Exploratory digital outcome measures of motor sign progression in Parkinson's disease patients treated with prasinezumab

Abstract

Digital health technology (DHT) tools for Parkinson's disease (PD) e.g., smartphones and wearables were used for remote and frequent measurement of motor signs in the phase 2 PASADENA study of the anti-alpha-synuclein monoclonal antibody prasinezumab. 316 early-stage PD participants were randomized to placebo, 1500 mg, or 4500 mg prasinezumab for 52 weeks; placebo participants were re-randomized to prasinezumab for the ensuing 52 weeks. Patients performed daily smartphone motor "active tests", and were passively monitored by smartphone/smartwatch throughout the day over 2 y. Change from baseline analyses censored data at dopaminergic treatment start. Bilateral speeded tapping variability and hand-turning, U-turn speed, passively monitored hand movement power, and summary Simple Sum scores progressed numerically less in prasinezumab-treated vs placebo at week 52. All findings except hand-turning persisted at week 104. DHT sensor-based outcome measures may contribute to quantifying disease progression in clinical research of early-stage, dopaminergic treatment-naïve PD. Clinical Trial Registry Name: ClinicalTrials.gov; Clinical Trial Registry ID: NCT03100149; registered 2017-03-29.

Fig. 1. Adherence to remote DHT monitoring.

Mean (error shading represents 95% confidence intervals) adherence to daily (a) active testing (AT) with the smartphone and (b) passive monitoring (PM) with the smartwatch and smartphone Roche PD Mobile Application v2 during Parts 1 (i.e., weeks 0–52 since randomization) and 2 (i.e., weeks 52–104 since randomization) of the PASADENA study.

Fig. 2. Progression of individual sensor outcome measures in individuals with PD on placebo (black) and prasinezumab (blue).

Progression of sensor features which surpassed the exploratory threshold for a group effect in PASADENA Part 1 is shown: (a) passively monitored gesture power during non-gait segments; (b) hand-turning, least affected side; (c) U-turn test; (d) speeded tapping, most affected and (e) least affected sides; (f) hand-turning, most affected side. Data from both the RCT PASADENA Part 1 (first 52 weeks; placebo group data plotted in black, pooled prasinezumab group data plotted in blue) and PASADENA Part 2 (second 52 weeks) in which all participants received prasinezumab (all data plotted in blue) are shown. Only data collected prior to the start of dopaminergic therapy are analyzed and plotted. Statistics are reported beneath each figure: estimates from the LMEs are coefficients of the fortnight-by-treatment arm interaction term (difference in slopes between the two arms), while estimates from MMRM are reported as contrasts between the pooled prasinezumab and placebo arms at the last study fortnight in the analysis.

Fig. 3. Progression of summary Simple Sum Score sensor outcome measure and MDS-UPDRS Part III in individuals with PD on placebo (black) and prasinezumab (blue).

a Progression on motor signs in the pooled early- and delayed-start prasinezumab groups as measured by Simple Sum v1.2 score (results from the linear mixed effects models (LMEs) are reported) and (b) the MDS-UPDRS Part III. Only data collected prior to the start of dopaminergic therapy are analyzed and plotted. For both metrics, higher scores indicate more severe motor signs. b is adapted from ref. , Copyright ©2022 Massachusetts Medical Society. Reprinted with permission.

Fig. 4. Roche PD Mobile Application v2 testing suite and schedule.

Patients used provisioned study smartphones to perform daily “active tests”, circa half on alternating days, and motor behavior in daily life was “passively monitored” via the smartphone worn in a running belt or pocket and a provisioned study smartwatch.