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

NCT04537832 | Terminated

• 1 other identifier: ETX-DS-001
• Study Type: observational
• Target: 58
• Locations: 4 countries
• Sites: 16

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.

Conditions

Dravet Syndrome

Keywords

severe myoclonic epilepsy; epilepsy; severe myoclonic epilepsy of infancy; SMEI; SCN1A related seizure disorder; epileptic encephalopathy; developmental and epileptic encephalopathies; DEE

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (1)

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

Interventions

No Intervention OTHER

No Intervention

SCN1A-positive Dravet Syndrome

Eligibility Criteria

• Age: 6 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Encoded Therapeutics: lead

Study Sites (16)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

Abigail Wexner Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Multicare Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Austin Hospital - Melbourne Brain Centre

Heidelberg, Victoria, 3084, Australia

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

Queen Elizabeth Hospital

Glasgow, G51 4TF, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum and Plasma

MeSH Terms

Conditions

Epilepsies, Myoclonic; Epilepsy

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Salvador Rico, M.D., Ph.D

  Encoded Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: September 3, 2020
• Study Start: January 18, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: June 12, 2023

Record last verified: 2023-06

Locations

AU (1); US (12); ES (2); GB (1)