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DAUPHINE : a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha‐2a/ribavirin in HCV genotypes 1 or 4
Author(s) -
Everson Gregory,
Cooper Curtis,
Hézode Christophe,
Shiffman Mitchell L.,
Yoshida Eric,
BeltranJaramillo Teresita,
Andreone Pietro,
Bruno Savino,
Ferenci Peter,
Zeuzem Stefan,
Brunda Michael,
Le Pogam Sophie,
Nájera Isabel,
Zhou Julian,
Navarro Mercidita T.,
Voulgari Athina,
Shulman Nancy S.,
Yetzer Ellen S.
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12471
Subject(s) - ritonavir , medicine , ribavirin , gastroenterology , population , hepatitis c virus , viral load , virology , virus , environmental health , antiretroviral therapy
Abstract Background & Aims 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 II b 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 ( eRVR 2: HCV RNA <15 IU/ml during Weeks 2–10) stopped all therapy at Week 12; non‐ eRVR 2 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 SVR 24 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.