An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

Abstract

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.

Conflict of interest statement

Competing Interests: T. Asselah has served as a consultant/speaker for AbbVie, Achillion, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck, and Roche. C. Moreno has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals and Promethera. He has received research grants from Astellas, Gilead Sciences, Janssen Pharmaceuticals, Novartis and Roche. C. Sarrazin has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme, and Qiagen. He has received research grants from Abbott, Gilead Sciences, Janssen Pharmaceuticals, Roche, Qiagen. M. Gschwantler has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Merck Sharpe & Dohme and Roche. G. R. Foster has been a paid speaker or adviser for Abbvie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Merck Sharpe & Dohme and Roche. He has received research grants from Gilead Sciences and Springbank. A. Craxí has no conflicts of interest. P. Buggisch has been a paid speaker or adviser for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe and Dohme and Roche. He has received research grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharpe & Dohme and Roche. M. Buti has been a paid speaker or adviser for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme, and Novartis. She has been a lecturer for Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme, and Novartis. She has been a clinical investigator for Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme, Novartis, and Roche. R. Ryan, O. Lenz, J. Scott, G. van Dooren, I. Lonjon-Domanec, M. Schlag are employees of Janssen Pharmaceuticals. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Patient disposition flow chart.

Fig 2. SVR4 and SVR12 rates for all patients, patients receiving 12 weeks of treatment, and patients receiving >12 weeks of treatment.

Fig 3

Percentage of [A] all patients, and [B] patients receiving 12 weeks of treatment who achieved SVR12, according to baseline characteristics and on-treatment factors.

Fig 4

Forest plot showing the results of the final multivariate logistic regression analyses of factors associated with [A] SVR12 and [B] viral relapse in patients receiving 12 weeks of treatment.