Journal Article

DZNE-2025-00228

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Combined Assessment of Function and Survival to Demonstrate the Effect of Treatment on Progressive Supranuclear Palsy.

Germani, M. ; Rebollo Mesa, I. ; Buchanan, T. J. ; De Bruyn, S. ; Gasalla, T. ; Van Tricht, H. L. G. ; Ewen, C. ; Golbe, L. I. ; Boxer, A. ; Höglinger, G. (Last author)DZNE*

2025
Wiley New York, NY

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Please use a persistent id in citations: doi:10.1002/mds.30027

Abstract: Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease-modifying treatments. Recent trials of potential therapies had durations of 12 months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error. Selecting efficacy measures more sensitive to disease modification may facilitate identification of treatment effect.The objective of this study was to evaluate the simulated phase 3 PSP trial assessing the effect of disease-modifying intervention on a novel combined primary endpoint comprising function (PSP Rating Scale) and survival, the Combined Assessment of Function and Survival (CAFS), and to determine operating characteristics of the CAFS.To simulate PSP progression in the trial population, we developed models of PSP Rating Scale and survival using data from published clinical studies. These models were used to define operating characteristics of the CAFS for use in a phase 3 trial.The sample size determined (N = 384; 1:1 randomization) would provide >80% power to detect significant treatment effects on the CAFS compared with placebo. The CAFS provides good operating characteristics and increased power to detect moderate treatment effects on the PSP Rating Scale. We propose a trial design allowing potential detection of treatment effects at a preplanned interim analysis after participants complete 12 months of treatment, with assessment of effects of treatment (≤24 months) on survival.Use of the CAFS could provide a comprehensive and robust estimate of the clinical benefit of future therapies. © 2024 UCB. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keyword(s): Supranuclear Palsy, Progressive: drug therapy (MeSH) ; Supranuclear Palsy, Progressive: physiopathology (MeSH) ; Humans (MeSH) ; Disease Progression (MeSH) ; Male (MeSH) ; Female (MeSH) ; Treatment Outcome (MeSH) ; Severity of Illness Index (MeSH) ; Aged (MeSH) ; clinical rating scale ; item response theory ; joint rank test ; neurodegenerative disease ; progressive supranuclear palsy

Note: This research was funded by UCB. G.H. was supported by the European Joint Programme on Rare Diseases (Improve-PSP) and the Deutsche Forschungsgemeinschaft DFG, (German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy ID 390857198).

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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