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Trial of Cinpanemab in Early Parkinson’s Disease

List of authors.
  • Anthony E. Lang, M.D.,
  • Andrew D. Siderowf, M.D.,
  • Eric A. Macklin, Ph.D.,
  • Werner Poewe, M.D.,
  • David J. Brooks, M.D., D.Sc.,
  • Hubert H. Fernandez, M.D.,
  • Olivier Rascol, M.D.,
  • Nir Giladi, M.D.,
  • Fabrizio Stocchi, M.D.,
  • Caroline M. Tanner, M.D., Ph.D.,
  • Ronald B. Postuma, M.D.,
  • David K. Simon, M.D., Ph.D.,
  • Eduardo Tolosa, M.D.,
  • Brit Mollenhauer, M.D.,
  • Jesse M. Cedarbaum, M.D.,
  • Kyle Fraser, Ph.D.,
  • James Xiao, Ph.D.,
  • Karleyton C. Evans, M.D.,
  • Danielle L. Graham, Ph.D.,
  • Inbal Sapir, Ph.D.,
  • Jennifer Inra, M.D.,
  • R. Matthew Hutchison, Ph.D.,
  • Minhua Yang, M.S.,
  • Tara Fox, M.S.,
  • Samantha Budd Haeberlein, Ph.D.,
  • and Tien Dam, M.D.
  • for the SPARK Investigators*



Aggregated α-synuclein plays an important role in Parkinson’s disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson’s disease.


Download a PDF of the Research Summary.

In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson’s disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks. The primary end points were the changes from baseline in the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary end points included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT).


Of the 357 enrolled participants, 100 were assigned to the control group, 55 to the 250-mg cinpanemab group, 102 to the 1250-mg group, and 100 to the 3500-mg group. The trial was stopped after the week 72 interim analysis owing to lack of efficacy. The change to week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, −0.3 points [95% confidence interval {CI}, −4.9 to 4.3], P=0.90; 0.5 points [95% CI, −3.3 to 4.3], P=0.80; and 0.1 point [95% CI, −3.8 to 4.0], P=0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was −0.9 points (95% CI, −5.6 to 3.8) for the 250-mg dose, 0.6 points (95% CI, −3.3 to 4.4) for the 1250-mg dose, and −0.8 points (95% CI, −4.6 to 3.0) for the 3500-mg dose. Results for secondary end points were similar to those for the primary end points. DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis, and falls.


In participants with early Parkinson’s disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. (Funded by Biogen; SPARK number, NCT03318523.)

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Cinpanemab in Early Parkinson’s Disease

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Funding and Disclosures

Supported by Biogen.

Disclosure forms provided by the authors are available with the full text of this article at

A data sharing statement provided by the authors is available with the full text of this article at

We thank the trial coordinators, staff, and participants for their contributions to the trial; patient advocate Michael Byrne for providing trial input; and Linda Wagner and Cara Dickinson, of Excel Scientific Solutions, for writing and editorial support with an earlier version of the manuscript.

Author Affiliations

From the Edmond J. Safra Program in Parkinson’s Disease, University Health Network, and the University of Toronto, Toronto (A.E.L.), and the Montreal Neurological Institute, Montreal (R.B.P.); the University of Pennsylvania, Philadelphia (A.D.S.); the Biostatistics Center, Massachusetts General Hospital (E.A.M.), Beth Israel Deaconess Medical Center (D.K.S.), and Harvard Medical School (E.A.M., D.K.S.), Boston, and Biogen, Cambridge (K.F., J.X., K.C.E., D.L.G., I.S., J.I., R.M.H., M.Y., S.B.H., T.D.) — all in Massachusetts; Medizinische Universität Innsbruck, Innsbruck, Austria (W.P.); Newcastle University, Newcastle upon Tyne (D.J.B.), and Biogen, Maidenhead (T.F.) — both in the United Kingdom; Aarhus University, Aarhus, Denmark (D.J.B.); the Center for Neurological Restoration, Cleveland Clinic, and Cleveland Clinic Lerner College of Medicine — both in Cleveland (H.H.F.); Clinical Investigation Center 1436, the Departments of Clinical Pharmacology and Neurosciences, NS-PARK–French Clinical Research Infrastructure Network, NeuroToul COEN Center, INSERM, University Hospital of Toulouse, and the University of Toulouse III — both in Toulouse, France (O.R.); Tel Aviv Sourasky Medical Center, and the Sackler School of Medicine and the Sagol School of Neuroscience, Tel Aviv University — both in Tel Aviv, Israel (N.G.); University San Raffaele and IRCCS San Raffaele — both in Rome (F.S.); the University of California, San Diego, La Jolla (C.M.T.), and the San Francisco Veterans Affairs Medical Center, San Francisco (C.M.T.); the University of Barcelona, Barcelona (E.T.); the Department of Neurology, University Medical Center Göttingen, Göttingen, and Paracelsus-Elena-Klinik, Kassel — both in Germany (B.M.); and Coeruleus Clinical Sciences, Woodbridge, CT (J.M.C.).

Dr. Dam can be contacted at or at Biogen, 225 Binney St., Cambridge, MA 02142.

A complete list of the investigators in the SPARK trial is provided in the Supplementary Appendix, available at