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Title

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.

Authors

Roslyn Varki, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 132 South 10th Street, 1170 Main Building, Philadelphia, PA 19107, USAFollow
Ed Pequignot, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 132 South 10th Street, 1170 Main Building, Philadelphia, PA 19107, USAFollow
Mark C Leavitt, Synageva Biopharma, 111 Riverbend Road, Athens, GA 30605, USAFollow
Andres Ferber, Cancer Institute of New Jersey at Cooper University Hospital, Camden, NJ 08103, USAFollow
Walter K Kraft, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 132 South 10th Street, 1170 Main Building, Philadelphia, PA 19107, USAFollow

Document Type

Article

Publication Date

1-1-2009

Comments

This article has been peer reviewed and is published in BMC Clinical Pharmacology. Volume 9, 28 January 2009, Article number 2. The published version is available at DOI: 10.1186/1472-6904-9-2. Copyright © BioMed Central Ltd.

Abstract

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.

Recommended Citation

Varki, Roslyn; Pequignot, Ed; Leavitt, Mark C; Ferber, Andres; and Kraft, Walter K, "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." (2009). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 3.
http://jdc.jefferson.edu/petfp/3