Analysis of SV95C measurements, an e-digital mobility assessment in a real-life DMD population in GNT-014-MDYF natural history study

Topic:

Clinical Trials

Poster Number: V406

Author(s):

Silvana De Lucia, Institut I-Motion, Hôpital Trousseau, 26 avenue du Dr Arnold Netter, Paris, France;, Jean-Baptiste Davion, Service de Neurologie pédiatrique, CHU Lille, Avenue du Professeur Emile Laine, Lille , 59037 Lille,, Tristan Montier, CHU Morvan, Service de Génétique Médicale et Biologie de la Reproduction, 2 avenue Foch, 29200 Brest, Caroline Espil, Service de Neuropédiatrie, Hôpital des enfants Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux, F, Michaela Guglieri, MD, Institute of Genetic Medicine, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK, Laure Le Goff, Hôpital Femme Mère Enfant, 59 Boulevard Pinel, 69500 Bron, France;, Brigitte Chabrol, Hôpital d’Enfants, CHU Timone, 264 rue saint pierre, 13385 Marseille cedex 05 , France;, Andreea Seferian, MD, Institut I-Motion, Hôpital Trousseau, 26 avenue du Dr Arnold Netter, Paris, France;, Laurent Thibaut, Genethon, 1bis rue de l'international, Evry France;, Eric Guemas, BIOSSEC, 9 rue Anatole de la Forge, 75017 Paris, France;, Arnaud Valent, Genethon, 1bis rue de l'international, Evry France;, Fei Cao, Genethon, 1bis rue de l'international, Evry France;, Vincent Laugel, Hôpital de Hautepierre, 1 avenue Molière, 67098 Strasbourg Cedex, France;, Francesco Muntoni, MD, University College London

Duchenne Muscular Dystrophy (DMD) is a neuromuscular disease with significant clinical heterogeneity. Hospital based physiotherapist-assisted functional assessments are commonly used for monitoring in clinical and research settings. Stride Velocity at the 95th Centile (SV95C) captures daily ability using a wearable device in a real-life setting and therefore relies less on patient collaboration with assessment (e.g., young patients) or inter-evaluator variability. The European Medicines Agency (EMA) qualified SV95C as a primary endpoint in DMD. This analysis aims to explore its validity and normative data in a natural history (NH) study.

Seventy-seven DMD boys, aged 5-9 years, receiving steroids, and achieving an NSAA ≥18 were enrolled in a prospective NH study (GNT-014-MDYF). The SV95C and other clinical functional outcomes (e.g., NSAA) were measured every 6 months. Data were described for age subgroups (5-8Y and >8Y). SV95C accuracy was analyzed and compared to age-matched healthy (n=66) and DMD populations in the EMA SV95C Qualification Dossier (n=107). This included reliability assessed by intra-class correlation coefficient (ICC) with SV95C separated by 2 half recording periods. Spearman’s correlation was used to examine the consistency between different outcomes.

At baseline and 1-year, SV95C was highly reliable (ICC 0.97 at two timepoints), with clear separation from the healthy control and comparable to published data. At 1-year, mean changes in SV95C were -0.068m/s and -0.193m/s for 5-8Y and >8Y in GNT-014-MDYF patients (-0.263m/s and -0.226m/s for DMD patients of the same age from the EMA Dossier). This could be explained by the different baseline characteristics. Good correlations were observed between the SV95C and other physiotherapist-assisted outcomes (Correlation coefficient from +0.56 to +0.83).

This analysis demonstrated the validity of SV95C in a NH study with standardized follow-up and its consistency with published data. SV95C was sensitive to detect clinical change and correlated well with other clinical measures.