Objective: To evaluate a novel quantitative measure of Parkinson’s disease (PD) severity and progression in a Phase II clinical trial.

Background: Cinpanemab, a monoclonal antibody, was being investigated as a therapeutic for Parkinson’s disease in a Phase II, double blind, placebo-controlled clinical trial SPARK (NCT03318523). The SPARK study included a novel digital component called the quantitative movement assessment (QMA) based on wearable inertial measurement unit (IMU) sensors. A digital composite score was obtained from the sensor data acquired during the QMA as an exploratory endpoint. After a 52-week placebo-controlled treatment phase, participants in the placebo group in year 1 were randomized to one of the active-treatment arms. After 18 months, the change-from-baseline of the digital composite score was evaluated.

Method: A wearable sensor-based movement monitoring system (Mobility Lab, APDM Inc.) was used to obtain data from the participants during a clinic visit (Q8wk). Data were acquired from 5 synchronized sensors (L5 lumbar, bilateral wrist, and top of each foot) while the participants completed the QMA — a series of actions involving repeated arm and leg movements, walking, sitting, and standing still. Signal features were extracted from data derived from the sensors, and were chosen to reflect phenomena of motion that comprise the clinical definition of PD cardinal signs. Features were converted into z-scores based on their distribution at the baseline visit, and summed to generate a QMA digital composite score. A mixed model for repeated measures (MMRM) was used to model the mean change of the digital composite score from baseline over time for the various treatment groups.

Results: The QMA digital composite score is based on sensor-derived features from the QMA that capture bradykinesia (83%), tremor (14%), and postural instability (3%). Analysis of the SPARK data demonstrated that the QMA score tracked with the MDS-UPDRS part III score and was sensitive to detect PD longitudinal progression, but did not show any significant difference between the placebo and the active-treatment groups at year 1.

Conclusion: A novel, digital composite score derived from the QMA sensor data provided an objective measure of increasing PD clinical severity over the course of the study. This approach has potential utility as an endpoint in future clinical trials for PD.

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/measuring-progression-of-parkinsons-disease-cardinal-signs-in-the-phase-2-spark-study/