A Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children With SCN1A-Positive Dravet Syndrome

Dravet Syndrome Clinical Trial

— ENDEAVOR  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05419492
• Other study ID #: ETX-DS-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2024
• Est. completion date: April 2031

Study information

• Verified date: April 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: April 2031
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 35 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 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.

Related Conditions & MeSH terms

• Dravet Syndrome
• Epilepsies, Myoclonic
• Syndrome

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	UCSF Benioff Children's Hospitals	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Encoded Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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)
Secondary	Proportion of participants with = 90% reduction in monthly countable seizure frequency (MCSF).		Between the 8-week baseline period (prior to Day 1) and the 48-week post dosing period (defined as Week 5 through Week 52).
Secondary	Change from baseline in the Vineland-3 Expressive Communication raw score at Week 52		Baseline through Week 52