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

Sponsor

Encoded Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05419492

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 follows an open-label, dose-escalation design, and Part 2 is a randomized, double-blind, sham delayed-treatment control, dose-selection study.

Condition or Disease	Intervention/Treatment	Phase
Dravet Syndrome	Drug: ETX101	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Part 1 is open-label with no blinding. Part 2 will be conducted in a double-blinded manner whereby all Primary Site Staff (including clinicians, research coordinators, neuropsychologists, and physical therapists), study participants and caregivers, Sponsor and Sponsor-designees will be blinded through the end of Week 16 following Day 1 for a given participant. The Surgical Site Staff and Pharmacists will be unblinded to treatment assignment

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2026

Anticipated Study Completion Date :

Oct 1, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Part 1 will follow an open-label, rule-based, dose-escalation design and will initially evaluate 2 dose levels of ETX101 in participants.	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.
Sham Comparator: Part 2 Part 2 is a dose-selection study, which will follow a double-blind (up through Week 16), randomized, sham delayed-treatment control design There will be up to 3 cohorts in Part 2. Participants will be randomized 1:1:1 to study treatment (ie, Dose Level 1 or Dose Level 2) or sham procedure with delayed treatment. At the conclusion of Part 1, if the recommendation is made to proceed with a single dose level of ETX101 in Part 2, participants will be randomized 1:1 to study treatment or sham procedure with delayed treatment.	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.

Arm

Intervention/Treatment

Experimental: Part 1

Part 1 will follow an open-label, rule-based, dose-escalation design and will initially evaluate 2 dose levels of ETX101 in participants.

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.

Sham Comparator: Part 2

Part 2 is a dose-selection study, which will follow a double-blind (up through Week 16), randomized, sham delayed-treatment control design There will be up to 3 cohorts in Part 2. Participants will be randomized 1:1:1 to study treatment (ie, Dose Level 1 or Dose Level 2) or sham procedure with delayed treatment. At the conclusion of Part 1, if the recommendation is made to proceed with a single dose level of ETX101 in Part 2, participants will be randomized 1:1 to study treatment or sham procedure with delayed treatment.

Drug: ETX101

Outcome Measures

Primary Outcome Measures

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 Week 52]
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 First Assessment Period (which is the 12-week between Week 5 and Week 16)]
Proportion of participants free from episodes of prolonged seizures and/or status epilepticus. [Day 1 through Week 52]

Secondary Outcome Measures

Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF). [Between the 8-week baseline period (prior to Day 1) and the First Assessment Period (which is the 12-week period between Week 5 and Week 16).]
Absolute change in the raw score of the Bayley-III receptive language sub-domain. Domain raw scores range from 0 to 49 and higher scores correspond to better outcomes compared to a normal population. [Baseline through Week 52]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 36 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.