A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data
Por:
Pagano, G, Boess, FG, Taylor, KI, Ricci, B, Mollenhauer, B, Poewe, W, Boulay, A, Anzures-Cabrera, J, Vogt, A, Marchesi, M, Post, A, Nikolcheva, T, Kinney, GG, Zago, WM, Ness, DK, Svoboda, H, Britschgi, M, Ostrowitzki, S, Simuni, T, Marek, K, Koller, M, Sevigny, J, Doody, R, Fontoura, P, Umbricht, D, Bonni, A, PASADENA Investigators, Bejr-Kasem, H, Bojarsky J.K., Prasinezumab Study Grp
Publicada:
1 oct 2021
Resumen:
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 naive 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-naive 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-naive 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 naive 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 naive).
Conclusions: The PASADENA study population is suitable to investigate the potential of prasinezumab to slow disease progression in individuals with early PD.
Filiaciones:
Pagano, G:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Boess, FG:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Taylor, KI:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Univ Basel, Fac Psychol, Basel, Switzerland
Ricci, B:
F Hoffmann La Roche Ltd, Roche Innovat Ctr, Pharmaceut Sci, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Mollenhauer, B:
Paracelsus Elena Klin, Kassel, Germany
Univ Med Ctr Gottingen, Dept Neurol, Gottingen, Germany
Poewe, W:
Innsbruck Med Univ, Dept Neurol, Innsbruck, Austria
Boulay, A:
Idorisa Pharmaceut Ltd, Allschwil, Switzerland
Anzures-Cabrera, J:
Roche Prod Ltd, Welwyn Garden City, Herts, England
Vogt, A:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Marchesi, M:
F Hoffmann La Roche Ltd, Roche Innovat Ctr, Pharmaceut Sci, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Post, A:
Feetme SAS, Paris, France
Nikolcheva, T:
F Hoffmann La Roche Ltd, Basel, Switzerland
Kinney, GG:
Prothena Biosci Inc, San Francisco, CA USA
Zago, WM:
Prothena Biosci Inc, San Francisco, CA USA
Ness, DK:
Prothena Biosci Inc, San Francisco, CA USA
Svoboda, H:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Britschgi, M:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Ostrowitzki, S:
F Hoffmann La Roche Ltd, Basel, Switzerland
Simuni, T:
Northwestern Univ, Feinberg Sch Med, Dept Neurol, Chicago, IL 60611 USA
Marek, K:
Inst Neurodegenerat Disorders, New Haven, CT USA
Koller, M:
Prothena Biosci Inc, San Francisco, CA USA
Sevigny, J:
Prevail Therapeut, New York, NY USA
Doody, R:
F Hoffmann La Roche Ltd, Basel, Switzerland
Fontoura, P:
F Hoffmann La Roche Ltd, Basel, Switzerland
Umbricht, D:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Bonni, A:
F Hoffmann La Roche Ltd, Neurosci & Rare Dis Discovery & Translat Area, Roche Innovat Ctr, Roche Pharma Res & Early Dev pRED, Basel, Switzerland
Bejr-Kasem, H:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
Bojarsky J.K.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
gold, Green Published, Green Submitted
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