Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II): alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II)
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| Title: | Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II): alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II) |
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| Authors: | Zeuzem, S, Flisiak, R, Vierling, J. M, Mazur, W, Mazzella, G, Thongsawat, S, Abdurakhmanov, D, Van Kính, N, Calistru, P, Heo, J, Stanciu, C, Gould, M, Makara, M, Hsu, S. J, Buggisch, P, Samuel, D, Mutimer, D, Nault, B, Merz, M, Bao, W, Griffel, L. H, Brass, C, Naoumov, N. V, ALBERTI, ALFREDO, ESSENTIAL II Study Group |
| Contributors: | Basic (bio-) Medical Sciences, Liver Cell Biology, FORMER_Laboratory of Molecullar and Cellular Therapy |
| Source: | Alimentary Pharmacology & Therapeutics. 42:829-844 |
| Publisher Information: | Wiley, 2015. |
| Publication Year: | 2015 |
| Subject Terms: | Adult, Male, 0301 basic medicine, Double-blind method, Adolescent, Genotype, chronic - drug therapy, Antiviral agents - administration & dosage, Antiviral agents - adverse effects, Recombinant proteins - adverse effects, Hepacivirus, Antiviral Agents, Polyethylene Glycols, Cyclosporine - adverse effects, 03 medical and health sciences, Double-Blind Method, Interferon-alpha - adverse effects, Ribavirin, Humans, Pharmacology (medical), Treatment outcome, Middle aged, Aged, combination, Interferon-alpha - administration & dosage, Ribavirin - administration & dosage, chronic - virology, Polyethylene glycols - adverse effects, Cyclosporine, Drug Therapy, Combination, Female, Hepatitis C, Chronic, Interferon-alpha, Middle Aged, Recombinant Proteins, Treatment Outcome, United States, Young Adult, Hepatitis C, Hepacivirus - genetics, 3. Good health, Cyclosporine - administration & dosage, Young adult, Recombinant proteins - administration & dosage, Drug therapy, Hepacivirus - drug effects, Polyethylene glycols - administration & dosage, Ribavirin - adverse effects |
| Description: | SummaryBackgroundAlisporivir (ALV) is an oral, host‐targeting agent with pangenotypic anti‐hepatitis C virus (HCV) activity and a high barrier to resistance.AimTo evaluate efficacy and safety of ALV plus peginterferon‐α2a and ribavirin (PR) in treatment‐naïve patients with chronic HCV genotype 1 infection.MethodsDouble‐blind, randomised, placebo‐controlled, Phase 3 study evaluating ALV 600 mg once daily [response‐guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.ResultsA total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose‐dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.ConclusionsAlisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment‐naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon‐free combination regimens. |
| Document Type: | Article |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 1365-2036 0269-2813 |
| DOI: | 10.1111/apt.13342 |
| Access URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.13342 https://pubmed.ncbi.nlm.nih.gov/26238707 https://www.ncbi.nlm.nih.gov/pubmed/26238707 https://iris.unipa.it/handle/10447/401609 https://research.birmingham.ac.uk/portal/en/publications/randomised-clinical-trial(e474dae5-6b05-447d-87e4-f5433e0ceb72).html https://researchportal.vub.be/en/publications/randomised-clinical-trial-alisporivir-combined-with-peginterferon https://onlinelibrary.wiley.com/doi/10.1111/apt.13342 https://europepmc.org/abstract/MED/26238707 https://hdl.handle.net/11577/3196002 https://doi.org/10.1111/apt.13342 https://hdl.handle.net/10447/401609 https://doi.org/10.1111/apt.13342 http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-2036 https://biblio.vub.ac.be/vubir/(361ab324-7923-48b1-98e4-af989bb0a437).html http://hdl.handle.net/10722/227364 |
| Rights: | Wiley Online Library User Agreement |
| Accession Number: | edsair.doi.dedup.....0fc3d921ba63b7637deecda5f6b70323 |
| Database: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | SummaryBackgroundAlisporivir (ALV) is an oral, host‐targeting agent with pangenotypic anti‐hepatitis C virus (HCV) activity and a high barrier to resistance.AimTo evaluate efficacy and safety of ALV plus peginterferon‐α2a and ribavirin (PR) in treatment‐naïve patients with chronic HCV genotype 1 infection.MethodsDouble‐blind, randomised, placebo‐controlled, Phase 3 study evaluating ALV 600 mg once daily [response‐guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that time, 87% of patients had received ≥12 weeks and 20% had received ≥24 weeks of ALV/PR triple therapy.ResultsA total of 1081 patients were randomised (12% cirrhosis, 55% CT/TT IL28B). Addition of ALV to PR improved virological response in a dose‐dependent fashion. Overall, sustained virological response (SVR12; primary endpoint) was 69% in all ALV groups vs. 53% in PR control. Highest SVR12 (90%) was achieved in patients treated with ALV 400 mg twice daily and PR for >24 weeks. Seven cases of pancreatitis were reported, with similar frequency between ALV/PR and PR control groups (0.6% vs. 0.8% respectively). Adverse events seen more frequently with ALV/PR than with PR alone were anaemia, thrombocytopenia, hyperbilirubinaemia and hypertension.ConclusionsAlisporivir, especially the 400 mg twice daily regimen, increased efficacy of PR therapy in treatment‐naïve patients with HCV genotype 1 infection. The mechanism of action and pangenotypic activity suggest that alisporivir could be useful in interferon‐free combination regimens. |
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| ISSN: | 13652036 02692813 |
| DOI: | 10.1111/apt.13342 |