A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome

NCT06283212 | Active Not Recruiting Phase 1

• 1 other identifier: ETX-DS-005
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

EXPEDITION is a Phase 1/2 study in the UK to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet Syndrome aged 6 to \< 48 months. The study follows and open-label, dose-escalation design.

Conditions

Dravet Syndrome

Outcome Measures

Primary Outcomes (2)

• Proportions of participants experiencing any treatment-emergent adverse events (AEs), serious adverse events (SAEs), related AEs, AEs with severity Grade ≥ 3, AEs resulting in study discontinuation, and AEs with fatal outcome.

  Day 1 through Study Completion, an average of 5 years

• Change from baseline in the standard score of the Vineland Adaptive Behavior Scales - Third Edition Adaptive Behavior Composite at Week 52.

  Baseline to Week 52. Standard scores are normalized to a mean and SD of 100 and 15, respectively, and are not bounded by a range. Higher scores correspond to better outcomes.

Secondary Outcomes (2)

• Percent change in monthly countable seizure frequency (MCSF) to Week 52, with countable seizures defined as generalized tonic-clonic/clonic, focal motor with clearly observable clinical signs, tonic bilateral, and atonic seizures.

  Between the 8-week baseline period and the 48-week post-dosing assessment period (defined as Week 5 to Week 52 following administration of ETX101)

• Change from baseline in the raw score of the Bayley Scales of Infant and Toddler Development® 4th Edition receptive language sub-domain at Week 52.

  Baseline to Week 52. Raw scores range from 0 to 49 and higher scores correspond to better outcomes.

Study Arms (4)

Cohort A

EXPERIMENTAL

Cohort A will evaluate ETX101 dose level 1.

Drug: ETX101

Cohort B

EXPERIMENTAL

Cohort B will evaluate ETX101 dose level 2.

Drug: ETX101

Cohort C

EXPERIMENTAL

Cohort C will evaluate ETX101 dose level 3.

Drug: ETX101

Cohort D

EXPERIMENTAL

Cohort D will evaluate ETX101 dose level 4.

Drug: ETX101

Interventions

ETX101 DRUG

ETX101 is composed of a non-replicating, recombinant adeno-associated viral serotype 9 (rAAV9) vector used to deliver a GABAergic regulatory element (reGABA) and an engineered transcription factor that increases transcription of the SCN1A gene (eTFSCN1A)

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 6 Months - 47 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant has a predicted loss of function pathogenic or likely pathogenic SCN1A variant
• Participant must have experienced their first seizure between the age of 3 and 15 months
• Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have high clinical suspicion of a diagnosis of Dravet syndrome
• Participant is receiving at least one prophylactic antiseizure medication

You may not qualify if:

• Participant has another genetic mutation or clinical comorbidity which could potentially confound the typical Dravet phenotype
• Participant has a known central nervous system structural and/or vascular abnormality (indicated by an MRI or CT scan of the brain).
• Participant has an abnormality that may interfere with CSF distribution and/or has an existing ventriculoperitoneal shunt.
• Participant is currently taking or has taken antiseizure medications (ASMs) at a therapeutic dose that are contraindicated in Dravet syndrome, including sodium channel blockers.
• Participant has experienced seizure freedom for a period of 4 consecutive weeks within the 90-day period prior to informed consent.
• Participant has previously received gene or cell therapy.
• Participant is currently enrolled in a clinical trial or receiving an investigational therapy.
• Participant has clinically significant underlying liver disease.

Sponsors & Collaborators

• Encoded Therapeutics: lead

Study Sites (3)

Queen Elizabeth Hospital

Glasgow, G51 4TF, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N3JH, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, S10 2TH, United Kingdom

Location

MeSH Terms

Conditions

Epilepsies, Myoclonic

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; 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: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2024
• First Posted: February 28, 2024
• Study Start: May 9, 2024
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: December 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)