Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson’s disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson’s disease.
In this phase 2 trial, we randomly assigned participants with early-stage Parkinson’s disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks. The primary end point was the change from baseline to week 52 in the sum of scores on parts I, II, and III of the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS; range, 0 to 236, with higher scores indicating greater impairment). Secondary end points included the dopamine transporter levels in the putamen of the hemisphere ipsilateral to the clinically more affected side of the body, as measured by 123I-ioflupane single-photon-emission computed tomography (SPECT).
A total of 316 participants were enrolled; 105 were assigned to receive placebo, 105 to receive 1500 mg of prasinezumab, and 106 to receive 4500 mg of prasinezumab. The baseline mean MDS-UPDRS scores were 32.0 in the placebo group, 31.5 in the 1500-mg group, and 30.8 in the 4500-mg group, and mean (±SE) changes from baseline to 52 weeks were 9.4±1.2 in the placebo group, 7.4±1.2 in the 1500-mg group (difference vs. placebo, –2.0; 80% confidence interval [CI], –4.2 to 0.2; P=0.24), and 8.8±1.2 in the 4500-mg group (difference vs. placebo, –0.6; 80% CI, –2.8 to 1.6; P=0.72). There was no substantial difference between the active-treatment groups and the placebo group in dopamine transporter levels on SPECT. The results for most clinical secondary end points were similar in the active-treatment groups and the placebo group. Serious adverse events occurred in 6.7% of the participants in the 1500-mg group and in 7.5% of those in the 4500-mg group; infusion reactions occurred in 19.0% and 34.0%, respectively.
Prasinezumab therapy had no meaningful effect on global or imaging measures of Parkinson’s disease progression as compared with placebo and was associated with infusion reactions. (Funded by F. Hoffmann–La Roche and Prothena Biosciences; PASADENA ClinicalTrials.gov number, NCT03100149.)
Funding and Disclosures
Supported by F.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.
We thank all the participants and their families who participated in the trial, and the staff of the clinical trial sites around the world for their ongoing partnership and assistance. We also thank Lisa Michelle Restelli (Roche) and Amanda Gallagher (Chrysalis Medical Communications) for providing medical writing assistance and Megan Speakman (MediTech Media) for providing medical editing assistance with an earlier version of the manuscript; they were funded by F. Hoffmann–La Roche, in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
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