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=Volume 12 - 2021

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=Currently available treatments for Parkinson’s disease (PD) do not slow clinical progression nor target alpha-synuclein, the main pathology associated with the disease. 

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. Study rationale, design, and baseline characteristics of enrolled subjects are presented here.

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 (1500 mg or 4500 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. 

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 Total score [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 Total score [SD]; 31.41 [12.78], 32.63 [13.04], respectively) to the PPMI cohort (all treatment naïve). 

The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.