ClinicalTrials.gov number: NCT01220947
DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha-2a/ribavirin in HCV genotypes 1 or 4
Article first published online: 12 FEB 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
How to Cite
Everson, G., Cooper, C., Hézode, C., Shiffman, M. L., Yoshida, E., Beltran-Jaramillo, T., Andreone, P., Bruno, S., Ferenci, P., Zeuzem, S., Brunda, M., Le Pogam, S., Nájera, I., Zhou, J., Navarro, M. T., Voulgari, A., Shulman, N. S. and Yetzer, E. S. (2014), DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha-2a/ribavirin in HCV genotypes 1 or 4. Liver International. doi: 10.1111/liv.12471
- Article first published online: 12 FEB 2014
- Accepted manuscript online: 19 JAN 2014 05:33AM EST
- Manuscript Accepted: 11 JAN 2014
- Manuscript Received: 25 OCT 2013
- F. Hoffmann-La Roche Ltd.
- hepatitis C virus;
- response-guided therapy;
- sustained virological response
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 IIb study of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a/ribavirin (P/R) in treatment-naive patients with HCV G1/4 infection.
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).
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.
The combination of danoprevir/r plus P/R is efficacious in treatment-naïve patients with HCV genotype 1 or 4 infection.