TY  - JOUR
A1  - Forns, Xavier
A1  - Lawitz, Eric
A1  - Zeuzem, Stefan
A1  - Gane, Ed
A1  - Bronowicki, Jean-Pierre
A1  - Andreone, Pietro
A1  - Horban, Andrzej
A1  - Brown, Ashley
A1  - Peeters, Monika
A1  - Lenz, Oliver
A1  - Ouwerkerk–Mahadevan, Sivi
A1  - Scott, Jane
A1  - De La Rosa, Guy
A1  - Kalmeijer, Ronald
A1  - Sinha, Rekha
A1  - Beumont–Mauviel, Maria
T1  - Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial
T2  - Gastroenterology
N2  - Background & Aims: Simeprevir is an oral, once-daily inhibitor of hepatitis c virus (HCV) protease NS3/4A. We investigated the safety and efficacy of simeprevir with peg-interferon α-2a and ribavirin (PR) in a randomized, double-blind, placebo-controlled, phase 3 trial of patients with HCV genotype 1 infection who relapsed after previous interferon-based therapy.
Methods: Patients were assigned randomly (2:1) to groups given simeprevir (150 mg, once daily) and PR (n = 260) or placebo and PR (n = 133) for 12 weeks. Patients then were given PR alone for 12 or 36 weeks (simeprevir group, based on response-guided therapy criteria) or 36 weeks (placebo group).
Results: Simeprevir and PR was significantly superior to placebo and PR; rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were 79.2% vs 36.1%, respectively (43.8% difference; 95% confidence interval, 34.6–53.0; P < .001). Among patients given simeprevir, 92.7% met the response-guided therapy criteria and were eligible to complete PR at week 24; of these, 83.0% achieved SVR12. HCV RNA was undetectable at week 4 in 77.2% of patients given simeprevir and 3.1% given placebo. On-treatment failure and relapse rates were lower among patients given simeprevir and PR than those given placebo and PR (3.1% vs 27.1%, and 18.5% vs 48.4%, respectively). Patients given simeprevir did not have adverse events beyond those that occurred in patients given PR alone. Most adverse events were grades 1/2; the prevalence of anemia and rash was similar in both groups. Patients in both groups reported similar severity of fatigue and functional impairments during the study, but duration was reduced among patients given simeprevir.
Conclusions: In a phase 3 trial of patients who had relapsed after interferon-based therapy, the addition of simeprevir to PR was generally well tolerated, with an SVR12 rate of 79.2%. Most patients (92.7%) receiving simeprevir were able to shorten therapy to 24 weeks. ClinicalTrials.gov number: NCT01281839.
KW  - PROMISE
KW  - Chronic Hepatitis C
KW  - Drug
KW  - DAA
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/40340
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-403409
SN  - 0016-5085
N1  - Open access under CC BY-NC-ND license.
VL  - 146
IS  - 7
SP  - 1669
EP  - 1679
PB  - American Gastroenterological Association
CY  - Philadelphia, Pa.
ER  -