Evidence map›Paper›PMID 25049380›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

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

Open access · bronzeAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed
15.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

161 citing papers in PubMed, 398 citations in OpenAlex.

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  4. Therapy resistance-related ncRNAs in cervical cancer: biomarkers and therapeutic targets.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026
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101 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 2 countries.

Jonathan E ZuckermanChemical Engineering, California Institute of Technology, Pasadena, CA 91125;
Ismael GritliCollege of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan;
Anthony TolcherSouth Texas Accelerated Research Therapeutics, San Antonio, TX 78229;
Jeremy D HeidelInformulate, Madison, WI 53704;
Dean LimDepartment of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010;
Robert MorganDepartment of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010;
Bartosz ChmielowskiDepartment of Medicine, Division of Hematology Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; and.
Antoni RibasDepartment of Medicine, Division of Hematology Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; andJonsson Comprehensive Cancer Center, Los Angeles, CA 90095.
Mark E DavisChemical Engineering, California Institute of Technology, Pasadena, CA 91125; mdavis@cheme.caltech.edu yyen@coh.org.
Yun YenCollege of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan;Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA 91010; mdavis@cheme.caltech.edu yyen@coh.org.
California Institute of Technology · USCity of Hope · USTaipei Medical University · TWEmulate (United States) · USSouth Texas Accelerated Research Therapeutics · USUCLA Jonsson Comprehensive Cancer CenterUniversity of California, Los Angeles · US

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
NIGMS NIH HHS GM08042NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

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.

Indexed as

AgedAged, 80 and overAnimalsBlood CoagulationComplement System ProteinsCytokinesDemographyFemaleHaplorhiniHumansImmunizationKidneyLiverMaleMiceMiddle AgedCALAA-01Complement System ProteinsCytokinesPolyethylene GlycolsPolymersRNA, Small InterferingDNA proliferationDNA replicationdose limiting toxicitymaximum tolerance dosetranslational medicine

Identifiers

PMID25049380
PMCPMC4128111
OpenAlexW2055631278

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.