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

Dravet Syndrome Clinical Trial

— UK Only  

Official title:

EXPEDITION: 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: NCT06283212
• Other study ID #: ETX-DS-005
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 15, 2024
• Est. completion date: December 2029

Study information

• Verified date: June 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

EXPEDITION is a Phase 1/2 study in the UK to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet Syndrome aged 6 to < 48 months. The study follows and 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: 6 Months to 47 Months

Eligibility

Inclusion Criteria:

• Participant has a predicted loss of function pathogenic or likely pathogenic SCN1A variant

• Participant must have experienced their first seizure between the age of 3 and 15 months

• Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have 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.

• 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
United Kingdom	Queen Elizabeth Hospital	Glasgow
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Sheffield Children's Hospital	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Encoded Therapeutics

Country where clinical trial is conducted

United Kingdom, 

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 fatal outcome.		Day 1 through Study Completion, an average of 5 years
Primary	Change from baseline in the standard score of the Vineland Adaptive Behavior Scales - Third Edition Adaptive Behavior Composite at Week 52.		Baseline to 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.
Secondary	Percent change in monthly countable seizure frequency (MCSF) to 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)
Secondary	Change from baseline in the raw score of the Bayley Scales of Infant and Toddler Development® 4th Edition receptive language sub-domain at Week 52.		Baseline to Week 52. Raw scores range from 0 to 49 and higher scores correspond to better outcomes.