SIMEPREVIR (TMC435) WITH PEGINTERFERON/RIBAVIRIN FOR TREATMENT OF CHRONIC HCV GENOTYPE-1 INFECTION IN TREATMENT-NAIVE PATIENTS: RESULTS FROM QUEST-2, A PHASE III TRIAL
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Data de publicação
2013
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Editora
ELSEVIER SCIENCE BV
Autores
MANNS, M.
MARCELLIN, P.
POORDAD, F. P. Fred
BUTI, M.
HORSMANS, Y.
JANCZEWSKA, E. J. Ewa
VILLAMIL, F.
PEETERS, M.
LENZ, O.
Citação
JOURNAL OF HEPATOLOGY, v.58, suppl.1, p.S568-S568, 2013
Resumo
Background and Aims: Simeprevir is a potent, once-daily, oral, investigational HCV NS3/4A protease inhibitor. QUEST-2 (NCT01290679) is a Phase III, randomised, double-blind, placebo-controlled trial assessing the efficacy, safety and tolerability of simeprevir versus placebo as part of a regimen including peginterferon a-2α (pegIFNα-2a) or pegIFNα-2b/ribavirin (PR) in treatment-naïve patients chronically infected with genotype-1 HCV.Safety and SVR12 results from a primary (Week 60) analysis are presented. Methods: Patients (n=391), randomised 2:1 and stratified by HCV genotype-1 subtype and host IL28B genotype, received simeprevir (150mg QD)+PR or placebo+PR for 12 weeks, followed by PR alone. Total treatment duration was 24 or 48 weeks (simeprevir group) based on response-guided therapy (RGT) criteria (HCVRNA < 25IU/mL Week 4 and undetectable Week 12) or 48 weeks (placebo group). Table 1 Percentage of patients achieving SVR12 Placebo/PR Simeprevir/PR All patients 50% 81% Treated with pegIFNα-2a/pegIFNα-2b 62%/42% 88%/78% Patients who met RGT criteria not applicable 86% IL28B genotype CC/CT/TT 81%/41%/19% 96%/80%/58% HCV subtype 1a or other/1b 46%/53% 80%/82% METAVIR score F0–F2/F3–F4 51%/47% 85%/66% Results: Simeprevir/PR was superior to placebo/PR; SVR12: 81 vs 50%, respectively (p < 0.001). The majority (91%) of simeprevir-treated patients met RGT criteria and completed treatment at Week 24. Overall, 79% of simeprevir and 13% of placebo-treated patients achieved RVR. Treatment with simeprevir/PR led to lower rates of on-treatment failure and relapse compared to placebo/PR (7 vs 32% and 13 vs 24%, respectively). The incidence of AEs was similar between groups, regardless of the pegIFN used. The most common AEs were fatigue, influenza-like illness, pruritus and headache. A slightly higher proportion of simeprevir patients experienced rash and photosensitivity, compared to placebo (27 vs 20% and 4 vs 1%, respectively). There was no difference in the proportion of patients experiencing anaemia. Conclusions: Simeprevir 150mg QD was well tolerated, leading to a high SVR12 rate of 81% when administered with either pegIFNα-2a or pegIFNα-2b. The majority of patients (91%) receiving simeprevir was able to shorten therapy to 24 weeks.