2023 American Academy of Neurology Abstract Website

Objective:

To report findings from a pilot sub-study of the Phase 2b tolebrutinib long-term safety (LTS) study (NCT03889639) that assessed compliance with a wearable ActiGraph device and to describe the Phase 3 validation sub-study design assessing the use of actigraphy in measuring gait changes in participants with progressive multiple sclerosis (PwPMS).

Background:

Gait impairment is a common, clinically relevant issue for MS patients. Traditional disability assessments by Expanded Disability Status Scale [EDSS], Timed 25-Foot Walk are widely used, but more sensitive, objective, and clinically meaningful gait impairment measures are needed.

Design/Methods:

The LTS pilot sub-study assessed compliance with the ActiGraph device (defined as 8/14 compliant days with ≥11h/day of device wear/monitoring period) that monitored gait and activity over 4 one-month monitoring periods. The Phase 3 validation sub-study will recruit ~250 PwPMS from PERSEUS (NCT04458051) and HERCULES (NCT04411641) tolebrutinib trials. Participants will be monitored 14 days/month for ≥12 months. Primary endpoint is correlation of gait measures with standard disability progression assessments. Key gait measures include gait speed, step duration, and step length. Physical activity measures include number of steps and walking episodes. Secondary endpoints are to establish normative values for velocity, stride length, and step duration for subsets of EDSS.

Results:

Compliance in the Actigraphy LTS pilot sub-study was 61%–90% over 4 monitoring periods, with a mean daily wear time ranging from 5.9–14.9h. 79% of participants had a mean daily wear time of >10h. Per literature reports, actigraphy gait measures were correlated with EDSS. Findings from Actigraphy LTS pilot sub-study supported the design of the Phase 3 validation sub-study.

Conclusions:

Actigraphy LTS pilot sub-study showed that participants can use the ActiGraph device with relatively good compliance. This Phase 3 validation sub-study will provide further clinical data on actigraphy as a more sensitive measure to track disability progression in PwPMS.