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Clinical Trial
. 2017 Feb;32(2):211-218.
doi: 10.1002/mds.26878. Epub 2016 Nov 25.

First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers

Dale B Schenk  1 , Martin Koller  1 , Daniel K Ness  1 , Sue G Griffith  2 , Michael Grundman  3   4 , Wagner Zago  1 , Jay Soto  1 , George Atiee  5 , Susanne Ostrowitzki  6 , Gene G Kinney  1
Affiliations
Clinical Trial

First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers

Dale B Schenk et al. Mov Disord. 2017 Feb.

Abstract

Background: α-Synuclein is a major component of pathologic inclusions that characterize Parkinson's disease. PRX002 is an antibody that targets α-synuclein, and its murine parent antibody 9E4 has been shown in preclinical studies to reduce α-synuclein pathology and to protect against cognitive and motor deteriorations and progressive neurodegeneration in human α-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 30 mg/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 α-synuclein (unbound to PRX002) was apparent within 1 hour after PRX002 administration, whereas total α-synuclein (free plus bound) increased dose-dependently, presumably because of the expected change in kinetics following antibody binding.

Conclusions: This study demonstrates that serum α-synuclein can be safely modulated in a dose-dependent manner after single intravenous infusions of an anti-α-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.

Trial registration: ClinicalTrials.gov NCT02157714.

Keywords: Parkinson's disease; clinical trial; protein aggregation; protein misfolding; synucleinopathy.

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Figures

Figure 1
Figure 1
Pharmacokinetics of PRX002. Serum PRX002 concentration–time profiles after a single dose of PRX002.
Figure 2
Figure 2
Pharmacodynamics of PRX002. Change from baseline of serum‐free α‐synuclein after a single dose of PRX002.
See this image and copyright information in PMC

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