Flisiak Robert, Feinman Saya V, Jablkowski Maciej, Horban Andrzej, Kryczka Wieslaw, Pawlowska Małgorzata, Heathcote Jenny E, Mazzella Giuseppe, Vandelli Carmen, Nicolas-Métral Valérie, Grosgurin Pierre, Liz Jorge S, Scalfaro Pietro, Porchet Hervé, Crabbé Raf
Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
Hepatology. 2009 May;49(5):1460-8. 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-alpha2a (PEG IFN-alpha2a) 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-alpha2a 180 microg/week for 4 weeks were compared with monotherapy with either 1,000 mg/day Debio 025 or 180 microg/week PEG IFN-alpha2a. 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-alpha2a and an increased incidence of isolated hyperbilirubinemia at the highest dose of Debio 025 (1,000 mg/day).
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-alpha2a.
在一项针对初治慢性丙型肝炎患者的多中心、随机、双盲、安慰剂对照的剂量递增II期研究中，研究了三种不同口服剂量的亲环素抑制剂Debio 025与聚乙二醇化干扰素-α2a（PEG IFN-α2a）联合使用时的抗丙型肝炎病毒（HCV）效果及安全性。将每天200、600和1000毫克Debio 025与每周180微克PEG IFN-α2a联合使用4周的剂量，与每天1000毫克Debio 025或每周180微克PEG IFN-α2a的单药治疗进行比较。在基因1型和4型患者中，600毫克和1000毫克联合治疗组在第4周时病毒载量持续下降，分别达到-4.61±1.88和-4.75±2.19 log(10) IU/mL。在基因2型和3型患者中，相同治疗方案在第4周时HCV RNA水平分别降低了-5.91±1.11和-5.89±0.43 log(10) IU/mL。除了与PEG IFN-α2a相关的中性粒细胞减少发生率较高以及Debio 025最高剂量（每天1000毫克）时孤立性高胆红素血症发生率增加外，各治疗组之间不良事件相当。
这些结果证实，当与PEG IFN-α2a联合使用时，Debio 025在每天600毫克和1000毫克剂量下对基因1型和4型患者的HCV RNA减少具有强效活性和相加作用。
