Objective: To determine what percentage of subjects with early Parkinson’s disease demonstrated no measurable worsening of MDS-UPDRS motor scores over 52 weeks in a Phase 2 clinical trial.

Background: Parkinson’s disease (PD) affects more than 6 million people globally. PD symptoms progressively worsen over time at a rate that varies across individuals. In clinical trials that aim to evaluate treatment-related slowing of disease progression, it is important that the primary outcome measure detects worsening in subjects not receiving an effective treatment. PD severity in clinical trials is most often measured using the MDS-UPDRS score, and here we analyzed MDS-UPDRS scores from subjects in a Phase 2 clinical trial to determine the fraction of participants for whom MDS-UPDRS showed no progression over 52 weeks.

Method: MDS-UPDRS motor scores (combined II+III score) were analyzed from participants in the SPARK trial [1] who had at least 4 MDS-UPDRS assessments during their first study year excluding visits occurring after initiation of PD symptomatic medication. The percentage of subjects who did not measurably worsen from baseline to week 52 according to MDS-UPDRS II+III was estimated using a two-stage method: (1) change scores were predicted using linear regression; (2) an empirical Bayes deconvolution method was applied to the predicted change to remove prediction error [2].

Results: 330 PD participants were included in this analysis, with mean age 60 years, 31% female, mean baseline MDS-UPDR II+III score of 27.4, and mean baseline SBR (DaT SPECT striatal binding ratio) of 1.35. The cohort consisted of 71% Tremor Dominant, 22% PIGD, and 7% indeterminate PD subtypes. The percentage of subjects with no measurable worsening is estimated to be 29.4% (95% CI, 24.5% – 34.3%) based on the observed change in MDS-UPDRS II+III score from baseline to week 52. When applying the linear regression models and the empirical Bayes deconvolution method, the estimated percentage with no measurable worsening is 34.4% (95% CI, 23.3% – 45.5%).

Conclusion: In this multi-center, phase II, interventional trial, a substantial fraction (34.4%) of subjects showed no measurable worsening over 52 weeks according to the MDS-UPDRS combined motor score. This highlights the need for more sensitive measures of PD progression to enable development of new treatments.

References: [1] Lang AE et al., (2022). NEJM 387: 408-420.
[2] Efron B (2016). Biometrika 103: 1-20.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/estimating-the-proportion-of-parkinsons-disease-clinical-trial-subjects-who-showed-no-measurable-mds-updrs-motor-score-progression-over-1-year/