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Jensen D1, Sherman KE2, Hézode C3, Pol S4, Zeuzem S5, Ledinghen V6, Tran A7, Elkhashab M8, Younes ZH9, Kugelmas M10, Mauss S11, Everson G12, Luketic V13, Vierling J14, Serfaty L15, Brunetto M16, Heo J17, Bernstein D18, McPhee F19, Hennicken D20, Mendez P21, Hughes E21, Noviello S21; on behalf of the HALLMARK-QUAD Study Team. J Hepatol. 2015 Feb 19. pii: S0168-8278(15)00125-7. doi: 10.1016/j.jhep.2015.02.018. [Epub ahead of print] |
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Author information
Abstract
BACKGROUND AND AIMS:
Improved therapies for peginterferon/ribavirin null or partial responders are needed. This study evaluated daclatasvir (NS5A inhibitor) and asunaprevir (NS3 protease inhibitor) plus peginterferon-alfa-2a and ribavirin in this patient population.
METHODS:
This open-label, phase 3 study (HALLMARK-QUAD; NCT01573351) treated patients with chronic hepatitis C virus (HCV) genotype 1 (n=354) or 4 (n=44) infection who had a prior null or partial response to peginterferon/ribavirin. Patients received daclatasvir 60 mg once-daily plus asunaprevir 100 mg twice-daily with weekly peginterferon-alfa-2a and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12) among genotype 1-infected patients.
RESULTS:
Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated SVR12 rates of 93% (95% CI 90-96) in prior non-responders infected with HCV genotype 1. SVR12 rates among genotype 4-infected patients were 98% (95% CI 93-100); one patient had a missing post-treatment week 12 HCV-RNA measurement, but achieved an SVR at post-treatment week 24, yielding a 100% SVR rate in genotype 4 patients. Prior peginterferon/ribavirin response, sex, age, IL28B genotype, or cirrhosis status did not influence SVR12 rates. Serious adverse events occurred in 6% of patients; 5% discontinued treatment due to an adverse event. Grade 3/4 laboratory abnormalities included neutropenia (22%), lymphopenia (16%), anemia (6%), thrombocytopenia (4%), and ALT/AST elevations (3% each).
CONCLUSIONS:
Daclatasvir plus asunaprevir and peginterferon/ribavirin demonstrated high rates of SVR12 in genotype 1- or 4-infected prior null or partial responders. The combination was well tolerated and no additional safety and tolerability concerns were observed compared with peginterferon/ribavirin regimens.
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