Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration.
Child
Child, Preschool
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
/ administration & dosage
Disease Progression
Drug Administration Schedule
Enzyme Replacement Therapy
/ methods
Female
Humans
Injections, Intraventricular
Male
Neuronal Ceroid-Lipofuscinoses
/ cerebrospinal fluid
Recombinant Proteins
/ administration & dosage
Tripeptidyl-Peptidase 1
/ deficiency
Journal
Clinical and translational science
ISSN: 1752-8062
Titre abrégé: Clin Transl Sci
Pays: United States
ID NLM: 101474067
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
04
08
2020
accepted:
14
10
2020
pubmed:
18
11
2020
medline:
15
12
2021
entrez:
17
11
2020
Statut:
ppublish
Résumé
Cerliponase alfa is recombinant human tripeptidyl peptidase 1 (TPP1) delivered by i.c.v. infusion for CLN2, a pediatric neurodegenerative disease caused by deficiency in lysosomal enzyme TPP1. We report the pharmacokinetics (PK) and pharmacodynamics of cerliponase alfa, the first i.c.v. enzyme replacement therapy, characterized in a phase I/II study. Escalating doses (30-300 mg Q2W) followed by 300 mg Q2W for ≥ 48 weeks were administered in 24 patients aged ≥ 3 years. Concentrations peaked in cerebrospinal fluid (CSF) at the end of ~ 4-hour i.c.v. infusion and 8 hours thereafter in plasma. Plasma exposure was 300-1,000-fold lower than in CSF, with no correlation in the magnitude of peak concentration (C
Identifiants
pubmed: 33202105
doi: 10.1111/cts.12925
pmc: PMC7993266
doi:
Substances chimiques
Recombinant Proteins
0
Tripeptidyl-Peptidase 1
0
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
EC 3.4.14.-
cerliponase alfa
EC 3.4.14.-
TPP1 protein, human
EC 3.4.14.9
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
635-644Informations de copyright
© 2020 BioMarin. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.
Références
J Cereb Blood Flow Metab. 1997 Jul;17(7):713-31
pubmed: 9270488
Mol Genet Metab. 2008 Jun;94(2):222-33
pubmed: 18343701
N Engl J Med. 2018 May 17;378(20):1898-1907
pubmed: 29688815
Biochim Biophys Acta. 2013 Nov;1832(11):1801-6
pubmed: 23602993
Neuropediatrics. 1997 Feb;28(1):6-8
pubmed: 9151309
Toxicol Appl Pharmacol. 2014 May 15;277(1):49-57
pubmed: 24642058
Pediatr Neurol. 2017 Feb;67:23-35
pubmed: 28089765
Pediatr Endocrinol Rev. 2016 Jun;13 Suppl 1:682-8
pubmed: 27491216
Biochem J. 2001 Jul 1;357(Pt 1):49-55
pubmed: 11415435
J Neurosci Res. 2014 Nov;92(11):1591-8
pubmed: 24938720
Value Health. 2015 Sep;18(6):906-14
pubmed: 26409619
Mol Genet Metab. 2015 Feb;114(2):281-93
pubmed: 25257657
Lancet Neurol. 2019 Jan;18(1):107-116
pubmed: 30470609
Clin Ther. 2017 Jan;39(1):118-129.e3
pubmed: 27955919
Cereb Cortex. 1996 Jul-Aug;6(4):551-60
pubmed: 8670681
Biochim Biophys Acta. 2013 Nov;1832(11):1827-30
pubmed: 23542453
Clin Immunol. 2018 Dec;197:68-76
pubmed: 30205177
Fluids Barriers CNS. 2011 Jan 18;8(1):7
pubmed: 21349155
Ann Neurol. 1978 Oct;4(4):345-56
pubmed: 727739