糖基化重组人粒细胞集落刺激因子在一种新的蛋白质生产系统(AVI-014)中在健康受试者中产生:首次人类单剂量对照研究。

Roslyn Varki, Ed Pequignot, Mark C Leavitt, Andres Ferber, Walter K Kraft
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引用次数: 8

摘要

背景:AVI-014是一种源自蛋清的重组人粒细胞集落刺激因子(G-CSF)。这项健康志愿者研究是对AVI-014的首次人体调查。方法:24名男性和女性受试者接受单次皮下注射4或8 mcg/kg的AVI-014。16名对照受试者以部分盲法平行方式接受4或8 mcg/kg非格司汀(Neupogen, Amgen)。结果:4 mcg/kg avii -014/非格司汀AUC(0-72 hr)的几何平均比(GMR) (90% CI)为1.00 (0.76,1.31),Cmax为0.86(0.66,1.13)。在8 mcg/kg剂量下,AUC(0-72) GMR为0.89 (0.69,1.14),Cmax为0.76(0.58,0.98)。先验药代动力学生物等效性定义为GMR的90% CI范围为0.8-1.25。在4和8 mcg/kg时,白细胞和绝对中性粒细胞计数增加曲线下的面积(AUC)(0-9天)和Cmax(比基线增加的最大百分比)GMR均降至药效学生物等效性的0.5-2.0先验范围内。两种剂量的cd34 + %增加曲线AUC(0-9天)和Cmax GMR约为1,但由于固有方差,90%置信区间较大,该测量不符合药效学生物等效性。AVI-014显示出与非格拉西汀相似的副作用。结论:在健康志愿者中,avii -014具有与非格拉西汀相当的安全性、药代动力学和药效学特性。这些发现支持了对AVI-014的进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study.

A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study.

A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study.

A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study.

Background: AVI-014 is an egg white-derived, recombinant, human granulocyte colony-stimulating factor (G-CSF). This healthy volunteer study is the first human investigation of AVI-014.

Methods: 24 male and female subjects received a single subcutaneous injection of AVI-014 at 4 or 8 mcg/kg. 16 control subjects received 4 or 8 mcg/kg of filgrastim (Neupogen, Amgen) in a partially blinded, parallel fashion.

Results: The Geometric Mean Ratio (GMR) (90% CI) of 4 mcg/kg AVI-014/filgrastim AUC(0-72 hr) was 1.00 (0.76, 1.31) and Cmax was 0.86 (0.66, 1.13). At the 8 mcg/kg dose, the AUC(0-72) GMR was 0.89 (0.69, 1.14) and Cmax was 0.76 (0.58, 0.98). A priori pharmacokinetic bioequivalence was defined as the 90% CI of the GMR bounded by 0.8-1.25. Both the white blood cell and absolute neutrophil count area under the % increase curve AUC(0-9 days) and Cmax (maximal % increase from baseline)GMR at 4 and 8 mcg/kg fell within the 0.5-2.0 a priori bound set for pharmacodynamic bioequivalence. The CD 34+ % increase curve AUC(0-9 days) and Cmax GMR for both doses was approximately 1, but 90% confidence intervals were large due to inherent variance, and this measure did not meet pharmacodynamic bioequivalence. AVI-014 demonstrated a side effect profile similar to that of filgrastim.

Conclusion: AVI-014 has safety, pharmacokinetic, and pharmacodynamic properties comparable to filgrastim at an equal dose in healthy volunteers. These findings support further investigation in AVI-014.

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