A Phase-2 Trial of 5mg/kg per week Prednisolone in Young Boys with DMD

Topic:

Clinical Trials

Poster Number: 72 S

Author(s):

Sara Marshall, MS, Nationwide Children's Hospital, Lindsay Alfano, PT, DPT, PCS, Nationwide Children's Hospital, Linda Lowes, PhD PT, Sarepta Therapeutics, Megan Iammarino, DPT, Nationwide Children's Hospital, Melissa Smith, PT, DPT, Nationwide Children's Hospital, Natalie Reash, DPT, Nationwide Children's Hospital, Lindsay Pietruszewski, PT, DPT, Nationwide Children's Hospital, Christopher Steiner, DPT, Nationwide Children's Hospital, Kevin Warf, BS, Nationwide Children's Hospital, Carson Richardson, MS, The Ohio State University, Alexa Craig, MD, Maine Health, Arpita Lakhotia, MD, University of Louisville and Norton Children’s Medical Group, Nancy Kuntz, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, Cuixia Tian, MD, Cincinnati Children’s Hospital Medical Center, Kaitlin Batley, MD, Children's Health/UT Southwestern, Kelly Lehman, MSN, CNP, Nationwide Children's Hospital, Lynsey Diersing, CNP, Nationwide Childrens Hospital, Megan Waldrop, MD, Nationwide Children's Hospital, The Ohio State College of Medicine, Anne Connolly, MD, Nationwide Children’s Hospital, Columbus, Ohio, USA 

A previous study demonstrated that twice weekly prednisolone (5mg/kg/dose) is effective in improving average motor function in boys with Duchenne muscular dystrophy (DMD). While adverse effects associated with daily corticosteroid use (Cushingoid features and impaired linear growth)—were not observed in this previous study, 56% increased weight percentile relative to baseline. Here, we investigate whether 5 mg/kg prednisolone once weekly provides comparable efficacy with less weight gain.
This multisite study has enrolled 19 participants across 3 different locations from 28Apr2021 to 26Mar2025. Five visits (one every 6 months) are conducted over two years. Functional motor outcomes include Bayley-4 Scales of Infant and Toddler Development (Bayley-4), Neuromuscular GRO and NSAA assessment tools. The Bayley-4 and the Adaptive Behavior Assessment System (ABAS) were used to assess language, cognition and social skills. Lastly, we have banked serum for future assessment of biomarkers related to the mechanism of action of once weekly corticosteroids.
Nineteen (of 30) participants have been enrolled (mean age: 1.5 years, range: 0.4-2.5). A positive correlation was present between baseline cognitive standard and gross motor scaled scores (R=0.57, p=0.011). Over the study period, gross motor function improved in all children, with mean GRO scores increasing from 55.9 (SD 12.8, N=10) at baseline to 73.4 (SD 3.9, N=10) at the end of the 24-month timepoint. However, “catchup” (i.e. improvement or stability (+/-1point) point in the Bayley-4 gross motor scaled score) was only seen in 7 of 13 participants at 12 months. Normal linear growth was maintained by all participants and the BMI also remained stable across baseline (17.7, SD=2.1, N=19), 12-month (17.7, SD 1.5, N=13), and 24-month (17.6, SD 1.6, N=10) timepoints. No cushingoid side effects developed and AM cortisol levels were normal throughout the study. Recognized confounders include worse gross motor delay in boys with mutations that include the brain promoter.