Clinical trial NCT05419492: A Clinical Study to Evaluate the Safety and Efficacy of ETX101 in Infants and Children With SCN1A-Positive Dravet Syndrome
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Dravet Syndrome
Keywords: Dravet
SCN1A
DEE
developmental and epileptic encephalopathy
Dravet Syndrome
SCN1A-positive
SCN1A+
Lead sponsor: Encoded Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-06-15
Enrollment: 22
Sex: ALL
Minimum age (years): 6
Maximum age (years): 47
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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) and aged ≥6 to \<48 months (Part 2). Part 1 follows an open-label, dose-escalation design, and Part 2 is a randomized, double-blind, sham delayed-treatment control, dose-selection study.


Eligibility criteria: Inclusion Criteria:

* Participant must be aged between ≥6 months and \<36 months in Part 1 and \<48 months in Part 2.
* Participant must have a predicted loss of function pathogenic or likely pathogenic SCN1A variant.
* Participant must have experienced their first 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.

Primary outcomes:
measure: 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.
timeFrame: Day 1 through Study Completion
measure: 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.
timeFrame: Between the pre-dose period (Part 1: 30 days prior to consent and the collection period through Day -1; Part 2: collection period between Day -72 and Day -1) and the 48-week post dosing period (defined as Week 5 through Week 52)
Secondary outcomes:
measure: Absolute change in monthly countable seizure frequency (MCSF)
timeFrame: Between the pre-dose period (Part 1: 30 days prior to consent and the collection period through Day -1; Part 2: collection period between Day -72 and Day -1) and the 48-week post dosing period (defined as Week 5 through Week 52)
measure: Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF).
timeFrame: Between the pre-dose period (Part 1: 30 days prior to consent and the collection period through Day -1; Part 2: collection period between Day -72 and Day -1) and the 48-week post dosing period (defined as Week 5 through Week 52)
measure: Change from baseline in the Vineland-3 Expressive Communication raw score at Week 52
timeFrame: Baseline through Week 52
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospitals
state: California
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
Study officials:
affiliation: Encoded Therapeutics
name: Salvador Rico, M.D., Ph.D
role: STUDY_DIRECTOR
References: