A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients
A phase 2 study to evaluate the antiviral activity, safety, and pharmacokinetics of recombinant human albumin-interferon alfa fusion protein in genotype 1 chronic hepatitis C patients
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DOI：
10.1016/j.jhep.2005.12.011
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发表时间：
2006-04-01
影响因子：
25.7
通讯作者：
Subramanian, GM
中科院分区：
文献类型：
--
作者：
Bain, VG;Kaita, KD;Subramanian, GM
背景/目的：重组人白蛋白-干扰素α是一种新型的85.7 kD重组蛋白，由干扰素α-2b与人血清白蛋白基因融合而成。方法：对干扰素阴性的慢性丙型肝炎患者进行2期开放标记剂量范围研究，以评价其抗病毒活性、安全性和药代动力学。56例患者接受了间隔14天的两次白干扰素皮下注射，剂量分别为200、450、670、900和1200微克。结果：在接受900和1200微克的高剂量干扰素的患者中，69%(18/26)的患者在第4周时丙型肝炎病毒(HCVRNA)下降了2log(10IU/mL)或以上，而这两个高剂量队列的患者在第4周时丙型肝炎病毒RNA的平均降幅为3.2log(10IU/mL)。病毒动力学模型显示了一种剂量依赖的双相反应。不良反应的严重程度大多在轻度到中度之间。最常见的不良反应是头痛(73%)、寒战(63%)、乏力(61%)和关节痛(55%)。Alb-干扰素的中位终末半衰期为141h，与既往有干扰素-α-干扰素治疗经验的患者的数据一致。结论：丙型-干扰素在丙型肝炎病毒1型感染患者中具有显著的抗病毒活性，耐受性良好。(C)2006年欧洲肝脏研究协会。爱思唯尔出版，版权所有。
Background/Aims: Recombinant human albumin-interferon alfa (alb-IFN) is a novel 85.7-kD recombinant protein consisting of interferon alfa-2b genetically fused to human serum albumin.Methods: A phase 2, open-label, dose-ranging study was conducted in IFN-alfa-naive patients with genotype 1 chronic hepatitis C to evaluate the antiviral activity, safety, and pharmacokinetics of alb-IFN. Fifty-six patients were enrolled to receive two subcutaneous injections of alb-IFN 14 days apart in five dose cohorts of 200, 450, 670, 900, and 1200 mu g.Results: A 2 log(10) IU/mL or greater reduction in hepatitis C virus (HCV) RNA at Week 4 was observed in 69% (18/26) of patients who received the higher alb-IFN doses of 900 and 1200 mu g. The mean HCV RNA reduction at Week 4 in these two higher-dose cohorts was 3.2 log(10) IU/mL. Modeling of viral kinetics demonstrated a biphasic response that was dose dependent. Adverse events were mostly mild to moderate in severity. The most common adverse events were headache (73%), chills (63%), fatigue (61%), and arthralgia (55%). The median terminal half-life was 141 h consistent with previous alb-IFN data from IFN-alfa-experienced patients.Conclusions: Alb-IFN demonstrated significant antiviral activity and was well tolerated in patients with HCV genotype 1 infection. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.