학술논문
A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
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article
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Pagano, Gennaro; Boess, Frank G; Taylor, Kirsten I; Ricci, Benedicte; Mollenhauer, Brit; Poewe, Werner; Boulay, Anne; Anzures-Cabrera, Judith; Vogt, Annamarie; Marchesi, Maddalena; Post, Anke; Nikolcheva, Tania; Kinney, Gene G; Zago, Wagner M; Ness, Daniel K; Svoboda, Hanno; Britschgi, Markus; Ostrowitzki, Susanne; Simuni, Tanya; Marek, Kenneth; Koller, Martin; Sevigny, Jeff; Doody, Rachelle; Fontoura, Paulo; Umbricht, Daniel; Bonni, Azad; Investigators, PASADENA; Group, Prasinezumab Study; Altendorf, Claudia; Anandan, Chareyna; Andrews, Giulia; Ansquer, Solène; Arrouasse, Raphaele; Aslam, Sana; Azulay, Jean-Philippe; Baker, Jeanette; Martinez, Ernest Balaguer; Barbu, Shadi; Bardram, Kara; Bega, Danny; Marco, Helena Bejr-Kasem; Benatru, Isabelle; Benchetrit, Eve; Bernhard, Felix; Besharat, Amir; Bette, Sagari; Bichon, Amelie; Billnitzer, Andrew; Blondeau, Sophie; Boraud, Thomas; Borngräber, Freiderike; Boyd, James; Brockmann, Kathrin; Brodsky, Matthew; Brown, Ethan; Bruecke, Christof; Calvas, Fabienne; Canelo, Monica; Carbone, Federico; Carroll, Claire; Fernandez, Laura Casado; Cassé-Perrot, Catherine; Castrioto, Anna; Catala, Helene; Chan, Justine; Cheriet, Samia; Ciabarra, Anthony; Classen, Joseph; Coleman, Juliana; Coleman, Robert; Compta, Yaroslau; Corbillé, Anne-Gaëlle; Corvol, Jean-Christophe; Cosgaya, Mariana; Dahodwala, Nabila; Damier, Philippe; David, Elodie; Davis, Thomas; Dean, Marissa; Debilly, Berengere; DeGiorgio, Janell; Deik, Andres; Delaby, Laure; Delfini, Marie-Helene; Derkinderen, Pascal; Derost, Philipp; de Toledo, Maria; Deuel, Lisa; Diaz-Hernandez, Ann Marie; Dietiker, Cameron; Dimenshteyn, Karina; Dotor, Julio; Durif, Franck; Ebentheuer, Jens; Eggert, Karla Maria; Madueño, Sara Eichau; Eickhoff, Claudia; Ellenbogen, Aaron; Ellmerer, Philipp; Vazquez, Ines Esparragosa
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Abstract
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.