Frontiers in Neurology (Oct 2021)

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

  • Gennaro Pagano,
  • Frank G. Boess,
  • Kirsten I. Taylor,
  • Kirsten I. Taylor,
  • Benedicte Ricci,
  • Brit Mollenhauer,
  • 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,
  • Maria Jose Marti Domenech,
  • Saul Martinez,
  • Wassilios Meissner,
  • Sara Meoni,
  • Brit Mollenhauer,
  • 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,
  • Werner Poewe,
  • 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,
  • Tanya Simuni,
  • 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,
  • Azad Bonni,
  • Edilio Borroni,
  • Anne Boulay,
  • Markus Britschgi,
  • Jerome Chague,
  • Valerie Cosson,
  • Christian Czech,
  • Dennis Deptula,
  • Cheikh Diack,
  • Rachelle Doody,
  • Juergen Dukart,
  • Giulia D'Urso,
  • Sebastian Dziadek,
  • Hannah Eddleston,
  • Chris Edgar,
  • Laurent Essioux,
  • Morgan Farell,
  • Rebecca Finch,
  • Paulo Fontoura,
  • Waltraud Gruenbauer,
  • Andrea Hahn,
  • Stefan Holiga,
  • Michael Honer,
  • Shirin Jadidi,
  • Kelly Johnson-Wood,
  • Markus Keller,
  • Timothy Kilchenmann,
  • Martin Koller,
  • Thomas Kremer,
  • Thomas Kustermann,
  • Claire Landsdall,
  • Michael Lindemann,
  • Florian Lipsmeier,
  • Cecile Luzy,
  • Marianne Manchester,
  • Maddalena Marchesi,
  • Ferenc Martenyi,
  • Meret Martin-Facklam,
  • Katerina Mironova,
  • Annabelle Monnet,
  • Emma Moore,
  • Daniel K Ness,
  • Markus Niggli,
  • Tania Nikolcheva,
  • Susanne Ostrowitzki,
  • Gennaro Pagano,
  • Benedicte Passmard,
  • Agnes Poirier,
  • Anke Post,
  • Megana Prasad,
  • Nathalie Pross,
  • Tiffany Quock,
  • Benedicte Ricci,
  • Ellen Rose,
  • Christoph Sarry,
  • Christine Schubert,
  • Dennis Selkoe,
  • Jeff Sevigny,
  • Kaycee Sink,
  • Hannah Staunton,
  • Tim Steven,
  • Alexander Strasak,
  • Hanno Svoboda,
  • Kirsten Taylor,
  • Radhika Tripuraneni,
  • Dylan Trundell,
  • Daniel Umbricht,
  • Lynne Verselis,
  • Annamarie Vogt,
  • Ekaterina Volkova-Volkmar,
  • Cornelia Weber,
  • Silke Weber,
  • Wagner Zago

DOI
https://doi.org/10.3389/fneur.2021.705407
Journal volume & issue
Vol. 12

Abstract

Read online

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.

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