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

Официальное название

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

Обзор

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 1A), aged ≥48 months to \<18 years (Part 1B), and aged ≥6 to \<48 months (Part 2). Part 1A follows an open-label, dose-escalation design, Part 1B follows an open-label design, and Part 2 is a randomized, double-blind, sham delayed-treatment control study.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Percent change in monthly countable seizure frequency (MCSF) between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period. [Срок оценки: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).]

Вторичные конечные точки (10)

• Change from Baseline in Bayley-4 cognitive subdomain raw score at Week 52 (Key Secondary Endpoint for Part 2). [Срок оценки: From Baseline to Week 52.]
• Change from Baseline in Vineland-3 subdomain GSVs at Week 52. [Срок оценки: From Baseline to Week 52.]
• Change from Baseline in Bayley-4 subdomain GSVs at Week 52. [Срок оценки: From Baseline to Week 52.]
• Proportion of participants achieving ≥ 75% reduction in MCSF between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period. [Срок оценки: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).]
• Proportion of participants achieving ≥ 50% reduction in MCSF between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period. [Срок оценки: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).]
• Change from Baseline in the Vineland-3 Adaptive Behavior Composite standard score at Week 52. [Срок оценки: From Baseline to Week 52.]
• Change from Baseline in Vineland-3 subdomain raw scores at Week 52. [Срок оценки: From Baseline to Week 52.]
• Change from Baseline in Bayley-4 subdomain raw scores (excluding cognitive subdomain) at Week 52. [Срок оценки: From Baseline to Week 52.]
• Proportion of CGI-I responders, defined as participants with a CGI-I score of 1 (Very much improved) or 2 (Much improved), at Week 52. [Срок оценки: From Baseline to Week 52.]
• Proportion of CGI-S responders, defined as participants who either have a CGI-S score of 1 (Normal, not at all ill) or demonstrate a ≥2 point improvement from Baseline, at Week 52. [Срок оценки: From Baseline to Week 52.]

Критерии участия

Критерии включения

• Participant must be aged between ≥6 months and <36 months in Part 1A, ≥48 months and <18 years in Part 1B, ≥6 months 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.

Критерии исключения

• 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 has received sodium channel blockers during the Pre-Dosing Seizure Period.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 11 центров

• UCSF Benioff Children's Hospitals — San Francisco
• Colorado Children's Hospital — Aurora
• Nicklaus Children's Hospital — Miami
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago
• Boston Children's Hospital — Boston
• Mott Children's Hospital — Ann Arbor
• Mayo Clinic — Rochester
• Duke Children's Hospital & Health Center — Durham
• … и ещё 3 центра

Великобритания · 2 центра

• Queen Elizabeth Hospital — Glasgow
• Great Ormond Street Hospital — London

Австралия · 1 центр

• The Royal Children's Hospital — Melbourne

Идентификаторы

NCT: NCT05419492 · ETX-DS-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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