Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies (ENVISION)

ENVISION: Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies

This is a multicenter, prospective, 2-year observational study in infants and children with developmental and epileptic encephalopathies (DEEs). The DEE currently being investigated is SCN1A-positive Dravet Syndrome.

Study Overview

• Status: Terminated
• Conditions: Dravet Syndrome
• Intervention / Treatment: Other: No Intervention

Detailed Description

This prospective, longitudinal, natural history master protocol has been designed to define the seizure, neurodevelopmental, and behavioral characteristics of SCN1A-positive Dravet Syndrome in infants and children between 6 and 60 months. It will also explore the impact of the disease on the participant's parent/caregiver quality of life (QoL) and healthcare resource utilization (HCRU).

• Study Type: Observational
• Enrollment (Actual): 58

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital - Melbourne Brain Centre
• Spain
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
  • Valencia, Spain
    • Hospital Universitari i Politecnic La Fe
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • San Francisco, California, United States, 94143
      • UCSF Benioff Children's Hospital
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northeast Regional Epilepsy Group
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Abigail Wexner Research Institute at Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 5 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Infants and children aged between 6 and 60 months with SCN1A-positive Dravet Syndrome.

Description

Inclusion Criteria:

• Aged between 6 months and 60 months.
• Confirmed SCN1A mutation.
• Normal development prior to onset of first seizure as defined by the Centers for Disease -Control and Prevention (CDC 2019).
• Onset of seizures between age 3 and 15 months, inclusive.

Exclusion Criteria:

• Copy number variant of SCN1A, including SCN1A microdeletion, if affecting other genes.
• SCN1A mutation present on both alleles.
• Known pathogenic or clinically suspected mutation in a seizure-associated gene besides SCN1A.
• Confirmed mutation in a gene besides SCN1A that is known to increase the severity of the seizure phenotype.
• Known gain-of-function genetic mutation, as defined by functional studies, including p.Thr226Met.
• History of notable developmental deficit that was evident prior to seizure onset.
• Known central nervous system structural abnormality as found on magnetic resonance imaging or computed tomography scan of brain.
• Currently taking or has taken for 6 or more consecutive weeks anti-seizure medications (ASMs) at a therapeutic dose that are contraindicated in SCN1A-positive Dravet Syndrome, including sodium channel blockers.
• Known concomitant genetic mutation or clinical comorbidity that potentially confounds typical Dravet phenotype.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SCN1A-positive Dravet Syndrome; Participants aged between 6 and 60 months of age who have SCN1A-positive Dravet Syndrome. Clinical, neurocognitive, laboratory, the burden of disease, and health care resource utilization will be assessed.	Other: No Intervention; No Intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure burden	Measured using monthly seizure frequency derived from seizure diaries.	Change from Baseline at 24 months
Seizure freedom	Measured using the proportion of seizure-free days observed.	Change from Baseline at 24 months
Use of anti-seizure medication(s)	Measured using the incidence of anti-seizure medication usage observed during the 60 days leading up to each nominal visit.	Baseline through Month 24
Use of Special Diet	Measured using the incidence of ketogenic/high-fat diet usage observed during the 60 days leading up to each nominal visit.	Change from Baseline at 24 months
Cognitive functioning	Measured using composite scores from 3 domains in the Bayley Scales of Infant and Toddler Development (3rd Edition) instrument. Domains include: (1) Cognitive; (2) Language; (3) Motor. Composite scores are normalized to a mean and SD of 100 and 15, respectively (range is not applicable as the scores are unbounded). Higher scores correspond to better outcomes compared to a normal population.	Change from Baseline at 24 months
Behavioral and social functioning	Measured using raw scores from 2 domains in the Brief Infant Toddler Social Emotional Assessment. Domains include: (1) Problem; and (2) Competence. Domain raw scores range from 31 to 93 and 11 to 33 for the Problem and Competence domains, respectively. Higher Problem scores correspond to worse outcomes. Higher Competence scores correspond to better outcomes	Change from Baseline at 24 months
Motor functioning	Measured using categorical outcomes of 7 motor items adapted from the Bayley Scales of Infant and Toddler Development instrument and NorthStar Ambulatory Assessment. Motor milestones include: (1) Sit unassisted for 30 seconds; (2) Walk with assistance; (3) Stand alone; (4) Walk alone; (5) Walk upstairs; (6) Run with Coordination; and (7)Jump forward.	Baseline through Month 24
Incidence of Adverse Events	Measured using the incidence of adverse events and serious adverse events (broken down by preferred term) observed during the study.	Baseline through Month 24
Overall survival	Measured using the incidence of death observed by a given time point during the study.	Baseline through Month 24

Collaborators and Investigators

• Sponsor: Encoded Therapeutics
• Investigators: Study Director: Salvador Rico, M.D., Ph.D, Encoded Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 3, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: epilepsy; DEE; severe myoclonic epilepsy of infancy; severe myoclonic epilepsy; SMEI; SCN1A related seizure disorder; epileptic encephalopathy; developmental and epileptic encephalopathies
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Epilepsy; Epilepsies, Myoclonic; Brain Diseases
• Other Study ID Numbers: ETX-DS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Plan is undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No