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Dravet Syndrome clinical trials

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NCT ID: NCT06371794 Enrolling by invitation - Dravet Syndrome Clinical Trials

EXploring novEl Molecular Determinants of DRAvet Syndrome Phenotype Heterogeneity

EXEDRA
Start date: July 6, 2023
Phase: N/A
Study type: Interventional

Dravet syndrome is characterized as a developmental encephalopathy resulting from mutations of SCN1A, the gene encoding the alpha subunit of the voltage-gated sodium channel Nav1.1. The syndrome typically presents with drug-resistant epilepsy and varying degrees of cognitive disorders. Current treatment efficacy may be hindered by insufficient knowledge of undiscovered molecular determinants of the disease and its heterogeneous nature. Utilizing induced pluripotent stem cells (iPSCs) derived from skin biopsies, accessibility to patients' brain neurons has enabled successful modeling of various genetic neurological diseases. Neurons and brain organoids will be obtained from Dravet syndrome patients exhibiting diverse phenotypic severities, encompassing behavioral and developmental delays, to discern the molecular determinants of phenotypic diversity. Specifically, emphasis will be placed on investigating cellular and molecular mechanisms linking altered neuronal excitability with synaptic dysfunction.The study will focus on exploring the expression of newly identified modifiers potentially associated with neuronal excitability and synaptic function in iPSC-derived human neurons. This aims to establish correlations between the severity of epileptic and cognitive phenotypes and the altered expression of these proteins, whose functions are not fully understood.In the mid to long term, efforts will be directed towards overcoming the limitations of conventional therapeutic approaches for Dravet syndrome. This will involve attempting to reverse the observed morphological and functional alterations in Dravet syndrome neurons using viral vectors to promote overexpression/downregulation of identified modifiers correlated with disease severity. The anticipated outcomes of this project are expected to unveil novel molecular mechanisms underlying the pathophysiology of this severe neurogenetic disease, characterized by varying degrees of cognitive impairment. Moreover, these findings may pave the way for the discovery of innovative therapeutic strategies.

NCT ID: NCT06283212 Recruiting - Dravet Syndrome Clinical Trials

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

UK Only
Start date: April 15, 2024
Phase: Phase 1/Phase 2
Study type: Interventional

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.

NCT ID: NCT06149663 Available - Dravet Syndrome Clinical Trials

Intermediate-Size Expanded Access Protocol (EAP) for LP352

Start date: n/a
Phase:
Study type: Expanded Access

This is an intermediate-size expanded access program (EAP) study. The purpose of this EAP is to provide continued access to LP352, an investigational drug product being investigated in patients with Developmental and Epileptic Encephalopathies (DEEs). The EAP study will allow continued treatment with LP352 for eligible patients diagnosed with treatment resistant DEEs who successfully completed an LP352 Clinical Trial (Enrollment by Invitation).

NCT ID: NCT06118255 Recruiting - Dravet Syndrome Clinical Trials

A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome

ORCHID
Start date: May 21, 2024
Phase: Phase 3
Study type: Interventional

The primary purpose of this study is evaluate the safety and tolerability of fenfluramine hydrochloride (HCl) 0.2 to 0.8 mg/kg/day in infants 1 year to less than 2 years of age with Dravet syndrome.

NCT ID: NCT06112275 Recruiting - Dravet Syndrome Clinical Trials

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

Start date: March 2024
Phase: Phase 1/Phase 2
Study type: Interventional

WAYFINDER is a Phase 1/2 study in Australia to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged 36 to <84 months (3 to <7 years). The study follows an open-label, dose-escalation design.

NCT ID: NCT05651204 Recruiting - Dravet Syndrome Clinical Trials

GABA Biomarkers in Dravet Syndrome

Start date: September 8, 2022
Phase:
Study type: Observational

This study will non-invasively obtain levels of GABA in the brain of children with SCN1A+DS and neurodeveloping children through evoked and induced cortical responses, correlate them with the BOLD responses, and with the levels of GABA in their blood.

NCT ID: NCT05635266 Recruiting - Stroke Clinical Trials

Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives

Start date: October 26, 2021
Phase:
Study type: Observational

To collect, preserve, and/or distribute annotated biospecimens and associated medical data to institutionally approved, investigator-directed biomedical research to discover and develop new treatments, diagnostics, and preventative methods for specific and complex conditions.

NCT ID: NCT05626634 Active, not recruiting - Dravet Syndrome Clinical Trials

Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy

Start date: November 8, 2022
Phase: Phase 2
Study type: Interventional

The objective of this study is to assess the long-term safety, tolerability, and efficacy of adjunctive therapy of LP352 in subjects with developmental and epileptic encephalopathies who completed participation in Study LP352-201.

NCT ID: NCT05560282 Not yet recruiting - Dravet Syndrome Clinical Trials

Fenfluramine for Adult Dravet Patients

Start date: December 10, 2022
Phase: Phase 3
Study type: Interventional

Full Title: Fenfluramine for the treatment of refractory Epilepsy in Adult Dravet patients Short Title: Fenfluramine for Adult Dravet patients Clinical Phase: Phase III Sample Size: A total of 15 participants will be included in the study. Study Population: Adult patients (18 years and older) with drug-resistant epilepsy (maintained on their existing medications, with exception of cannabidiol) and genetically confirmed Dravet syndrome will be recruited to participate in the study. Accrual Period: 12 months Study Design: Open label, non-randomized and uncontrolled add-on trial in adults (18 years of age and older) residing in Ontario, with refractory motor seizures and maintained on their existing antiepileptic medications, with exception of cannabidiol. Study Duration: • Treatment period: 12 months Study duration: 28 months Study Agent/ Intervention/ Procedure: Name of study drug: fenfluramine (FINTEPLA) Dose and frequency: starting at 0.1 mg/kg twice daily, maximum 26 mg/day, in patients not taking concomitant stiripentol; starting at 0.1 mg/kg twice daily, maximum of 17 mg/day in patients taking concomitant stiripentol. All doses are divided to twice a day. Duration: Baseline phase: 4 weeks (no study drug) Titration phase: 2 weeks (if not taking stiripentol) to 3 weeks (if the patient is taking stiripentol) Treatment phase: 12 weeks Extension phase: up to 38 weeks, for patients who had at least a 50% decrease in seizure frequency Post-trial washout phase: 2 weeks (if not taking stiripentol) to 3 weeks (if the patient is taking stiripentol) Route of administration: Oral Efficacy and safety points of interest - Monthly convulsive seizure frequency (MCSF) reduction ≥ 50% - Improvement in motor function - Improvement in Cognition and Behavior - Improvement in Quality of Sleep - Improvement in Quality of life - Determination of Cardiovascular safety in adults - Responder analysis (≥25%, ≥75%, or 100% reduction in mean MCSF) - Longest period of seizure freedom - Number of Emergency room visits - Use of rescue medication (number of days in 28 day-periods) - Duration of post-ictal stage - Frequency of other seizure types - Body weight changes - Patient's global functioning prior to and after study (Clinical Global Impressions Scale) Trial registration: www.clinicaltrials.gov

NCT ID: NCT05544058 Recruiting - Dravet Syndrome Clinical Trials

Retrospective Non-interventional Study of Stiripentol Use in Dravet Patients in the USA

Start date: April 27, 2022
Phase:
Study type: Observational

The present study aims to collect data regarding the history of the disease, previous and current treatments, and the clinical status of Dravet patients during the 3 months prior to stiripentol initiation, the first 3 months on stiripentol and the last 3 months on stiripentol (irrespective of stiripentol discontinuation).