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

Dravet Syndrome Clinical Trial

— ENVISION  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04537832
• Other study ID #: ETX-DS-001
• Status: Terminated
• Start date: January 18, 2021
• Est. completion date: March 31, 2023

Study information

• Verified date: June 2023
• Source: Encoded Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 58
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 60 Months

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Dravet Syndrome
• Epilepsies, Myoclonic
• Epilepsy

Intervention

Other:
• No Intervention
No Intervention

Locations

Country	Name	City	State
Australia	Austin Hospital - Melbourne Brain Centre	Heidelberg	Victoria
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari i Politècnic La Fe	Valencia
United Kingdom	Queen Elizabeth Hospital	Glasgow
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Abigail Wexner Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Northeast Regional Epilepsy Group	Hackensack	New Jersey
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Le Bonheur Children's Hospital	Memphis	Tennessee
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	UCSF Benioff Children's Hospital	San Francisco	California
United States	Multicare Institute for Research and Innovation	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Encoded Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizure burden	Measured using monthly seizure frequency derived from seizure diaries.	Change from Baseline at 24 months
Primary	Seizure freedom	Measured using the proportion of seizure-free days observed.	Change from Baseline at 24 months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Overall survival	Measured using the incidence of death observed by a given time point during the study.	Baseline through Month 24