The ENVISION Study: An International, Prospective Natural History Study in Young Children with SCN1A+ Dravet Syndrome
Abstract number :
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Submission ID :
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 12:51 PM
Andreas Brunklaus, MD - Neurosciences Department Great Ormond Street Hospital NHS FoundationTrust and Developmental Neurosciences Programme of the UCL Institute of Child Health, London UK; Ingrid E. Scheffer, MBBD, PhD – Professor, University of Melbourne, Austin Health; M. Scott Perry – Cook Children’s Medical Center; James Wheless – Le Bonheur Children's Hospital; Joseph Sullivan – University of California at San Francisco; Kelly Knupp – The Children's Hospital Colorado; Colin Roberts – Doernbecher Children’s Hospital; Susana Boronat – Hospital de la Santa Creu i Sant Pau; Linda Laux – Ann & Robert H. Lurie Children's Hospital of Chicago; Patricia Smeyers – Hospital Universitari i Politècnic la Fe; Eric Segal – Northeast Regional Epilepsy Group; Deborah Holder – Children's Hospital Los Angeles; Anup Patel – Nationwide Children’s Hospital; Matthew Lallas – Nicklaus Children’s Hospital; Steven Phillips – Multicare Health System; Dennis Dlugos – Children’s Hospital of Philadelphia; Katherine Nickels – Mayo Clinic; Dennis Lal – Cleveland Clinic Lerner Research Institute; Elaine Wirrell – Mayo Clinic; Sameer Zuberi – Royal Hospital for Children; Sarah Christensen – Encoded Therapeutics; Jackie Gofshteyn – Encoded Therapeutics; Norman Huang – Encoded Therapeutics; Emma James – Encoded Therapeutics; Benit Maru – Encoded Therapeutics; Rosie O’Donnell – Encoded Therapeutics; Maria Candida Vila – Encoded Therapeutics; Salvador Rico – Encoded Therapeutics
Rationale: Dravet Syndrome (DS) is the prototypic developmental and epileptic encephalopathy characterized by drug-resistant seizures and developmental impairment. It typically begins with frequent and prolonged seizures in the first year of life in a healthy child, followed by developmental slowing, stagnation, or regression in subsequent years. Most children have a loss-of-function variation within the SCN1A gene. There is limited prospective long-term data describing the full range of phenotypic features and evolution, and the impact of DS on patients and families. ENVISION is a comprehensive observational study aimed at prospectively evaluating the natural course of neurodevelopmental status, adaptive functioning, motor functioning, sleep, quality of life, seizure frequency and types in young SCN1A+ DS patients. Data collected during the first 6 months of study will be presented.
Methods: Ongoing international, multicenter, longitudinal, prospective study of patients with DS with a confirmed SCN1A pathogenic variant, aged 6 months to 5 years at study entry. Participants are assessed remotely every 3 months (6 in-person) for 24 months to evaluate the longitudinal progression of various neurodevelopmental, motor, behavioral, social functioning, quality of life, sleep, and seizure endpoints using validated tools.
Results: At the time of analysis, 38 participants have been screened (mean age 36 months; 47.4% females, 68.4% white) and 11 have completed the baseline visit (mean age 41 months; 54.5% females, 81.8% white). During the 2 months leading up to the baseline visit (Day -60 to -1), the initial 11 participants were on an average of 3.5 antiseizure medications (SD 1.4), with clobazam (10/11), fenfluramine (9/11), cannabidiol (7/11), levetiracetam (3/11), and valproic acid (3/11) most frequently used. 10 participants completed the baseline Vineland Adaptive Behavior Scales (VABS) Version 3, with a trend of lower adaptive behavior composite (ABC) developmental quotients (DQ) with increasing age. The median VABS ABC DQ was 47.2, with the lowest median DQ coming from the Interpersonal Relationships subdomain (median 32.0), followed by Expressive Language (37.7), Receptive Language (38.8), and Play and Leisure (39.7). On an individual level, while the youngest participant (aged 22 months) showed the highest ABC DQ (81.8), the Interpersonal Relationships subdomain was already delayed (DQ of 40.9). Global developmental delay was found in 7 out of 8 participants who completed the baseline Bayley-III and WPPSI-IV.
Conclusions: Our initial data revealed high use of antiseizure medications and significant delay in adaptive functioning in young children with DS, which worsens over time. Communication and socialization subdomains are the most affected early in the course of their disease. Additional longitudinal data will be presented.
Funding: Please list any funding that was received in support of this abstract.: This abstract was supported by Encoded Therapeutics.