학술논문
A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
Document Type
article
Author
Gennaro Pagano; Frank G. Boess; Kirsten I. Taylor; Benedicte Ricci; Brit Mollenhauer; Werner Poewe; Anne Boulay; Judith Anzures-Cabrera; Annamarie Vogt; Maddalena Marchesi; Anke Post; Tania Nikolcheva; Gene G. Kinney; Wagner M. Zago; Daniel K. Ness; Hanno Svoboda; Markus Britschgi; Susanne Ostrowitzki; Tanya Simuni; Kenneth Marek; Martin Koller; Jeff Sevigny; Rachelle Doody; Paulo Fontoura; Daniel Umbricht; Azad Bonni; PASADENA Investigators; Prasinezumab Study Group; Claudia Altendorf; Chareyna Anandan; Giulia Andrews; Solène Ansquer; Raphaele Arrouasse; Sana Aslam; Jean-Philippe Azulay; Jeanette Baker; Ernest Balaguer Martinez; Shadi Barbu; Kara Bardram; Danny Bega; Helena Bejr-Kasem Marco; Isabelle Benatru; Eve Benchetrit; Felix Bernhard; Amir Besharat; Sagari Bette; Amelie Bichon; Andrew Billnitzer; Sophie Blondeau; Thomas Boraud; Freiderike Borngräber; James Boyd; Kathrin Brockmann; Matthew Brodsky; Ethan Brown; Christof Bruecke; Fabienne Calvas; Monica Canelo; Federico Carbone; Claire Carroll; Laura Casado Fernandez; Catherine Cassé-Perrot; Anna Castrioto; Helene Catala; Justine Chan; Samia Cheriet; Anthony Ciabarra; Joseph Classen; Juliana Coleman; Robert Coleman; Yaroslau Compta; Anne-Gaëlle Corbillé; Jean-Christophe Corvol; Mariana Cosgaya; Nabila Dahodwala; Philippe Damier; Elodie David; Thomas Davis; Marissa Dean; Berengere Debilly; Janell DeGiorgio; Andres Deik; Laure Delaby; Marie-Helene Delfini; Pascal Derkinderen; Philipp Derost; Maria de Toledo; Lisa Deuel; Ann Marie Diaz-Hernandez; Cameron Dietiker; Karina Dimenshteyn; Julio Dotor; Franck Durif; Jens Ebentheuer; Karla Maria Eggert; Sara Eichau Madueño; Claudia Eickhoff; Aaron Ellenbogen; Philipp Ellmerer; Ines Esparragosa Vazquez; Alexandre Eusebio; Siobhan Ewert; John Fang; Danielle Feigenbaum; Frederique Fluchere; Alexandra Foubert-Samier; Marie Fournier; Anne Fradet; Valerie Fraix; Samuel Frank; Franca Fries; Monique Galitzky; Marisol Gallardó Pérez; Jose Manuel García Moreno; Carmen Gasca; Thomas Gasser; Joyce Gibbons; Caroline Giordana; Alicia Gonzalez Martinez; Ira Goodman; Arantza Gorospe; Marie Goubeaud; David Grabli; Mangone Graziella; Stephan Grimaldi; Jeffrey Gross; Raquel Guimaraes-Costa; Andreas Hartmann; Christian Hartmann; Travis Hassell; Robert Hauser; Antonio Hernandez; Jorge Hernandez-Vara; Günter Höglinger; Christian Homedes; Andrea Horta-Barba; Jean-Luc Houeto; Julius Huebl; Jennifer Hui; Stuart Isaacson; Joseph Jankovic; Annette Janzen; Junior Jauregui; Jocelyne Jiao; Maria Jose Marti Domenech; Xavier Joseph; Srinath Kadimi; Pat Kaminski; Silja Kannenberg; Jan Kassubek; Maya Katz; Kevin Klos; Shannon Klos; Christopher Kobet; Jennifer Koebert; Patricia Krause; Andrea Kuehn; Jaime Kulisevsky