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

Primary Purpose

Dravet Syndrome

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

ETX101

About this trial

This is an interventional treatment trial for Dravet Syndrome focused on measuring Dravet, SCN1A, DEE, developmental and epileptic encephalopathy, Dravet Syndrome, SCN1A-positive, SCN1A+

Eligibility Criteria

6 Months - 36 Months (Child)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Part 1

Part 2

Arm Description

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

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.

Outcomes

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.

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.

Proportion of participants free from episodes of prolonged seizures and/or status epilepticus.

Secondary Outcome Measures

Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF).

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.

Full Information

NCT ID

NCT05419492

First Posted

June 10, 2022

Last Updated

June 10, 2022

Sponsor

Encoded Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT05419492

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

December 2022 (Anticipated)

Primary Completion Date

February 2026 (Anticipated)

Study Completion Date

October 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Encoded Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Dravet Syndrome

Keywords

Dravet, SCN1A, DEE, developmental and epileptic encephalopathy, Dravet Syndrome, SCN1A-positive, SCN1A+

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes 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

Allocation

Randomized

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1

Arm Type

Experimental

Arm Description

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

Arm Title

Part 2

Arm Type

Sham Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

ETX101

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time Frame

Day 1 through Week 52

Title

Time Frame

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)

Title

Proportion of participants free from episodes of prolonged seizures and/or status epilepticus.

Time Frame

Day 1 through Week 52

Secondary Outcome Measure Information:

Title

Proportion of participants with ≥ 90% reduction in monthly countable seizure frequency (MCSF).

Time Frame

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).

Title

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.

Time Frame

Baseline through Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

36 Months

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Encoded Patient Advocacy

Phone

+1 (650) 398-4301

patientadvocacy@encoded.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Salvador Rico, M.D., Ph.D

Organizational Affiliation

Encoded Therapeutics

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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