Clinical trial

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

NCT05419492

Name

ETX-DS-002

Description

ENDEAVOR is a Phase 1/2, 2-part, multicenter study to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged 6 to \<36 months. Part 1 follows an open-label, dose-escalation design, and Part 2 is a randomized, double-blind, sham delayed-treatment control, dose-selection study.

Trial arms

Trial start

2024-04-01

Estimated PCD

2027-04-01

Trial end

2031-04-01

Status

Recruiting

Phase

Early phase I

Treatment

ETX101

ETX101 is a non-replicating, recombinant adeno-associated viral vector serotype 9 (rAAV9) comprising a GABAergic regulatory element (reGABA) and an engineered transcription factor that increases transcription of the SCN1A gene (eTFSCN1A). ETX101 is intended as a one-time intracerebroventricular (ICV) administration.

Arms:

Part 1, Part 2

Size

Primary endpoint

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 a fatal outcome.

Day 1 through Study Completion

Percent change in monthly countable seizure frequency (MCSF) period, with countable seizures defined as generalized tonic-clonic/clonic, focal motor with clearly observable clinical signs, tonic, or atonic seizures.

Between the 8-week baseline period (prior to Day 1) and the 48-week post dosing period (defined as Week 5 through Week 52)

Eligibility criteria

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 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, including under an expanded access and/or compassionate use program. * Participant has clinically significant underlying liver disease.

Protocol

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Updated at

2024-04-17

1 organization

1 product

1 indication

Organization

Encoded Therapeutics

Product

ETX101

Indication

Dravet syndrome