Details

Autor(en) / Beteiligte

• Schenk, Dale B
• Koller, Martin
• Ness, Daniel K
• Griffith, Sue G
• Grundman, Michael
• Zago, Wagner
• Soto, Jay
• Atiee, George
• Ostrowitzki, Susanne
• Kinney, Gene G

Titel

First-in-human assessment of PRX002, an anti-[alpha]-synuclein monoclonal antibody, in healthy volunteers

Ist Teil von

• Movement disorders, 2017-02, Vol.32 (2), p.211

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Wiley HSS Collection

Beschreibungen/Notizen

• Background: [alpha]-Synuclein is a major component of pathologic inclusions that characterize Parkinson's disease. PRX002 is an antibody that targets [alpha]-synuclein, and its murine parent antibody 9E4 has been shown in preclinical studies to reduce [alpha]-synuclein pathology and to protect against cognitive and motor deteriorations and progressive neurodegeneration in human [alpha]-synuclein transgenic mice. Methods: This first-in-human, randomized, double-blind, placebo-controlled, phase 1 study assessed the impact of PRX002 administered to 40 healthy participants in 5 ascending-dose cohorts (n=8/cohort) in which participants were randomly assigned to receive a single intravenous infusion of study drug (0.3, 1, 3, 10, or 30mg/kg; n=6/cohort) or placebo (n=2/cohort). Results: PRX002 demonstrated favorable safety, tolerability, and pharmacokinetic profiles at all doses tested, with no immunogenicity. No serious adverse events, discontinuations as a result of adverse events, or dose-limiting toxicities were reported. Serum PRX002 exposure was dose proportional; the average terminal half-life across all doses was 18.2 days. A significant dose-dependent reduction in free serum [alpha]-synuclein (unbound to PRX002) was apparent within 1 hour after PRX002 administration, whereas total [alpha]-synuclein (free plus bound) increased dose-dependently, presumably because of the expected change in kinetics following antibody binding. Conclusions: This study demonstrates that serum [alpha]-synuclein can be safely modulated in a dose-dependent manner after single intravenous infusions of an anti-[alpha]-synuclein antibody. These findings support continued development of PRX002, including further characterization of its safety, tolerability, pharmacokinetics, and pharmacodynamic effects in the central nervous system in patients with Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.