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)

Sponsor

Encoded Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06112275

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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 36 to 83 months (3 to <7 years). The study follows an open-label, dose-escalation design.

Condition or Disease	Intervention/Treatment	Phase
Dravet Syndrome	Drug: ETX101	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

4 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2024

Anticipated Primary Completion Date :

Dec 1, 2029

Anticipated Study Completion Date :

Dec 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort X Cohort X will consist of 2 participants and will evaluate ETX101 dose level 1.	Drug: ETX101 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).
Experimental: Cohort Y Cohort Y will consist of 2 participants and will evaluate ETX101 dose level 2.	Drug: ETX101 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).

Arm

Intervention/Treatment

Experimental: Cohort X

Cohort X will consist of 2 participants and will evaluate ETX101 dose level 1.

Drug: ETX101

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).

Experimental: Cohort Y

Cohort Y will consist of 2 participants and will evaluate ETX101 dose level 2.

Drug: ETX101

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Adaptive Behavior Scales - Third Edition score at Week 52. [Baseline through 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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

36 Months to 83 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must have a predicted loss of function pathogenic or likely pathogenic SCN1A variant.
Participant must have experienced their first convulsive 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.