simeprevir or placebo treatment because of adverse events.
  
  
  CONCLUSIONS
  Both simeprevir (100 mg and 150 mg QD) plus PR achieved superiority in SVR12 versus placebo plus PR in treatment-naïve, HCV GT1-infected, Asian patients and were well tolerated.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute and Peking Key Laboratory for Hepatitis C and Immune Therapy, Beijing, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Tianjin Third Central Hospital, Tianjin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Pusan National University and Medical Research Institute, Busan, Republic of Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
authors.affiliation: Henan Provincial People's Hospital, Zhengzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shang
authors.affiliation: Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Beijing You An Hospital, Capital Medical University, Beijing, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.affiliation: Gachon University Gil Medical Center, Incheon, Republic of Korea.
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Janssen Global Services LLC, Titusville, NJ, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Kalmeijer
authors.affiliation: Janssen Research & Development BVBA, Beerse, Belgium.
authors.forename: Sivi
authors.initials: S
authors.lastname: Ouwerkerk-Mahadevan
authors.affiliation: Janssen Research & Development BVBA, Beerse, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Hoeben
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Global Services LLC, Titusville, NJ, USA.
authors.forename: Thierry
authors.initials: T
authors.lastname: Verbinnen
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Rekha
authors.initials: R
authors.lastname: Sinha
authors.affiliation: China R&D and Scientific Affairs, Xi'an Janssen Pharmaceutical Company, Beijing, China.
authors.forename: MengChun
authors.initials: M
authors.lastname: Li
authors.affiliation: Janssen Global Services LLC, High Wycombe, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Scott
authors.affiliation: Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Monika
authors.initials: M
authors.lastname: Peeters
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Witek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D002681:China; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D000071066:Patient Reported Outcome Measures; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D056910:Republic of Korea; D012254:Ribavirin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000069616:Simeprevir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D055815:Young Adult; D000095022:Interferon Lambda; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; 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; C100416:peginterferon alfa-2a
keywords: East Asia; HCV non-structural (NS)3/4A protease inhibitor; hepatitis C virus; simeprevir; sustained virologic response