- Main
A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
- 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;
- 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;
- 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;
- del Pozo, Sara Lucas;
- 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;
- Van Blercom, Nadege;
- 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;
- 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
- et al.
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.
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