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Trial of Cinpanemab in Early Parkinson's Disease.
Lang, Anthony E; Siderowf, Andrew D; Macklin, Eric A; Poewe, Werner; Brooks, David J; Fernandez, Hubert H; Rascol, Olivier; Giladi, Nir; Stocchi, Fabrizio; Tanner, Caroline M; Postuma, Ronald B; Simon, David K; Tolosa, Eduardo; Mollenhauer, Brit; Cedarbaum, Jesse M; Fraser, Kyle; Xiao, James; Evans, Karleyton C; Graham, Danielle L; Sapir, Inbal; Inra, Jennifer; Hutchison, R Matthew; Yang, Minhua; Fox, Tara; Budd Haeberlein, Samantha; Dam, Tien.
Afiliação
  • Lang AE; 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 Hosp
  • Siderowf AD; 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 Hosp
  • Macklin EA; 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 Hosp
  • Poewe W; 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 Hosp
  • Brooks DJ; 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 Hosp
  • Fernandez HH; 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 Hosp
  • Rascol O; 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 Hosp
  • Giladi N; 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 Hosp
  • Stocchi F; 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 Hosp
  • Tanner CM; 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 Hosp
  • Postuma RB; 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 Hosp
  • Simon DK; 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 Hosp
  • Tolosa E; 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 Hosp
  • Mollenhauer B; 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 Hosp
  • Cedarbaum JM; 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 Hosp
  • Fraser K; 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 Hosp
  • Xiao J; 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 Hosp
  • Evans KC; 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 Hosp
  • Graham DL; 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 Hosp
  • Sapir I; 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 Hosp
  • Inra J; 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 Hosp
  • Hutchison RM; 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 Hosp
  • Yang M; 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 Hosp
  • Fox T; 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 Hosp
  • Budd Haeberlein S; 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 Hosp
  • Dam T; 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 Hosp
N Engl J Med ; 387(5): 408-420, 2022 08 04.
Article em En | MEDLINE | ID: mdl-35921450
ABSTRACT

BACKGROUND:

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.

METHODS:

In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2122 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).

RESULTS:

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.

CONCLUSIONS:

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 ClinicalTrials.gov number, NCT03318523.).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Alfa-Sinucleína / Anticorpos Monoclonais Humanizados / Antiparkinsonianos Tipo de estudo: Clinical_trials Limite: Humans Idioma: En Revista: N Engl J Med Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Alfa-Sinucleína / Anticorpos Monoclonais Humanizados / Antiparkinsonianos Tipo de estudo: Clinical_trials Limite: Humans Idioma: En Revista: N Engl J Med Ano de publicação: 2022 Tipo de documento: Article