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

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


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: NCT02157714.

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

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Humans
  • Immunoglobulin G / immunology
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Young Adult
  • alpha-Synuclein / blood*
  • alpha-Synuclein / drug effects*
  • alpha-Synuclein / immunology*


  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • SNCA protein, human
  • alpha-Synuclein

Associated data