Randomized trial of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 or 4 chronic hepatitis C.
J Hepatol
; 61(6): 1220-7, 2014 Dec.
Article
in En
| MEDLINE
| ID: mdl-25038486
ABSTRACT
BACKGROUND & AIMS:
Asunaprevir is a selective HCV NS3 protease inhibitor, active against genotypes 1, 4, 5, and 6 in vitro. We evaluated asunaprevir plus peginterferon alfa-2a/ribavirin (PegIFNα/RBV) for genotype 1 and 4 chronic HCV.METHODS:
In this phase 2b, double-blind, placebo-controlled study, treatment-naive adults with genotype 1 (n=213) or 4 (n=25) were randomly assigned (31) to asunaprevir 200mg or placebo twice daily plus PegIFNα/RBV. Asunaprevir recipients, achieving protocol-defined response (HCV-RNA below quantification limit at week 4 and undetectable at week 10), were rerandomized at week 12 to continue asunaprevir-based triple therapy or receive placebo plus PegIFNα/RBV for weeks 13-24. Patients without protocol-defined response (PDR) and placebo recipients continued PegIFNα/RBV through week 48. Co-primary end points were undetectable HCV-RNA at week 4 and 12 (eRVR) and 24 weeks posttreatment (SVR24).RESULTS:
Most patients were male (64.3%), white (83.6%), and had non-CC IL28B genotypes (71.3%). Among genotype 1 patients, eRVR rates (asunaprevir vs. placebo) were 67% (80% CI 62, 72) vs. 6% (80% CI 2, 10); corresponding SVR24 rates were 64% (80% CI 59, 68) vs. 44% (80% CI 36, 53). SVR24 among genotype 4 patients was 89% (asunaprevir) vs. 43% (placebo). Rates of rash and haematologic adverse events were similar between treatment groups. Five asunaprevir-treated patients had grade 4 alanine aminotransferase elevations that resolved following discontinuation (n=4) or with continued dosing (n=1).CONCLUSIONS:
Addition of asunaprevir to PegIFNα/RBV in treatment-naive genotype 1- or 4-infected patients improves response rates and is well tolerated, with aminotransferase elevations that were manageable with appropriate monitoring. ClinicalTrials.gov ID NCT01030432.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Polyethylene Glycols
/
Ribavirin
/
Sulfonamides
/
Interferon-alpha
/
Hepatitis C, Chronic
/
Isoquinolines
Type of study:
Clinical_trials
/
Guideline
Limits:
Adolescent
/
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2014
Type:
Article