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


CONCLUSIONS
AVI-005 demonstrates biological activity and pharmaco-kinetic properties in humans that support further development.
Patel
T B
TB
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Pequignot
E
E
Parker
S H
SH
Leavitt
M C
MC
Greenberg
H E
HE
Kraft
W K
WK
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D000328:Adult; D000818:Animals; D030801:Animals, Genetically Modified; D002645:Chickens; D005260:Female; D006031:Glycosylation; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D011494:Protein Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D013810:Therapeutic Equivalency; D001613:beta 2-Microglobulin / Q000097:blood
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D019798:Neopterin; D011494:Protein Kinases; D015088:2',5'-Oligoadenylate Synthetase