Category: MSA, PSP, CBS: Clinical Trials
Objective: To compare the properties of PSPRS-28, mPSPRS-15, and the rPSPRS-10 and assess their utility as a primary endpoint in PSP trials.
Background: Progressive supranuclear palsy (PSP), a rare and fatal neurodegenerative disease associated with 4-R tauopathy, is characterized by progressive impairment in physical, behavioral and cognitive function. The Progressive Supranuclear Palsy Rating Scale (PSPRS), a 28-item clinician-reported scale, is the most established clinical outcome assessment used as a primary endpoint in PSP trials. However, some items in the PSPRS may lack relevance to daily activities1 and fail to address core aspects of o the disease or show limited responsiveness to changes withing a typical 12-month trial period. To address these challenges, modified versions of the PSPRS have been developed guided by feedback from United States Food and Drug Administration (FDA): the mPSPRS-151 (15 items), 10 item version with no rescoring (PSPRS-10)2,3, and 10 item version with rescoring (rPSPRS-10)2,3 are examples of this collaboration with FDA. The rPSPRS-10 assesses history, bulbar, and gait performances, while the mPSPRS-15 includes the same 10 items as the rPSPRS-10 along with four oculomotor items and limb dystonia.
Method: Data from the PASSPORT study (NCT03068468), a Phase 2 clinical trial investigating the efficacy, safety, and tolerability of gosuranemab in PSP, were analyzed. Longitudinal data from baseline to week 52 were assessed using mixed-model repeated measures (MMRM) to compare the sensitivity of the PSPRS-28, mPSPRS-15, and rPSPRS-10 in measuring the disease progression of participants with PSP.
Results: Longitudinal analyses from baseline to week 52 in the PASSPORT study using MMRM indicated that rPSPRS-10 and mPSPRS-15 were more sensitive at detecting meaningful changes in disease progression than PSPRS-28.
Conclusion: Evaluation of PSPRS variants and detection of a statistically significant treatment effect are crucial for successful PSP trials. The modified PSPRS scales show enhanced sensitivity for evaluating clinical progression of PSP in trials, highlighting their potential use as primary endpoints. These findings have significant implications for the design of future PSP trials, particularly in improving the detection of treatment effects.
References: 1. Dam T, Yang L, Gillis C, Li Y, O’Gorman J, Kolb B, Boxer AL, Golbe L, Budd Haeberlein S; AL-108-231, PROSPERA, and 4RTNI investigators. A 15-Item modification of the PSP rating scale to improve clinical meaningfulness and statistical performance. Nat Commun. 2025 Jan 6;16(1):414. doi: 10.1038/s41467-024-55442-0.
2. Gewily M, Plan EL, Yousefi E, König F, Posch M, Hopfner F, Höglinger G, Karlsson MO. Quantitative Comparisons of Progressive Supranuclear Palsy Rating Scale Versions Using Item Response Theory. Mov Disord. 2024 Dec;39(12):2181-2189. doi: 10.1002/mds.30001.
3. Yousefi E, Gewily M, König F, Höglinger G, Hopfner F, Karlsson MO, Ristl R, Zehetmayer S, Posch M. Efficiency of multivariate tests in trials in progressive supranuclear palsy. Sci Rep. 2024 Oct 26;14(1):25581. doi: 10.1038/s41598-024-76668-4.
To cite this abstract in AMA style:
F. Nery, T. Nevmyrych, J. Murphy, S. Wu, Y. Zabar, A. Gafson, S. Bullain, J. O’Gorman. Utilizing the 15-item modification of the PSPRS rating scale (mPSPRS-15) as the primary endpoint for future clinical trials in progressive supranuclear palsy [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/utilizing-the-15-item-modification-of-the-psprs-rating-scale-mpsprs-15-as-the-primary-endpoint-for-future-clinical-trials-in-progressive-supranuclear-palsy/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/utilizing-the-15-item-modification-of-the-psprs-rating-scale-mpsprs-15-as-the-primary-endpoint-for-future-clinical-trials-in-progressive-supranuclear-palsy/