Validity of remote evaluation of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy

Topic:

Clinical Management

Poster Number: 12

Author(s):

Linda Lowes, PhD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Lindsay Alfano, DPT, PCS, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Megan Iammarino, DPT, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Natalie Reash, DPT, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Kathryn Giblin, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Larry Hu, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Lixi Yu, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Shufang Wang, Sarepta Therapeutics, Inc., Cambridge, MA, USA, Jerry Mendell, MD, Nationwide Children's Hospital

Background: Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy developed for targeted skeletal and cardiac muscle expression of micro-dystrophin—a shortened, functional dystrophin protein. In ongoing delandistrogene moxeparvovec Studies 101 and 102, remote functional assessments were initiated during the COVID-19 pandemic, in accordance with US Food and Drug Administration guidance.

Objectives: To evaluate the reliability of remote assessment of functional measures versus in-person testing, we assessed the reproducibility of remote North Star Ambulatory Assessment (NSAA), 10-Meter Walk/Run (10MWR), and Time to Rise scores against in-person scores using pre-specified statistical analyses—including Intraclass Correlation Coefficient (ICC), Pearson, Spearman, and Bland-Altman analyses.

Results: Preliminary results from eight patients with Duchenne muscular dystrophy (DMD), who completed an in-clinic assessment within 2 weeks of a remote assessment in Part 1 of Study 102, found strong correlations between remote and in-person NSAA scores (ICC=0.97 [95% CI 0.87–0.99]; Pearson=0.98 [95% CI 0.88–1.00]; Spearman=0.93 [95% CI 0.66–0.99]). Analysis of all the eight patients from Part 1 of Study 102 showed no statistical or clinical differences in NSAA scores attained remotely versus in person. Results from additional patients in Studies 101 and 102 (Parts 1 and 2), including correlations between remote and in-person scores on the 10MWR and Time to Rise, will also be presented.

Conclusions: These findings suggest that remote functional assessment of patients with DMD is not statistically different from assessment conducted in person and has comparable clinical meaningfulness, validating its use in clinical trials and specifically in Studies 101 and 102 of delandistrogene moxeparvovec. Given the significant burden that treatment and monitoring places on patients with DMD and their caregivers, remote assessment may be beneficial in future research, clinical trials, and clinical settings.

This study is funded by Sarepta Therapeutics, Inc.