Abstract | BACKGROUND: METHODS: We did this randomised, double-blind, phase 3 trial at 169 investigational sites in 24 countries. We enrolled adults (≥18 years) with chronic HCV genotype 1 infection, compensated liver disease, and plasma HCV RNA higher than 10 000 IU/mL who were null or partial responders during at least one previous course of peginterferon alfa-2a and ribavirin treatment. We randomly assigned (1:1) patients (stratified by HCV genotype 1 subtype [1a plus other/1b] and previous treatment response [partial or null]) to receive simeprevir (150 mg once a day) plus telaprevir placebo (three times a day 7-9 h apart) or telaprevir (750 mg three times a day) plus simeprevir placebo (once a day) in combination with peginterferon alfa-2a and ribavirin for 12 weeks followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. The primary efficacy endpoint was sustained virological response 12 weeks after end of treatment (SVR12) in the intention-to-treat and the per-protocol population. We compared groups with the Cochran-Mantel-Haenszel test. We established a non-inferiority margin of 12%. Adverse events were reported descriptively. This trial is registered with ClinicalTrials.gov, number NCT01485991. FINDINGS: INTERPRETATION:
Simeprevir once a day with peginterferon alfa-2a and ribavirin was well tolerated in HCV genotype 1-infected previous non-responders and was non-inferior to telaprevir, thus providing an alternative treatment in areas of the world where all-oral HCV regimens are not available or accessible. FUNDING: Janssen.
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Authors | K Rajender Reddy, Stefan Zeuzem, Fabien Zoulim, Ola Weiland, Andrzej Horban, Carol Stanciu, Federico Guillermo Villamil, Pietro Andreone, Jacob George, Elisabeth Dammers, Min Fu, Darryl Kurland, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Thierry Verbinnen, Jane Scott, Wolfgang Jessner |
Journal | The Lancet. Infectious diseases
(Lancet Infect Dis)
Vol. 15
Issue 1
Pg. 27-35
(Jan 2015)
ISSN: 1474-4457 [Electronic] United States |
PMID | 25482330
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Antiviral Agents
- Heterocyclic Compounds, 3-Ring
- Interferon-alpha
- Oligopeptides
- Placebos
- Recombinant Proteins
- Sulfonamides
- Polyethylene Glycols
- Ribavirin
- telaprevir
- Simeprevir
- peginterferon alfa-2a
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Topics |
- Adolescent
- Adult
- Aged
- Antiviral Agents
(therapeutic use)
- Double-Blind Method
- Female
- Genotype
- Hepacivirus
(classification, genetics, isolation & purification)
- Hepatitis C, Chronic
(drug therapy, virology)
- Heterocyclic Compounds, 3-Ring
(therapeutic use)
- Humans
- Interferon-alpha
(therapeutic use)
- Male
- Middle Aged
- Oligopeptides
(therapeutic use)
- Placebos
(administration & dosage)
- Polyethylene Glycols
(therapeutic use)
- Recombinant Proteins
(therapeutic use)
- Ribavirin
(therapeutic use)
- Simeprevir
- Sulfonamides
(therapeutic use)
- Treatment Outcome
- Young Adult
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