A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data.

Autor:	Pagano G; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Boess FG; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Taylor KI; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland.; Faculty of Psychology, University of Basel, Basel, Switzerland., Ricci B; Roche Pharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Mollenhauer B; Paracelsus-Elena-Klinik, Kassel, Germany.; Department of Neurology, University Medical Center Göttingen, Göttingen, Germany., Poewe W; Department of Neurology, Innsbruck Medical University, Innsbruck, Austria., Boulay A; Idorisa Pharmaceuticals Ltd., Allschwil, Switzerland., Anzures-Cabrera J; Roche Products Ltd., Welwyn Garden City, United Kingdom., Vogt A; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Marchesi M; Roche Pharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Post A; Feetme SAS, Paris, France., Nikolcheva T; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Kinney GG; Prothena Biosciences Inc., South San Francisco, CA, United States., Zago WM; Prothena Biosciences Inc., South San Francisco, CA, United States., Ness DK; Prothena Biosciences Inc., South San Francisco, CA, United States., Svoboda H; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Britschgi M; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Ostrowitzki S; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Simuni T; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States., Marek K; Institute for Neurodegenerative Disorders, New Haven, CT, United States., Koller M; Prothena Biosciences Inc., South San Francisco, CA, United States., Sevigny J; Prevail Therapeutics, New York, NY, United States., Doody R; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Fontoura P; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Umbricht D; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Bonni A; Roche Pharma Research and Early Development (pRED), Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2021 Oct 01; Vol. 12, pp. 705407. Date of Electronic Publication: 2021 Oct 01 (Print Publication: 2021).
DOI:	10.3389/fneur.2021.705407
Abstrakt:	Background: Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. Objective: The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. Methods: The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study. Individuals with early PD, recruited across the US and Europe, received monthly intravenous doses of prasinezumab (1,500 or 4,500 mg) or placebo for a 52-week period (Part 1), followed by a 52-week extension (Part 2) in which all participants received active treatment. Key inclusion criteria were: aged 40-80 years; Hoehn & Yahr (H&Y) Stage I or II; time from diagnosis ≤2 years; having bradykinesia plus one other cardinal sign of PD (e.g., resting tremor, rigidity); DAT-SPECT imaging consistent with PD; and either treatment naïve or on a stable monoamine oxidase B (MAO-B) inhibitor dose. Study design assumptions for sample size and study duration were built using a patient cohort from the Parkinson's Progression Marker Initiative (PPMI). In this report, baseline characteristics are compared between the treatment-naïve and MAO-B inhibitor-treated PASADENA cohorts and between the PASADENA and PPMI populations. Results: Of the 443 patients screened, 316 were enrolled into the PASADENA study between June 2017 and November 2018, with an average age of 59.9 years and 67.4% being male. Mean time from diagnosis at baseline was 10.11 months, with 75.3% in H&Y Stage II. Baseline motor and non-motor symptoms (assessed using Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS]) were similar in severity between the MAO-B inhibitor-treated and treatment-naïve PASADENA cohorts (MDS-UPDRS sum of Parts I + II + III [standard deviation (SD)]; 30.21 [11.96], 32.10 [13.20], respectively). The overall PASADENA population (63.6% treatment naïve and 36.4% on MAO-B inhibitor) showed a similar severity in MDS-UPDRS scores (e.g., MDS-UPDRS sum of Parts I + II + III [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD. Trial Registration: NCT03100149. Competing Interests: GP, FB, KT, BR, JA-C, AV, MM, TN, HS, MB, SO, RD, DU, and ABon are employees of F. Hoffmann-La Roche Ltd. ABou is an employee of Idorsia Pharmaceuticals Ltd. AP is an employee of Feetme SAS. JS is an employee of Prevail Therapeutics. GK, WZ, DN, and MK are employees of Prothena Biosciences Inc. The authors declare that F. Hoffmann-La Roche Ltd was the sponsor of the study. F. Hoffmann-La Roche Ltd and Prothena Corporation plc were the funders of the study. F. Hoffmann-La Roche Ltd and Prothena Corporation plc were involved in the study design, collection, analysis, interpretation of data, the writing of this article and the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Pagano, Boess, Taylor, Ricci, Mollenhauer, Poewe, Boulay, Anzures-Cabrera, Vogt, Marchesi, Post, Nikolcheva, Kinney, Zago, Ness, Svoboda, Britschgi, Ostrowitzki, Simuni, Marek, Koller, Sevigny, Doody, Fontoura, Umbricht, Bonni and PASADENA Investigators and Prasinezumab Study Group.)
Databáze:	MEDLINE
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