TY  - JOUR
A1  - Asselah, Tarik
A1  - Moreno, Christophe
A1  - Sarrazin, Christoph
A1  - Gschwantler, Michael
A1  - Foster, Graham R.
A1  - Craxı, Antonio
A1  - Buggisch, Peter
A1  - Ryan, Robert
A1  - Lenz, Oliver
A1  - Scott, Jane
A1  - Dooren, Gino van
A1  - Lonjon-Domanec, Isabelle
A1  - Schlag, Michael
A1  - Buti, Maria
T1  - An open-label trial of 12-week Simeprevir plus Peginterferon/Ribavirin (PR) in treatment-naïve patients with hepatitis C Virus (HCV) genotype 1 (GT1)
T2  - PLoS one
N2  - Background: Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.
Methods: In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0–F2 fibrosis, patients with HCV-RNA <25 IU/mL (detectable/undetectable) at Week 2, and undetectable HCV-RNA at Weeks 4 and 8, stopped all treatment at Week 12. All other patients continued PR for a further 12 weeks. Baseline factors significantly associated with SVR12 were identified through logistic regression.
Results: Of 163 patients who participated in the study, 123 (75%) qualified for 12-week treatment; of these, 81 (66%) achieved SVR12. Baseline factors positively associated with SVR12 rates in patients receiving the 12-week regimen were: IL28B CC genotype: (94% SVR12); HCV RNA ≤800,000 IU/mL (82%); F0–F1 fibrosis (74%). Among all 163 patients, 94% experienced ≥1 adverse event (AE), 4% a serious AE, and 2.5% discontinued due to an AE. Reduced impairment in patient-reported outcomes was observed in the 12-week vs >12-week regimen.
Conclusions: Overall SVR12 rate (66%) was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.
Trial Registration: ClinicalTrials.gov NCT01846832
KW  - Fibrosis
KW  - Hepatitis C virus
KW  - Drug therapy
KW  - Decision trees
KW  - Regression analysis
KW  - Adverse events
KW  - Multivariate analysis
KW  - Viral load
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45756
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-457565
SN  - 1932-6203
N1  - Copyright: © 2016 Asselah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 11
IS  - (7): e0158526
SP  - 1
EP  - 15
PB  - PLoS
CY  - Lawrence, Kan.
ER  -