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

NCT06112275 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: ETX-DS-004
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

WAYFINDER is a Phase 1/2 study in Australia to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged 6 to \<84 months. The study follows an open-label, dose-escalation design.

Conditions

Dravet Syndrome

Keywords

Dravet; SCN1A; DEE; developmental and epileptic encephalopathy; Dravet Syndrome; SCN1A-positive; SCN1A+

Outcome Measures

Primary Outcomes (3)

• Proportion 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 a fatal outcome.

  Day 1 through Study Completion, an average of 5 years

• Percent change from Baseline in monthly countable seizure frequency (MCSF) at 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)

• Proportion of participants free from episodes of prolonged seizures and/or status epilepticus at Week 52.

  Week 5 through Week 52

Secondary Outcomes (2)

• Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF) from Baseline at Week 52.

  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 Vineland-Third Edition Expressive Communication raw score at Week 52.

  Baseline through Week 52. 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 - 83 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant must have a predicted loss of function pathogenic or likely pathogenic SCN1A variant.
• Participant must have experienced their first seizure between the ages of 3 and 15 months.
• Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have a 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 6-month 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 (1)

The Royal Children's Hospital

Melbourne, Australia

Location

MeSH Terms

Conditions

Epilepsies, Myoclonic; Generalized Epilepsy With Febrile Seizures Plus, Type 2

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: October 25, 2023
• First Posted: November 1, 2023
• Study Start: February 28, 2024
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: November 14, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)