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)

Phase 1

Recruiting

• Conditions: Dravet Syndrome
• Interventions: Drug: ETX101

• Registration Number: NCT06112275
• Lead Sponsor: Encoded Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-25
• Study First Submitted QC: 2023-10-30
• Study First Posted: 2023-11-01
• Study Start: 2024-02-28
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-27
• Primary Completion: 2030-06
• Study Completion: 2030-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A	ETX101	Cohort A will evaluate ETX101 dose level 1.
Cohort B	ETX101	Cohort B will evaluate ETX101 dose level 2.
Cohort C	ETX101	Cohort C will evaluate ETX101 dose level 3.
Cohort D	ETX101	Cohort D will evaluate ETX101 dose level 4.

Primary Outcome Measures

Name	Time	Method
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 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
Proportion of participants free from episodes of prolonged seizures and/or status epilepticus at Week 52.	Week 5 through Week 52

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

The Royal Children's Hospital; 🇦🇺 Melbourne, Australia