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)

Dravet Syndrome Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06112275
• Other study ID #: ETX-DS-004
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2024
• Est. completion date: December 2029

Study information

• Verified date: February 2024
• Source: Encoded Therapeutics
• Contact: Encoded Patient Advocacy
• Phone: +1 (650) 398-4301
• Email: patientadvocacy[@]encoded.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 <84 months (3 to <7 years). The study follows an open-label, dose-escalation design.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4
• Est. completion date: December 2029
• Est. primary completion date: December 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 36 Months to 83 Months

Eligibility

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.

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Syndrome

Intervention

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).

Locations

Country	Name	City	State
Australia	The Royal Children's Hospital	Melbourne

Sponsors (1)

Lead Sponsor	Collaborator
Encoded Therapeutics

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Primary	Proportion of participants free from episodes of prolonged seizures and/or status epilepticus at Week 52.		Week 5 through Week 52
Secondary	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)
Secondary	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.