Bojarsky; Rajeev Kumar; Martin Kunz; Lille Kurvits; Kimberly Kwei; Simon Laganiere; Brice Laurens; Johannes Levin; Oren Levy; Peter LeWitt; Gurutz Linazasoro Cristóbal; Irene Litvan; Karlo Lizarraga; Katherine Longardner; Rocio Lopez; Lydia Lopez Manzanares; Sara Lucas del Pozo; Maria Rosario Luquin Puido; Nijee Luthra; Kelly Lyons; Sylvia Maass; Gerrit Machetanz; Yolanda Macias; David Maltete; Jorge Uriel Manez Miro; Louise-Laure Mariani; Juan Marin; Kathrin Marini; Ana Marques; Gloria Marti; Saul Martinez; Wassilios Meissner; Sara Meoni; Dunia Mon Martinez; Johnson Moon; Elena Moro; Peter Morrison; Christoph Muehlberg; Manpreet Multani; Christine Murphy; Anthony Nicholas; Rajesh Pahwa; Antonio Palasi; Heidi Pape; Neepa Patel; Prity Patel; Marina Peball; Elizabeth Peckham; Terry Peery; Rafael Perez; Jesus Perez; Alisa Petit; Elmar Pinkhardt; Elsa Pomies; Cecile Preterre; Joseph Quinn; Olivier Rascol; Philippe Remy; Irene Richard; Benjamin Roeben; Emily Ruether; Jost-Julian Rumpf; David Russell; Hayet Salhi; Daniela Samaniego-Toro; Alexandra Samier-Foubert; Antonio Sanchez; Emmanuelle Schmitt; Alfons Schnitzler; Oliver Schorr; Julie Schwartzbard; Kerstin Schweyer; Klaus Seppi; Victoria Sergo; Holly Shill; Andrew Siderowf; Umberto Spampinato; Ashok Sriram; Natividad Stover; Caroline Tanner; Arjun Tarakad; Carolyn Taylor; Claire Thalamus; Thomas Toothaker; Nadege Van Blercom; Nora Vanegas-Arrogave; Lydia Vela; Sylvian Vergnet; Tiphaine Vidal; Jonathan Vöglein; Ryan Walsh; Cheryl Waters; Mirko Wegscheider; Endy Weidinger; Caroline Weill; Gregor Wenzel; Tatiana Witjas; Isabel Wurster; Brenton Wright; Milan Zimmermann; Rafael Zuzuarregui; Markus Abt; Atieh Bamdadian; Teresa Barata; Nicholas Barbet; Sara Belli; Frank Boess; Edilio Borroni; Jerome Chague; Valerie Cosson; Christian Czech; Dennis Deptula; Cheikh Diack; Juergen Dukart; Giulia D'Urso; Sebastian Dziadek; Hannah Eddleston; Chris Edgar; Laurent Essioux; Morgan Farell; Rebecca Finch; Waltraud Gruenbauer; Andrea Hahn; Stefan Holiga; Michael Honer; Shirin Jadidi; Kelly Johnson-Wood; Markus Keller; Timothy Kilchenmann; Thomas Kremer; Thomas Kustermann; Claire Landsdall; Michael Lindemann; Florian Lipsmeier; Cecile Luzy; Marianne Manchester; Ferenc Martenyi; Meret Martin-Facklam; Katerina Mironova; Annabelle Monnet; Emma Moore; Daniel K Ness; Markus Niggli; Benedicte Passmard; Agnes Poirier; Megana Prasad; Nathalie Pross; Tiffany Quock; Ellen Rose; Christoph Sarry; Christine Schubert; Dennis Selkoe; Kaycee Sink; Hannah Staunton; Tim Steven; Alexander Strasak; Kirsten Taylor; Radhika Tripuraneni; Dylan Trundell; Lynne Verselis; Ekaterina Volkova-Volkmar; Cornelia Weber; Silke Weber; Wagner Zago
Source
Frontiers in Neurology, Vol 12 (2021)
Subject
Language
English
ISSN
1664-2295
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.