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

Overview

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.

Full Title of Study: “ENVISION: Natural History Study of Infants and Children With Developmental and Epileptic Encephalopathies”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: March 31, 2023

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).

Interventions

  • Other: No Intervention
    • No Intervention

Arms, Groups and Cohorts

  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Seizure burden
    • Time Frame: Change from Baseline at 24 months
    • Measured using monthly seizure frequency derived from seizure diaries.
  • Seizure freedom
    • Time Frame: Change from Baseline at 24 months
    • Measured using the proportion of seizure-free days observed.
  • Use of anti-seizure medication(s)
    • Time Frame: Baseline through Month 24
    • Measured using the incidence of anti-seizure medication usage observed during the 60 days leading up to each nominal visit.
  • Use of Special Diet
    • Time Frame: Change from Baseline at 24 months
    • Measured using the incidence of ketogenic/high-fat diet usage observed during the 60 days leading up to each nominal visit.
  • Cognitive functioning
    • Time Frame: Change from Baseline at 24 months
    • 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.
  • Behavioral and social functioning
    • Time Frame: Change from Baseline at 24 months
    • 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
  • Motor functioning
    • Time Frame: Baseline through Month 24
    • 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.
  • Incidence of Adverse Events
    • Time Frame: Baseline through Month 24
    • Measured using the incidence of adverse events and serious adverse events (broken down by preferred term) observed during the study.
  • Overall survival
    • Time Frame: Baseline through Month 24
    • Measured using the incidence of death observed by a given time point during the study.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 6 Months

Maximum Age: 60 Months

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Encoded Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Salvador Rico, M.D., Ph.D, Study Director, Encoded Therapeutics

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.