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Trial of Cinpanemab in Early Parkinson’s Disease

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.

For re-use rights please refer to the publisher's terms and conditions.


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.

Publication metadata

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


DOI: 10.1056/NEJMoa2203395

ePrints DOI: 10.57711/1323-0g12


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