165174 20230915090609.0 10.1056/NEJMoa2202867 doi pmid:35921451 pmid 0028-4793 ISSN 1533-4406 ISSN altmetric:133617507 altmetric DZNE-2022-01476 English 610 Pagano, Gennaro 0 Trial of Prasinezumab in Early-Stage Parkinson's Disease. Waltham, Mass. 2022 MMS article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1663928346_2409 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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.). 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Antibodies, Monoclonal, Humanized NLM Chemicals Antiparkinson Agents NLM Chemicals Dopamine Plasma Membrane Transport Proteins NLM Chemicals alpha-Synuclein NLM Chemicals Antibodies, Monoclonal, Humanized: therapeutic use MeSH Antiparkinson Agents: therapeutic use MeSH Dopamine Plasma Membrane Transport Proteins: therapeutic use MeSH Double-Blind Method MeSH Humans MeSH Parkinson Disease: drug therapy MeSH Treatment Outcome MeSH alpha-Synuclein: antagonists & inhibitors MeSH Taylor, Kirsten I 1 Anzures-Cabrera, Judith 2 Marchesi, Maddalena 3 Simuni, Tanya 4 Marek, Kenneth P:(DE-2719)9000201 5 dzne Postuma, Ronald B 6 Pavese, Nicola 7 Stocchi, Fabrizio 8 Azulay, Jean-Philippe 9 Mollenhauer, Brit P:(DE-2719)9001340 10 dzne López-Manzanares, Lydia 11 Russell, David S 12 Boyd, James T 13 Nicholas, Anthony P 14 Luquin, María R 15 Hauser, Robert A 16 Gasser, Thomas P:(DE-2719)2320009 17 dzne Poewe, Werner 18 Ricci, Benedicte 19 Boulay, Anne 20 Vogt, Annamarie 21 Boess, Frank G 22 Dukart, Juergen 23 D'Urso, Giulia 24 Finch, Rebecca 25 Zanigni, Stefano 26 Monnet, Annabelle 27 Pross, Nathalie 28 Hahn, Andrea 29 Svoboda, Hanno 30 Britschgi, Markus 31 Lipsmeier, Florian 32 Volkova-Volkmar, Ekaterina 33 Lindemann, Michael 34 Dziadek, Sebastian 35 Holiga, Štefan 36 Rukina, Daria 37 Kustermann, Thomas 38 Kerchner, Geoffrey A 39 Fontoura, Paulo 40 Umbricht, Daniel 41 Doody, Rachelle 42 Nikolcheva, Tania 43 Bonni, Azad 44 Investigators, PASADENA 45 Collaboration Author Group, Prasinezumab Study 46 Collaboration Author 10.1056/NEJMoa2202867 Vol. 387, no. 5, p. 421 - 432 PERI:(DE-600)1468837-2 5 421 - 432 The New England journal of medicine 387 2022 0028-4793 oai:pub.dzne.de:165174 VDB External Institute I:(DE-HGF)0 Extern 5 P:(DE-2719)9000201 External Institute I:(DE-HGF)0 Extern 10 P:(DE-2719)9001340 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 17 P:(DE-2719)2320009 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2022 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2021-02-04 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2021-02-04 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2021-02-04 JCR StatID:(DE-HGF)0100 StatID NEW ENGL J MED : 2021 2022-11-05 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-05 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-05 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-05 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-05 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-05 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-05 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-05 DBCoverage StatID:(DE-HGF)1110 StatID Current Contents - Clinical Medicine 2022-11-05 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-05 IF >= 90 StatID:(DE-HGF)9990 StatID NEW ENGL J MED : 2021 2022-11-05 I:(DE-2719)1210000 AG Gasser Parkinson Genetics 0 journal VDB I:(DE-2719)1210000-7 UNRESTRICTED