Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA

Jonathan E. Zuckerman, Ismael Gritli, Anthony Tolcher, Jeremy D. Heidel, Dean Lim, Robert Morgan, Bartosz Chmielowski, Antoni Ribas, Mark E. Davis, Yun Yen

研究成果: 雜誌貢獻文章

152 引文 (Scopus)

摘要

Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)-based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase I clinical trial where 24 patients with different cancers were treated with CALAA-01 and compare those results to data obtained from multispecies animal studies to provide a detailed example of translating this class of nanoparticles from animals to humans. The pharmacokinetics of CALAA-01 in mice, rats, monkeys, and humans show fast elimination and reveal that the maximum concentration obtained in the blood after i.v. administration correlates with body weight across all species. The safety profile of CALAA-01 in animals is similarly obtained in humans except that animal kidney toxicities are not observed in humans; this could be due to the use of a predosing hydration protocol used in the clinic. Taken in total, the animal models do appear to predict the behavior of CALAA-01 in humans.

原文英語
頁(從 - 到)11449-11454
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
111
發行號31
DOIs
出版狀態已發佈 - 八月 5 2014

指紋

Nanoparticles
Small Interfering RNA
Polymers
Clinical Trials, Phase I
RNA Interference
Haplorhini
CALAA-01
Neoplasms
Animal Models
Pharmacokinetics
Body Weight
Clinical Trials
Kidney
Safety
Therapeutics

ASJC Scopus subject areas

  • General

引用此文

Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. / Zuckerman, Jonathan E.; Gritli, Ismael; Tolcher, Anthony; Heidel, Jeremy D.; Lim, Dean; Morgan, Robert; Chmielowski, Bartosz; Ribas, Antoni; Davis, Mark E.; Yen, Yun.

於: Proceedings of the National Academy of Sciences of the United States of America, 卷 111, 編號 31, 05.08.2014, p. 11449-11454.

研究成果: 雜誌貢獻文章

Zuckerman, Jonathan E. ; Gritli, Ismael ; Tolcher, Anthony ; Heidel, Jeremy D. ; Lim, Dean ; Morgan, Robert ; Chmielowski, Bartosz ; Ribas, Antoni ; Davis, Mark E. ; Yen, Yun. / Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. 於: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; 卷 111, 編號 31. 頁 11449-11454.
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