Phase 3 Placebo-Controlled Study Of Interferon-Free, 12-Week Regimen Of ABT-450/R/ABT-267, ABT-333, And Ribavirin In 631 Treatment-Naïve Adults With Hepatitis C Virus Genotype 1
J.J. Feld,1 K.V. Kowdley,2 E. Coakley,3 S. Sigal,4 D. Nelson,5 D. Crawford,6,7 O. Weiland,8 H. Aguilar,9 J. Xiong,3 B. DaSilva-Tillmann,3 L. Larsen3, T. Podsadecki,3
Background and Aims: ABT-450 is an HCV NS3/4A protease inhibitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta. ABT-267 is an NS5A inhibitor, and ABT-333 is an NS5B RNA polymerase inhibitor. Safety and efficacy results from a phase 3 trial of ABT-450/r/ABT-267 + ABT-333 with RBV (3D+RBV) in treatment-naïve HCV genotype (GT)1-infected patients are reported.
Results: During the double-blind period, 473 patients received 3D+RBV and 158 received placebos. The table shows baseline characteristics for each arm and efficacy for Arm A. The intention-to-treat SVR12 rate for Arm A was 96.2%; this rate was superior to the historical SVR rate for telaprevir and peginterferon/ribavirin. On-treatment failure and post-treatment relapse occurred in 0.2% and 1.5% of patients, respectively.
During the double-blind period, the most common treatment-emergent adverse events (AEs) in Arms A and B were fatigue (34.7% and 28.5%, respectively) and headache (33.0% and 26.0%, respectively); the frequency of these events did not differ between arms (P=NS). Discontinuation due to AEs occurred in 0.6% of patients in each arm.
Conclusions: In this study, the interferon-free, 3D+RBV regimen was generally well-tolerated and achieved a high SVR12 rate among treatment-naïve HCV GT1-infected patients.
1Toronto Western Hospital Liver Centre, Toronto, ON, Canada, 2Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, 3AbbVie Inc., North Chicago, IL, 4NYU Langone Medical Center, New York, NY, 5University of Florida College of Medicine, Gainesville, FL, United States, 6Gallipoli Medical Research Foundation, 7The University of Queensland, Brisbane, QLD, Australia, 8Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden, 9Louisiana Research Center, LLC, Shreveport, LA, United States