G.P.389 - A prospective natural history study to measure progression of physical impairment, activity limitation and quality of life in Duchenne muscular dystrophy

Abstract

The aim of this study is to characterize the natural history and disease progression of Duchenne muscular dystrophy (DMD), capture biomarkers of safety and disease progression and provide comparative data for the development of rare exons for which formal controlled trials are not feasible. DMD is an X-linked, severely debilitating and fatal neuromuscular disorder caused by a deficiency in dystrophin. The 6-minute walking distance (6MWD) test is a validated endpoint for determination of DMD disease progression. Results from a 3-year, multicentre, exploratory, observational study in subjects with DMD, 3–18 years [life expectancy ≥ 3 years], will be presented. Study visits occurred at 6-month intervals from baseline, mirroring the usual pattern of clinic visits. Ambulant subjects were assessed using the 6MWD test, timed function tests (including rise from floor, 10-m walk/run, four-stair ascent/descent and supine to stand), North Star Ambulatory Assessment and DMD Functioning and Daily Activities Survey. Non-ambulant subjects were evaluated using Egen–Klassifikation. Other evaluations for all subjects included: muscle strength (handheld myometry); range of movement (handheld goniometer); myoset assessments (pinch, hand grip, moviplate); performance of upper limb; pulmonary function; physical examination (major events notable for disease progression: weight, height, body mass index); urinalysis; and blood sampling for biomarker assessment. Electrocardiography, cardiac echo and DEXA scan were assessed for subjects in whom they were performed. Data summaries at each visit are provided. A total of 269 subjects were enrolled from July 2012 to June 2014. This planned interim analysis includes 80 subjects (of whom 5 were non-ambulant) with data for 1 year. Demographic characteristics and changes from study baseline for key endpoints are presented. It is anticipated that data from this natural history study will inform the design of future clinical studies.