TY - JOUR
T1 - A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA)
T2 - Rationale, Design, and Baseline Data
AU - PASADENA Investigators
AU - Prasinezumab Study Group
AU - Pagano, Gennaro
AU - Boess, Frank G.
AU - Taylor, Kirsten I.
AU - Ricci, Benedicte
AU - Mollenhauer, Brit
AU - Poewe, Werner
AU - Boulay, Anne
AU - Anzures-Cabrera, Judith
AU - Vogt, Annamarie
AU - Marchesi, Maddalena
AU - Post, Anke
AU - Nikolcheva, Tania
AU - Kinney, Gene G.
AU - Zago, Wagner M.
AU - Ness, Daniel K.
AU - Svoboda, Hanno
AU - Britschgi, Markus
AU - Ostrowitzki, Susanne
AU - Simuni, Tanya
AU - Marek, Kenneth
AU - Koller, Martin
AU - Sevigny, Jeff
AU - Doody, Rachelle
AU - Fontoura, Paulo
AU - Umbricht, Daniel
AU - Bonni, Azad
AU - Altendorf, Claudia
AU - Anandan, Chareyna
AU - Andrews, Giulia
AU - Ansquer, Solène
AU - Arrouasse, Raphaele
AU - Aslam, Sana
AU - Azulay, Jean Philippe
AU - Baker, Jeanette
AU - Martinez, Ernest Balaguer
AU - Barbu, Shadi
AU - Bardram, Kara
AU - Bega, Danny
AU - Bejr-Kasem Marco, Helena
AU - Benatru, Isabelle
AU - Benchetrit, Eve
AU - Bernhard, Felix
AU - Besharat, Amir
AU - Bette, Sagari
AU - Bichon, Amelie
AU - Billnitzer, Andrew
AU - Blondeau, Sophie
AU - Boraud, Thomas
AU - Brodsky, Matthew
AU - Quinn, Joseph
N1 - Publisher Copyright:
© Copyright © 2021 Pagano, Boess, Taylor, Ricci, Mollenhauer, Poewe, Boulay, Anzures-Cabrera, Vogt, Marchesi, Post, Nikolcheva, Kinney, Zago, Ness, Svoboda, Britschgi, Ostrowitzki, Simuni, Marek, Koller, Sevigny, Doody, Fontoura, Umbricht, Bonni and PASADENA Investigators and Prasinezumab Study Group.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - MDS-UPDRS = Movement Disorder Society—Unified Parkinson's Disease Rating Scale
KW - Parkinson's disease
KW - Phase II clinical trial
KW - alpha-synuclein (α-syn)
KW - disease modification treatments
KW - disease progression
KW - monoclonal antibodies
KW - prasinezumab
UR - http://www.scopus.com/inward/record.url?scp=85117211748&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117211748&partnerID=8YFLogxK
U2 - 10.3389/fneur.2021.705407
DO - 10.3389/fneur.2021.705407
M3 - Article
AN - SCOPUS:85117211748
SN - 1664-2295
VL - 12
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 705407
ER -