健康受试者中禽源转基因重组人干扰素α2b（AVI - 005）：一项开放标签、单剂量、对照研究。

Transgenic avian-derived recombinant human interferon-alpha2b (AVI-005) in healthy subjects: an open-label, single-dose, controlled study.

作者信息

Patel T B, Pequignot E, Parker S H, Leavitt M C, Greenberg H E, Kraft W K

机构信息

Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

Int J Clin Pharmacol Ther. 2007 Mar;45(3):161-8. doi: 10.5414/cpp45161.

DOI:10.5414/cpp45161

PMID:17416111

Abstract

BACKGROUND/AIMS: This study characterized the safety and pharmacological properties of AVI-005, a novel glycosylated recombinant human interferon-alpha2b produced from the egg whites of chickens transfected with human cDNA.

METHODS

18 healthy volunteers received single subcutaneous rising doses (0.5, 1.66 or 5 million international units, MIU) of AVI-005. A randomized parallel comparator group of 10 subjects received 5 MIU of unglycosylated IFN-alpha2b (Intron A). The pharmacokinetic parameters t1/2, tmax, Cmax, AUC0-24h, Vd, and clearance were compared between AVI-005 and unglycosylated IFN-alpa2b.

RESULTS

At equipotent doses, AVI-005 had a larger AUC0-24h than the control interferon. Pharmacodynamic markers ofneopterin and beta2-microglobulin for the two treatments were similar. These markers were increased by AVI-005 in a dose-dependent manner. Pharmacodynamic responses to treatment with AVI-005 were shown by the change in mRNA expression for interferon inducible protein kinase and 2'5'-oligoadenylate synthetase. Adverse events in the two groups were qualitatively and quantitatively similar.

CONCLUSION

AVI-005 demonstrates biological activity and pharmaco-kinetic properties in humans that support further development.

摘要

背景/目的：本研究对AVI - 005的安全性和药理学特性进行了表征，AVI - 005是一种通过转染人cDNA的鸡的蛋清生产的新型糖基化重组人干扰素α2b。

方法

18名健康志愿者接受了单次皮下递增剂量（0.5、1.66或500万国际单位，MIU）的AVI - 005。一个由10名受试者组成的随机平行对照组接受了5 MIU的非糖基化干扰素α2b（安福隆）。比较了AVI - 005和非糖基化干扰素α2b之间的药代动力学参数t1/2、tmax、Cmax、AUC0 - 24h、Vd和清除率。

结果

在等效剂量下，AVI - 005的AUC0 - 24h比对照干扰素更大。两种治疗方法的新蝶呤和β2 - 微球蛋白的药效学标志物相似。这些标志物在AVI - 005作用下呈剂量依赖性增加。AVI - 005治疗的药效学反应通过干扰素诱导蛋白激酶和2'5'-寡腺苷酸合成酶的mRNA表达变化得以体现。两组的不良事件在性质和数量上相似。