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 - Borngräber, Freiderike
AU - Boyd, James
N1 - Funding Information:
The authors thank all the subjects who participated in this study. PPMI was a public-private partnership sponsored by the Michael J. Fox Foundation (MJFF) for Parkinson’s Research and is co-funded by MJFF, AbbVie, Allergan, Amathus Therapeutics, Avid Radiopharmaceuticals, Bial Biotech, Biogen Idec, BioLegend, Bristol-Myers Squibb, Calico, Celgene, Denali Therapeutics Inc., 4D Pharma Plc, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., GE Healthcare, Genentech Inc., GlaxoSmithKline, Golub Capital BDC, Handl Therapeutics, Insitro, Janssen Neuroscience, Lundbeck, Merck, Meso Scale, Neurocrine Biosciences, Pfizer, Piramal, Prevail Therapeutics, Sanofi Genzyme, Servier, Takeda, Teva Pharmaceutical Industries Ltd., UCB, Verily Life Sciences, and Voyager Therapeutics. Industry partners contribute to PPMI through financial and in-kind donations and have a lead role in providing feedback on study parameters through the Partners Scientific Advisory Board (PSAB). Through close interaction with the study, the PSAB was positioned to inform the selection and review of potential progression markers that could be used in clinical testing.
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
VL - 12
JO - Frontiers in Neurology
JF - Frontiers in Neurology
SN - 1664-2295
M1 - 705407
ER -