Development of Pediatric and Adult LGMD2I/R9 Disease Specific Physical Function Questionnaires Using PROMIS Item Banks


Clinical Trials

Poster Number: T369


Divya B. Reddy, MD, ML Bio Solutions, a BridgeBio company, Beth Leiro, ML Bio Solutions, a BridgeBio company, Katherine Mathews, MD, FAAN, University of Iowa, John Vissing, MD, DMSci, Rigshospitalet, University of Copenhagen

Background: LGMD2I/R9 is caused by bi-allelic partial loss-of-function of the fukutin-related protein (FKRP) gene, resulting in hypoglycosylation of α-dystroglycan (αDG) and progressive muscle damage. FORTIFY (NCT05775848) is a Phase 3 multinational double-blind placebo-controlled study enrolling individuals aged 12-60 years with LGMD2I/R9. BBP-418 is an oral substrate intended to saturate the partially functional FKRP enzyme, driving increased glycosylation of αDG, and potentially ameliorating the root cause of LGMD2I/R9. Although physical function deficits are well documented in LGMD2I/R9, there are no disease specific PROs that assess the impact of these deficits on daily life. Our aim was to develop disease specific physical function PROs to assess the impact of impaired physical function in individuals with LGMD2I/R9.

Methods: Items from the PROMIS Pediatric and Adult Physical Function Item Banks were selected to create custom Physical Function PROMIS questionnaires. The items were methodically chosen to include LGMD2I/R9 disease concepts of interest, with careful consideration to ensure that the selection of items was informed by a variety of sources and covered a broad range of physical function.
Item selection was informed by the following criteria:
Proximal Weakness: The impact of proximal weakness on mobility and activities of daily living was assessed, and items relying on proximal strength were selected.
ACTIVLIM: This PRO assesses activity limitations in patients with neuromuscular disorders and items on the PROMIS item banks that overlapped with ACTIVLIM items selected.
Patient Experience: We included information from a patient survey commissioned by the sponsor to gather insights from the LGMD2I/R9 patient community about disease burden and transcripts from Patient Day where patients shared their experiences of living with LGMD2I/R9.
KOL Endorsement: A round table was convened with LGMD2I/R9 physician specialists for guidance and endorsement of selected items.

Conclusion: LGMD2I/R9 specific physical function questionnaires for adults and children were created using the PROMIS Item Banks. Validation studies and correlation of PRO data with standardized performance measures are planned. If validated, this PRO can be a useful addition to clinical trials, such as FORTIFY.