Abstract Details

Title Automated Video-based Characterization of Movement Quality in a Phase III Clinical Trial of Troriluzole in Subjects with Spinocerebellar Ataxia

Topic Movement Disorders

Presentation(s) P6 - Poster Session 6 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-014

Objective

To compare the effects of troriluzole versus placebo on gait quality among subjects with spinocerebellar ataxia (SCA) through video-based assessment of gait dispersion.

Background Traditional methods for assessing disease progression often rely on subjective scales and clinical expertise. This brings challenges for assessing patients with SCA, where changes in mobility can be subtle and varied. We hypothesized that a machine learning analytic system may provide a novel perspective, complementing traditional clinician-rated measures of gait.

Design/Methods

This study analyzed videos from participants with SCA who underwent gait assessment in a phase III double-blind placebo-controlled trial of troriluzole (NCT03701399). Videos were analyzed using a deep neural network architecture that tracked coordinates of key body parts and was used to define interpretable kinematic features of dynamic pose dispersion, through the integrated Pose Dispersion Index (PDI) that tracks symmetry, balance, and stability during normal and tandem walk tasks. The effects of troriluzole on PDI were assessed in mixed linear models using fixed effects, subject-level grouping, and ‘treatment group’-by-‘visit week’ interaction, adjusted for age, sex, baseline f-SARA, and time since diagnosis.

Results From 218 randomized subjects, 67 and 56 subjects had interpretable videos of a tandem and normal walk attempt, respectively. Over 48-weeks, individuals assigned to troriluzole exhibited significant improvement in tandem walk PDI versus placebo (adj. interaction coefficient: 0.58 (95% CI: 0.14 to 1.03)). A similar but not statistically significant trend was observed in the normal walk assessment (coef. 1.20 (95%CI: -1.07 to 3.46)). Lower baseline PDI during normal walk was associated with a higher risk of subsequent falls (adj. Poisson coef. -0.36 [95% CI -0.70 to -0.01]).

Conclusions

Machine learning applied to video-captured gait parameters introduces a quantitative approach to motor assessment in cerebellar ataxia. The metrics captured in the PDI show that troriluzole-treated individuals with SCA demonstrated improvement in cerebellar motor function compared to controls.

Authors/Disclosures
Melissa Beiner PRESENTER	Melissa Beiner has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Melissa Beiner has stock in Biohaven Pharmaceuticals.
Evangelos Oikonomou (Yale School of Medicine)	No disclosure on file
Gilbert J. L'Italien	Gilbert J. L'Italien has received personal compensation for serving as an employee of Biohaven Pharmaceuticals. Gilbert J. L'Italien has stock in biohaven pharmaceuticals.
Rohan Khera (Yale University)	No disclosure on file
Michele Potashman, PhD (Biohaven)	Dr. Potashman has received personal compensation for serving as an employee of Biohaven Pharmaceuticals.
Jeremy D. Schmahmann, MD, FAAN (Massachusettes General Hospital)	Dr. Schmahmann has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care.
Susan L. Perlman, MD (UCLA)	Dr. Perlman has nothing to disclose.
Vladimir Coric	Vladimir Coric has received personal compensation for serving as an employee of Biohaven. Vladimir Coric has received personal compensation in the range of $1,000,000+ for serving as an officer or member of the Board of Directors for Bioahven. Vladimir Coric has stock in Biohaven. Vladimir Coric has received intellectual property interests from a discovery or technology relating to health care.

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