AUTHOR=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 , PASADENA Investigators , Prasinezumab Study Group , 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 , Toledo Maria de , 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 , Eusebio Alexandre , Ewert Siobhan , Fang John , Feigenbaum Danielle , Fluchere Frederique , Foubert-Samier Alexandra , Fournier Marie , Fradet Anne , Fraix Valerie , Frank Samuel , Fries Franca , Galitzky Monique , Pérez Marisol Gallardó , Moreno Jose Manuel García , Gasca Carmen , Gasser Thomas , Gibbons Joyce , Giordana Caroline , Martinez Alicia Gonzalez , Goodman Ira , Gorospe Arantza , Goubeaud Marie , Grabli David , Graziella Mangone , Grimaldi Stephan , Gross Jeffrey , Guimaraes-Costa Raquel , Hartmann Andreas , Hartmann Christian , Hassell Travis , Hauser Robert , Hernandez Antonio , Hernandez-Vara Jorge , Höglinger Günter , Homedes Christian , Horta-Barba Andrea , Houeto Jean-Luc , Huebl Julius , Hui Jennifer , Isaacson Stuart , Jankovic Joseph , Janzen Annette , Jauregui Junior , Jiao Jocelyne , Domenech Maria Jose Marti , Joseph Xavier , Kadimi Srinath , Kaminski Pat , Kannenberg Silja , Kassubek Jan , Katz Maya , Klos Kevin , Klos Shannon , Kobet Christopher , Koebert Jennifer , Krause Patricia , Kuehn Andrea , Bojarsky Jaime Kulisevsky , Kumar Rajeev , Kunz Martin , Kurvits Lille , Kwei Kimberly , Laganiere Simon , Laurens Brice , Levin Johannes , Levy Oren , LeWitt Peter , Cristóbal Gurutz Linazasoro , Litvan Irene , Lizarraga Karlo , Longardner Katherine , Lopez Rocio , Manzanares Lydia Lopez , Pozo Sara Lucas del , Puido Maria Rosario Luquin , Luthra Nijee , Lyons Kelly , Maass Sylvia , Machetanz Gerrit , Macias Yolanda , Maltete David , Miro Jorge Uriel Manez , Mariani Louise-Laure , Marin Juan , Marini Kathrin , Marques Ana , Marti Gloria , Domenech Maria Jose Marti , Martinez Saul , Meissner Wassilios , Meoni Sara , Mollenhauer Brit , Martinez Dunia Mon , Moon Johnson , Moro Elena , Morrison Peter , Muehlberg Christoph , Multani Manpreet , Murphy Christine , Nicholas Anthony , Pahwa Rajesh , Palasi Antonio , Pape Heidi , Patel Neepa , Patel Prity , Peball Marina , Peckham Elizabeth , Peery Terry , Perez Rafael , Perez Jesus , Petit Alisa , Pinkhardt Elmar , Poewe Werner , Pomies Elsa , Preterre Cecile , Quinn Joseph , Rascol Olivier , Remy Philippe , Richard Irene , Roeben Benjamin , Ruether Emily , Rumpf Jost-Julian , Russell David , Salhi Hayet , Samaniego-Toro Daniela , Samier-Foubert Alexandra , Sanchez Antonio , Schmitt Emmanuelle , Schnitzler Alfons , Schorr Oliver , Schwartzbard Julie , Schweyer Kerstin , Seppi Klaus , Sergo Victoria , Shill Holly , Siderowf Andrew , Simuni Tanya , Spampinato Umberto , Sriram Ashok , Stover Natividad , Tanner Caroline , Tarakad Arjun , Taylor Carolyn , Thalamus Claire , Toothaker Thomas , Blercom Nadege Van , Vanegas-Arrogave Nora , Vela Lydia , Vergnet Sylvian , Vidal Tiphaine , Vöglein Jonathan , Walsh Ryan , Waters Cheryl , Wegscheider Mirko , Weidinger Endy , Weill Caroline , Wenzel Gregor , Witjas Tatiana , Wurster Isabel , Wright Brenton , Zimmermann Milan , Zuzuarregui Rafael , Abt Markus , Bamdadian Atieh , Barata Teresa , Barbet Nicholas , Belli Sara , Boess Frank , Bonni Azad , Borroni Edilio , Boulay Anne , Britschgi Markus , Chague Jerome , Cosson Valerie , Czech Christian , Deptula Dennis , Diack Cheikh , Doody Rachelle , Dukart Juergen , D'Urso Giulia , Dziadek Sebastian , Eddleston Hannah , Edgar Chris , Essioux Laurent , Farell Morgan , Finch Rebecca , Fontoura Paulo , Gruenbauer Waltraud , Hahn Andrea , Holiga Stefan , Honer Michael , Jadidi Shirin , Johnson-Wood Kelly , Keller Markus , Kilchenmann Timothy , Koller Martin , Kremer Thomas , Kustermann Thomas , Landsdall Claire , Lindemann Michael , Lipsmeier Florian , Luzy Cecile , Manchester Marianne , Marchesi Maddalena , Martenyi Ferenc , Martin-Facklam Meret , Mironova Katerina , Monnet Annabelle , Moore Emma , Ness Daniel K , Niggli Markus , Nikolcheva Tania , Ostrowitzki Susanne , Pagano Gennaro , Passmard Benedicte , Poirier Agnes , Post Anke , Prasad Megana , Pross Nathalie , Quock Tiffany , Ricci Benedicte , Rose Ellen , Sarry Christoph , Schubert Christine , Selkoe Dennis , Sevigny Jeff , Sink Kaycee , Staunton Hannah , Steven Tim , Strasak Alexander , Svoboda Hanno , Taylor Kirsten , Tripuraneni Radhika , Trundell Dylan , Umbricht Daniel , Verselis Lynne , Vogt Annamarie , Volkova-Volkmar Ekaterina , Weber Cornelia , Weber Silke , Zago Wagner
TITLE=A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
JOURNAL=Frontiers in Neurology
VOLUME=12
YEAR=2021
URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.705407
DOI=10.3389/fneur.2021.705407
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.