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

Sponsor

Encoded Therapeutics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04537832

Collaborator

(none)

Enrollment

Locations

37.4

Anticipated Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Dravet Syndrome	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 Design

Study Type:

Observational

Actual Enrollment :

58 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 18, 2021

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

Seizure burden [Change from Baseline at 24 months]
Measured using monthly seizure frequency derived from seizure diaries.
Seizure freedom [Change from Baseline at 24 months]
Measured using the proportion of seizure-free days observed.
Use of anti-seizure medication(s) [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 [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 [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 [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 [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 [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 [Baseline through Month 24]
Measured using the incidence of death observed by a given time point during the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 60 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	UCSF Benioff Children's Hospital	San Francisco	California	United States	94143
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Nicklaus Children's Hospital	Miami	Florida	United States	33155
5	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
6	Northeast Regional Epilepsy Group	Hackensack	New Jersey	United States	07601
7	Abigail Wexner Research Institute at Nationwide Children's Hospital	Columbus	Ohio	United States	43205
8	Oregon Health and Science University	Portland	Oregon	United States	97239
9	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
10	Le Bonheur Children's Hospital	Memphis	Tennessee	United States	38103
11	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
12	Multicare Institute for Research and Innovation	Tacoma	Washington	United States	98405
13	Austin Hospital - Melbourne Brain Centre	Heidelberg	Victoria	Australia	3084
14	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain
15	Hospital Universitari i Politècnic La Fe	Valencia		Spain
16	Queen Elizabeth Hospital	Glasgow		United Kingdom	G51 4TF