Establishing Clinical Trial Readiness in patients age 0-5 years with LAMA2-related Congenital Muscular Dystrophy (READY CMD LAMA2)

Topic:

Clinical Trials

Poster Number: 317 T

Author(s):

Kevin Warf, BS, 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, Natalie Reash, DPT, Nationwide Children's Hospital, Minal Jain, PT DSc, National Institutes of Health, Christopher Steiner, DPT, Nationwide Children's Hospital, Sara Marshall, MS, Nationwide Children's Hospital, Rejuan Haque, PhD, The Ohio State University, Kaitlin Batley, MD, Children's Health/UT Southwestern, Katherine Mathews, MD, University of Iowa, Iowa City, Iowa, USA, Perry Shieh, MD, University of California Los Angeles, Hoda Abdel-Hamid, MD, University of Pittsburgh, Carolina Tesi Rocha, MD, Stanford University, Russell J. Butterfield, MD, PhD, University of Utah, Partha S. Ghosh, MD, Boston Children's Hospital, Peter Kang, MD, University of Minnesota, Nancy Kuntz, MD, Ann & Robert H. Lurie Children's Hospital of Chicago, Bo Hoon Lee, MD, University of Rochester, Cuixia Tian, MD, Cincinnati Children’s Hospital Medical Center, Michele Yang, MD, Children's Hospital Colorado, Craig M. Zaidman, MD, Department of Neurology, Washington University in St Louis, St Louis, MO, USA, Carsten G. Bönnemann, MD, habil., Neuromuscular and Neurogenetic Disorders of Childhood Section, NINDS, National Institutes of Health, Rebekah Camarata, CPNP-AC, Nationwide Children's Hospital, Megan Waldrop, MD, Nationwide Children's Hospital, The Ohio State College of Medicine, A. Reghan Foley, MD, MD(Res), Neuromuscular and Neurogenetic Disorders of Childhood Section, NINDS, National Institutes of Health, Anne Connolly, MD, Nationwide Children’s Hospital, Columbus, Ohio, USA 

Background: LAMA2-related Congenital Muscular dystrophy (CMD) in most affected children manifests in early infancy with severe weakness and progressive functional impairment. Early treatment likely holds the most promise for these children. The Ready-LAMA2 study (NCT06503367) is designed to determine optimal outcome measures for clinical trials for the youngest children with LAMA2 CMD.
Methods: Our study will enroll 40 children less than 5 years old with at least half of the cohort being less than 2.5 years of age at baseline. We will test which outcome measures (Bayley-4, Neuromuscular GRO, MFM20, and CHOP-INTEND), are 1) feasible, 2) reliable in person and remotely, and 3) responsive to change to establish the Minimal Clinically Important Difference (MCID). Remote functional assessments, if feasible, will allow us to minimize burden of study participation.
Results: All sites have completed in-person clinical evaluator (CE) training at Nationwide Children’s Hospital and 12 of 15 sites are activated. Enrollment started on 12 Jun 2025. Eight children (7 males) have been enrolled across 6 sites. An additional 7 are scheduled in the next 3 months. The average enrollment age is 3.6 years (one is less than 2.5 years). Intra-rater reliability for all functional assessments is excellent between Baseline and Day 2 in person and between Baseline and remote assessments within 2 weeks (0.945-0.996 ICC, across functional assessments). Baseline CK ranges from 298-1796 (U/L). No participants reported a history of seizures. Strength and function varied widely from ambulatory (n=1) to BiPAP dependent nocturnally (n=1). Four have G-tubes. Cognitive and language scores also varied widely.
Conclusion: Early LAMA2 clinical readiness data suggest feasibility across all functional outcomes after careful detailed training of all clinical evaluators. Responsiveness to change for these outcomes will be assessed across time.