Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment‐naïve patients with chronic HCV genotype 1 infection (ESSENTIAL II). Issue 7 (4th August 2015)

• Record Type: Journal Article
• 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.
• Other Names: Tanno Hugo investigator.; Bessone Fernando investigator.; Terg Ruben investigator.; Frider Bernardo investigator.; Bertuzzi Romina investigator.; Desmond Paul investigator.; Zekry Amany investigator.; Weltman Martin investigator.; George Jacob investigator.; Crawford Darrell investigator.; Matthews Gail investigator.; Moreno Christophe investigator.; Van Vlierberghe Hans investigator.; Reynaert Hendrik investigator.; Gould Michael investigator.; Lee Samuel investigator.; Ramji Alnoor investigator.; Tam Edward investigator.; Marotta Paul investigator.; Yoshida Eric investigator.; Wong Florence investigator.; Feld Jordan investigator.; Samuel Didier investigator.; Marcellin Patrick investigator.; Alric Laurent investigator.; Zarski Jean‐Pierre investigator.; Zoulim Fabien investigator.; Buggisch Peter investigator.; Hinrichsen Holger investigator.; Goeser Tobias investigator.; Zeuzem Stefan investigator.; Galle Peter investigator.; Berg Thomas investigator.; Schott Eckart investigator.; Rasenack Jens investigator.; Gerken Guido investigator.; Wedemeyer Hans investigator.; Tsang Owen investigator.; Yuen Man‐Fung investigator.; Chan Henry investigator.; Hui Aric Josun investigator.; Makara Mihaly investigator.; Tornai Istvan investigator.; Gervain Judit investigator.; Szalay Ferenc investigator.; Varga Marta investigator.; Horvath Gabor investigator.; Hunyady Bela investigator.; Vincze Aron investigator.; Mazzella Giuseppe investigator.; Gaeta Giovanni Battista investigator.; Alberti Alfredo investigator.; Colombo Massimo investigator.; Andreone Pietro investigator.; Rizzetto Mario investigator.; Angelico Mario investigator.; Craxi Antonio investigator.; Picciotto Antonino investigator.; Sacchi Paolo investigator.; Vinci Maria investigator.; Invernizzi Pietro investigator.; Bruno Savino investigator.; Heo Jeong investigator.; Lee Younjae investigator.; Cho Mong investigator.; Han Sangyoung investigator.; Lee Jinwoo investigator.; Ahn Sanghoon investigator.; Lim Youngsuk investigator.; Hwang Seonggyu investigator.; Sanchez Juan investigator.; Muñoz Linda investigator.; Maldonado Hector investigator.; Mazur Wlodzimierz investigator.; Flisiak Robert investigator.; Jablkowski Maciej investigator.; Kryczka Wieslaw investigator.; Halota Waldemar investigator.; Calistru Petre investigator.; Prelipcean Cristina investigator.; Musa Manuela investigator.; Stanciu Carol investigator.; Manuc Mircea investigator.; Tanasescu Coman investigator.; Dumitrascu Dan investigator.; Abdurakhmanov Djamal investigator.; Chulanov Vladimir investigator.; Nikitin Igor investigator.; Zhdanov Konstantin investigator.; Esaulenko Elena investigator.; Maevskaya Marina investigator.; Znoyko Olga investigator.; Lamoglia Ricard Sola investigator.; Ferret Maria Buti investigator.; Garcia‐Samaniego Javier investigator.; Gomez Manuel Romero investigator.; Diago Moises investigator.; Calleja Jose Luis investigator.; Hsu Shih‐Jer investigator.; Chuang Wan‐Long investigator.; Hu Tsung‐Hui investigator.; Peng Cheng‐Yuan investigator.; Chen Chi‐Yi investigator.; Kao Jia‐Horng investigator.; Thongsawat Satawat investigator.; Sukeepaisarnjaroen Wattana investigator.; Piratvisuth Teerha investigator.; Tanwandee Tawesak investigator.; Komolmit Piyawat investigator.; Agarwal Kosh investigator.; Mutimer David investigator.; Brown Ashley investigator.; Foster Graham investigator.; McPherson Stuart investigator.; Ryder Stephen investigator.; Poulos John investigator.; Rustgi Vinod investigator.; Lyche Kip investigator.; Omarro Steven investigator.; Vierling John investigator.; Ghalib Reem investigator.; Karnam Umaprasanna investigator.; Peine Craig investigator.; Galati Joseph investigator.; Person John investigator.; De La Torre Andrew investigator.; Ravendhran Natarajan investigator.; Mushahwar Andria investigator.; O'Leary Jacqueline investigator.; Lee William investigator.; Lawitz Eric investigator.; Ankoma‐Sey Victor investigator.; King John investigator.; Pound David investigator.; Scarsella Anthony investigator.; Thuluvath Paul investigator.; Pockros Paul investigator.; Mailliard Mark investigator.; Shiffman Mitchell investigator.; Sylvestre Diana investigator.; Heiman David investigator.; Jacobson Ira investigator.; Bacon Bruce investigator.; Dimitroff James investigator.; Reindollar Robert investigator.; Tobias Hillel investigator.; Godofsky Eliot investigator.; Rodriguez‐Torres Maribel investigator.; Bennett Michael investigator.; Ben‐Zvi Jeffrey investigator.; Van Kinh Nguyen investigator.; Dao Long investigator.; Huu Hoang Bui investigator.; Minh Yen Lam investigator.; Le Thanh Ly investigator.; Van Long Dao investigator.;
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 42:Issue 7(2015)
• Page Start: 829
• Page End: 844
• Publication Date: 2015-08-04
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.13342
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Alisporivir (ALV) is an oral, host‐targeting agent with pangenotypic anti‐hepatitis C virus (HCV) activity and a high barrier to resistance. Aim: To evaluate efficacy and safety of ALV plus peginterferon‐α2a and ribavirin (PR) in treatment‐naïve patients with chronic HCV genotype 1 infection. Methods: Double‐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. Results: A 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. Conclusions: Alisporivir, 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.