The Cyclophilin Inhibitor Debio 025 Combined with PEG IFN alpha 2a Significantly Reduces Viral Load in Treatment-Naive Hepatitis C Patients

作者：Flisiak Robert; Feinman Saya V; Jablkowski Maciej; Horban Andrzej; Kryczka Wieslaw; Pawlowska Malgorzata; Heathcote Jenny E; Mazzella Giuseppe; Vandelli Carmen; Nicolas Metral Valerie; Grosgurin Pierre; Liz Jorge S; Scalfaro Pietro; Porchet Herve; Crabbe Raf^*

来源：Hepatology, 2009, 49(5): 1460-1468.

DOI：10.1002/hep.22835

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-alpha 2a (PEG IFN-alpha 2a) were investigated in a multicenter, randomized, double-blind, placebo-controlled escalating dose-ranging phase 11 study in treatment-naive patients with chronic hepatitis C. Doses of 200, 600, and 1,000 mg/day Debio 025 in combination with PEG IFN-alpha 2a 180 mu g/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 mu g/week PEG IFN-alpha 2a. In patients with genotypes I 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-alpha 2a 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 I and 4 patients at 600 and 1,000 mg/day when combined with PEG IFN-alpha 2a. (HEPATOLOGY 2009;49:1460-1468.)

• 出版日期2009-5