Clinical trial readiness and validation of onsite and remote evaluation in valosin containing protein-associated multisystem proteinopathy

Topic:

Translational Research

Poster Number: M254

Author(s):

Megan Iammarino, DPT, Nationwide Children's Hospital, Natalie Reash, PT, DPT, Nationwide Children's Hospital, Lindsay Pietruszewski, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Christopher Steiner, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Melissa Smith, DPT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Linda Lowes, PT, PhD, Nationwide Children's Hospital, Jerry Mendell, MD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Anne M. Connolly, MD, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Zarife Sahenk, MD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Kathleen Adderley, Abigail Wexner Research Institute at Nationwide Children's Hospital, Eleonora D'Ambrosio, MD, Abigail Wexner Research Institute at Nationwide Children's Hospital, Audrey Beale, Abigail Wexner Research Institute at Nationwide Children's Hospital, Lauren Humphrey, Abigail Wexner Research Institute at Nationwide Children's Hospital, Nathan Peck, Cure VCP Disease, Inc., Allison Peck, Cure VCP Disease, Inc., Lindsay Alfano, DPT, Nationwide Children's Hospital

Background: Valosin containing protein-associated multisystem proteinopathy (MSP1), previously known as inclusion body myopathy with Paget’s disease of the bone and frontotemporal dementia (IBMPFD), is a dominantly inherited, rare disorder of multisystemic involvement that results in a heterogeneous presentation of progressive weakness, bone disease, frontotemporal dementia, cardiac, respiratory, and/or bulbar dysfunction. The variability in patient disease onset and presentation highlights the need for a prospective clinical trial readiness study to inform future clinical trial design.
Objectives: Subjects will complete a combination of in-home, remote assessments and annual visits in the standardized clinic environment, across a 2-year period. A battery of functional and patient-reported clinical outcome assessments (COA) will be completed at each visit. We additionally aim to establish the reliability and validity of remote-based video assessments, with the goal of limiting patient travel burden.
Results: Forty-three subjects (mean age: 50.9 years (range: 28-71)) with genetically-confirmed MSP1 have enrolled and were followed up to 2 years, with a total of 230 visits completed in 6-month intervals, to-date. Test-retest reliability was excellent within and between visit types (ICC≥0.8; P<0.001). Twenty patients have completed 2-years of study visits; significant changes in motor and pulmonary function over the course of one and two years were detected and the change in motor performance was consistent with both patient and clinician global impression of change. Exploration into genotype-phenotype relationships in our cohort will be highlighted. Cohort level feasibility and performance of all COA, sensitivity to change and meaningful change on included assessments over 2-years will also be presented Conclusions: The functional COAs with the greatest variability between the home and clinic environment highlight the need for standardized equipment and furniture if remote assessments are implemented in clinical trials. The COAs selected quantify change in motor function over time in this cohort.