Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration.

ABSTRACT: 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_max ) or area under the concentration-time curve (AUC) among body sites. Ther

SUBMITTER: Kim A 

PROVIDER: S-EPMC7993266 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature