North Star (NSAA and NSAD) Functional Assessments in Individuals with Becker Muscular Dystrophy

Topic:

Clinical Trials

Poster Number: M147

Author(s):

James MacDougall, PhD, Edgewise Therapeutics, Meredith James, PT, The John Walton Muscular Dystrophy Research Centre, Craig McDonald, MD, UC Davis Health, Han Phan, MD, Rare Disease Research, John Vissing, MD, DMSci, Rigshospitalet, University of Copenhagen, Michelle Eagle, PT, PhD, ATOM International, Linda Lowes, PT, PhD, Nationwide Children's Hospital, Lindsay Alfano, DPT, Nationwide Children's Hospital, Joanne Donovan, PhD, MD, Edgewise Therapeutics

Background
Becker muscular dystrophy (Becker) is characterized by contraction-induced injury causing muscle replacement with fat and fibrosis, with consequent loss of ambulatory functions. The North Star Ambulatory Assessment (NSAA) and North Star Assessment for Limb-Girdle type muscular dystrophies (NSAD) are multi-item scales utilized in natural history studies to longitudinally assess functional measures in Becker.

Objectives
To understand reproducibility of NSAA and NSAD in Becker using repeated pre-treatment assessments in clinical trials of EDG-5506, an orally administered fast skeletal muscle myosin inhibitor designed to prevent contraction-induced muscle damage (NCT05160415/05291091), and to examine patterns of compensation/loss of individual functions over a range of baseline NSAA/NSAD scores.

Results
This analysis included ambulatory participants (ages 16-50) with Becker assessed with NSAA and NSAD at visits up to 3 weeks apart (n=82, with 65 at both visits), prior to initiating study drug treatment. Assessments were conducted by clinical evaluators with standardized training. Mean score change of repeat assessments was -0.1 (SD1.6) for NSAA, and -0.6 (SD2.1) for NSAD, with intraclass correlations of 0.984 and 0.986, respectively. NSAA and NSAD were highly correlated (r=0.985 and 0.988, respectively), while score of items in the NSAD not included in the NSAA had an intraclass correlation of 0.964 (correlation=0.967). With decreasing NSAA/NSAD scores, activities conducted either with compensation or loss depict a picture of sequential loss of abilities that give insight into impact of disease progression.

Conclusions
In clinical trials in Becker NSAA and NSAD are highly reproducible functional assessments directly related to activities of daily living. Certain measures appear to be affected earlier (stand from chair), i.e., at higher NSAA scores, or later (lift head) than has been observed in Duchenne. This information is helpful in interpreting the clinical meaningfulness of changes in these clinical outcome measures in clinical trials in Becker, a serious disease without approved therapies.