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Lookup NU author(s): Professor David BrooksORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Massachusetts Medical Society, 2022.
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BACKGROUND Aggregated α-synuclein plays an important role in Parkinson disease (PD) pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, was evaluated as a potential disease-modifying treatment for PD. METHODS Participants with early PD were randomly assigned in a 2:1:2:2 ratio to receive intravenous infusions of placebo, cinpanemab 250 mg, 1250 mg or 3500 mg every 4 weeks in a phase 2, 52-week, multicenter, double-blind, trial, followed by an active-treatment dose-blinded extension period, for a total of up to 112 weeks. The primary outcome was change from baseline in the Movement Disorder Society Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDSS-UPDRS) total score (Parts I+II+III, range, 0 to 236 , higher scores indicating worse performance). Secondary outcomes included the subscales of MDS-UPDRS and dopamine transporter single-photon emission computerized tomography (DaT-SPECT). RESULTS A total of 357 participants were enrolled. The 52-week double-blind period was completed, but the extension period was not completed as planned due to lack of efficacy. The change from baseline to Week 52 in the primary endpoint was 10.8, 10.5, 11.3, and 10.9 points for placebo and the 3 doses of cinpanemab, respectively (difference 250 mg vs. placebo,−0.30; 95% confidence interval [CI], −4.89 to 4.29; P =0.90; (difference 1250 mg vs placebo, 0.50; 95% CI, −3.31 to 4.31; P=0.80; difference 3500 mg vs placebo, 0.08; 95% CI, −3.81 to 3.96; P=0.97). There was no difference in this endpoint between groups at 72 weeks. Secondary outcomes were similar to the negative results of the primary outcome. Single-photon emission computed tomography imaging of the dopamine transporter striatal binding ratio showed no differences between placebo and any cinpanemab group at Week 52. During the placebo-controlled period , the most common AEs in study participants receiving cinpanemab were headache, nasopharyngitis, and fall; most were mild to moderate in severity. The rates of infusion reactions were low. CONCLUSIONS Cinpanemab had no beneficial effect on measures of progression of clinical severity in early PD or on DaT-SPECT imaging.
Author(s): Lang AE, Siderowf AD, Macklin EA, Poewe W, Brooks DJ, Fernandez HH, Rascol O, Giladi N, Stocchi F, Tanner CM, Postuma RB, Simon DK, Tolosa E, Mollenhauer B, Cedarbaum JM, Fraser K, Xiao J, Evans KC, Graham DL, Sapir I, Inra J, Hutchison RM, Yang M, Fox T, Haeberlein SB, Dam T
Publication type: Article
Publication status: Published
Journal: New England Journal of Medicine
Year: 2022
Volume: 387
Pages: 408-420
Print publication date: 04/08/2022
Online publication date: 04/08/2022
Acceptance date: 25/05/2022
Date deposited: 25/05/2022
ISSN (print): 0028-4793
ISSN (electronic): 1533-4406
Publisher: Massachusetts Medical Society
URL: https://doi.org/10.1056/NEJMoa2203395
DOI: 10.1056/NEJMoa2203395
ePrints DOI: 10.57711/1323-0g12
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