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The cyclophilin inhibitor Debio 025 combined with PEG IFNα2a significantly reduces viral load in treatment‐naïve hepatitis C patients
Author(s) -
Flisiak Robert,
Feinman Saya V.,
Jablkowski Maciej,
Horban Andrzej,
Kryczka Wieslaw,
Pawlowska Małgorzata,
Heathcote Jenny E.,
Mazzella Giuseppe,
Vandelli Carmen,
NicolasMétral Valérie,
Grosgurin Pierre,
Liz Jorge S.,
Scalfaro Pietro,
Porchet Hervé,
Crabbé Raf
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22835
Subject(s) - medicine , hepatology , placebo , gastroenterology , hepatitis c virus , adverse effect , neutropenia , pegylated interferon , immunology , chemotherapy , virus , ribavirin , pathology , alternative medicine
The anti–hepatitis C virus (HCV) effect and safety of three different oral doses of the cyclophilin inhibitor Debio 025 in combination with pegylated interferon‐α2a (PEG IFN‐α2a) were investigated in a multicenter, randomized, double‐blind, placebo‐controlled escalating dose‐ranging phase II study in treatment‐naïve patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN‐α2a 180 μg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 μg/week PEG IFN‐α2a. In patients with genotypes 1 and 4, the 600‐ and 1,000‐mg combination treatments induced a continuous decay in viral load that reached −4.61 ± 1.88 and −4.75 ± 2.19 log 10 IU/mL at week 4, respectively. In patients with genotypes 2 and 3, HCV RNA levels at week 4 were reduced by −5.91 ± 1.11 and −5.89 ± 0.43 log 10 IU/mL, respectively, with the same treatment regimens. Adverse events were comparable between treatment groups apart from a higher incidence of neutropenia associated with PEG IFN‐α2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day). Conclusion: These results confirm that Debio 025 has a potent activity and an additive effect on HCV RNA reduction in genotype 1 and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN‐α2a. (H EPATOLOGY 2009.)