Identifying factors associated with variable rates of change in clinical outcomes is necessary to inform clinical trial design, especially when placebo controls are limited or infeasible. We assessed predictors of 12-month changes in the North Star Assessment for Dysferlinopathy (NSAD) total score using natural history data from 164 LGMD patients in study MLB-01-001 (NCT04202627); with genetically confirmed mutation in the Fukutin-related protein (FKRP) gene (LGMD2i). The NSAD is a 29-item clinician-reported measure of motor function with total scores ranging from 54 (best function) to 0 (worst function). At baseline, the mean (standard deviation [SD]) NSAD total score was 27.5 (16.7); 89.0% could stand, 86.0% could roll from supine to prone, 81.7% could walk and 45.7% could rise from the floor. The median age was 35.5 (range 7-64) years and 54.3% were female. The most common mutations were FKRP (47.6%) and CAPN3 (23.2%). The mean 12-month change in NSAD total score was -1.7 (3.6) units. Significant predictors in a multivariable model were age and ability to rise from the floor. Gender, race and mutation type did not add significant prognostic value. Among patients younger than 35 years (n=76), the mean (SD) 12-month NSAD change was -2.3 (3.9) units, versus -1.1 (3.3) for those older (n=88). Among patients able to rise independently from the floor with an NSAD item score of 2 (no Gower’s maneuver; n=16) or 1 (with Gower’s; n=59), the mean (SD) 12-month NSAD changes were -0.3 (2.7) and -2.6 (4.7), respectively, versus -1.3 (2.7) among those unable (n=89). Important predictors of 12-month change in NSAD scores were identified and indicate faster declines among patients who are younger or require a Gower’s maneuver to rise from the floor independently. Validation of prediction models using independent data, and extension to predictions over longer follow-up periods, will be important for practical applications.