RT Journal Article
T1 First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers
A1 Hernández Jiménez, Macarena
A1 Martín-Vílchez, Samuel
A1 Ochoa, Dolores
A1 Mejía-Abril, Gina
A1 Román, Manuel
A1 Camargo-Mamani, Paola
A1 Luquero-Bueno, Sergio
A1 Jilma, Bernd
A1 Moro Sánchez, María Ángeles
A1 Fernández Gómez-Chacón, Gerónimo Félix
A1 Piñeiro, David
A1 Ribó, Marc
A1 González, Víctor M
A1 Lizasoaín Hernández, Ignacio
A1 Abad-Santos, Francisco
AB ApTOLL is an aptamer that antagonizes Toll-like receptor 4 and improves functional outcomes in models of ischemic stroke and myocardial infarction. The aim of this study was to characterize the safety and pharmacokinetics of ApTOLL in healthy volunteers. A first-in-human dose-ascending, randomized, placebo-controlled phase I clinical trial to assess safety and pharmacokinetics of ApTOLL (30-min infusion intravenously) was performed in 46 healthy adult male volunteers. The study was divided into two parts: part A included seven single ascending dose levels, and part B had one multiple dose cohort. Safety and pharmacokinetic parameters were evaluated. No serious adverse events or biochemistry alterations were detected at any dose nor at any administration pattern studied. Maximum concentration was detected at the end of the infusion and mean half-life was 9.3 h. Interestingly, exposure increased in the first four levels receiving doses from 0.7 mg to 14 mg (AUC of 2,441.26 h∗ng/mL to 23,371.11 h∗ng/mL) but remained stable thereafter (mean of 23,184.61 h∗ng/mL after 70 mg). Consequently, the multiple dose study did not show any accumulation of ApTOLL. These results show an excellent safety and adequate pharmacokinetic profile that, together with the efficacy demonstrated in nonclinical studies, provide the basis to start clinical trials in patients.
PB Cell Press
YR 2022
FD 2022-03-09
LK https://hdl.handle.net/20.500.14352/113553
UL https://hdl.handle.net/20.500.14352/113553
LA eng
NO Hernández-Jiménez M, Martín-Vílchez S, Ochoa D, Mejía-Abril G, Román M, Camargo-Mamani P, Luquero-Bueno S, Jilma B, Moro MA, Fernández G, Piñeiro D, Ribó M, González VM, Lizasoain I, Abad-Santos F. First-in-human phase I clinical trial of a TLR4-binding DNA aptamer, ApTOLL: Safety and pharmacokinetics in healthy volunteers. Mol Ther Nucleic Acids. 2022 Mar 9;28:124-135. doi: 10.1016/j.omtn.2022.03.005. PMID: 35402075; PMCID: PMC8938885.
DS Docta Complutense
RD 21 abr 2025