title: DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha-2a/ribavirin in HCV genotypes 1 or 4.
abstract: OBJECTIVE
  Danoprevir is a hepatitis C virus (HCV) protease inhibitor with activity against genotypes (G)1/G4, which is maintained at lower doses by ritonavir-boosting. We report results of a large, randomized, active-controlled phase IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection.
  
  
  METHODS
  Treatment-naive patients with HCV G1/4 infection were randomized to twice-daily danoprevir/r 200/100 mg (A, n = 92); 100/100 mg (B, n = 93); or 50/100 mg (C, n = 94) plus P/R for 24 weeks; twice-daily danoprevir/r 100/100 mg (D, n = 94) plus P/R for 12 or 24 weeks; or P/R alone (E, n = 44) for 48 weeks. Patients in the response-guided therapy arm (D) with an extended rapid virological response (eRVR2: HCV RNA <15 IU/ml during Weeks 2-10) stopped all therapy at Week 12; non-eRVR2 patients continued all treatment to Week 24. The primary efficacy endpoint was sustained the virological response (SVR24: HCV RNA <15 IU/ml after 24 weeks of untreated follow-up).
  
  
  RESULTS
  SVR24 rates in Arms A, B, C, D and E were 89.1%, 78.5%, 66.0%, 69.1% and 36.4%, respectively, in the overall population; 83.6%, 69.6%, 60.3%, 59.2% and 38.5% in G1a-infected patients, 96.6%, 93.1%, 73.1%, 78.4% and 28.6% in G1b-infected patients and 100%, 87.5%, 100%, 100% and 66.7% in G4-infected patients. Danoprevir/r plus P/R was generally well tolerated compared with P/R alone. There was a higher incidence of serious adverse events in danoprevir-treatment arms, but most were associated with P/R.
  
  
  CONCLUSIONS
  The combination of danoprevir/r plus P/R is efficacious in treatment-naïve patients with HCV genotype 1 or 4 infection.
authors: School of Medicine, University of Colorado, Denver, CO, USA.
authors: Gregory
authors: G
authors: Everson
authors: Curtis
authors: C
authors: Cooper
authors: Christophe
authors: C
authors: Hézode
authors: Mitchell L
authors: ML
authors: Shiffman
authors: Eric
authors: E
authors: Yoshida
authors: Teresita
authors: T
authors: Beltran-Jaramillo
authors: Pietro
authors: P
authors: Andreone
authors: Savino
authors: S
authors: Bruno
authors: Peter
authors: P
authors: Ferenci
authors: Stefan
authors: S
authors: Zeuzem
authors: Michael
authors: M
authors: Brunda
authors: Sophie
authors: S
authors: Le Pogam
authors: Isabel
authors: I
authors: Nájera
authors: Julian
authors: J
authors: Zhou
authors: Mercidita T
authors: MT
authors: Navarro
authors: Athina
authors: A
authors: Voulgari
authors: Nancy S
authors: NS
authors: Shulman
authors: Ellen S
authors: ES
authors: Yetzer
mesh_terms: D000328:Adult; D003521:Cyclopropanes; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D054833:Isoindoles; D007769:Lactams / Q000627:therapeutic use*; D047029:Lactams, Macrocyclic; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D003521:Cyclopropanes; D016898:Interferon-alpha; D054833:Isoindoles; D007769:Lactams; D047029:Lactams, Macrocyclic; D012367:RNA, Viral; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; C553752:danoprevir; D011392:Proline; D019438:Ritonavir; C100416:peginterferon alfa-2a
keywords: danoprevir; hepatitis C virus; response-guided therapy; ritonavir-boosting; sustained virological response