Dravet Syndrome

Researchers are evaluating ETX101, an investigational gene therapy delivered via AAV9, in infants and children with Dravet syndrome caused by SCN1A gene mutations. This study, called ENDEAVOR, includes participants from 6 months up to less than 18 years old and aims to assess the safety and effects of ETX101 on seizure frequency and developmental outcomes. The trial includes multiple parts with different age groups and study designs to understand its impact comprehensively. The study has three parts: Part 1A is an open-label dose-escalation phase for children aged 6 to less than 36 months, testing up to four dose levels of ETX101. Part 1B is an open-label phase for participants aged 48 months to less than 18 years, evaluating a single dose level. Part 2 is a randomized, double-blind, sham delayed-treatment control study for children aged 6 to less than 48 months, where participants are assigned in a 2:1 ratio to receive ETX101 or a sham procedure with delayed treatment. During participation, children will be monitored for changes in seizure frequency from before dosing to 52 weeks after treatment. Researchers will also assess cognitive and adaptive behavior development using standard scales like Bayley-4 and Vineland-3. Safety and efficacy will be closely observed through clinical evaluations, with follow-up lasting up to a year post-dosing to measure treatment outcomes and monitor health.

Researchers are evaluating the effects of zorevunersen, an investigational antisense oligonucleotide medicine, in children with Dravet syndrome, a rare epilepsy disorder caused by reduced Nav1.1 protein due to SCN1A gene mutations. This Phase 3, global, randomized, double-blind, sham-controlled study aims to assess the safety, tolerability, and potential to modify the disease by increasing Nav1.1 protein levels from the nonmutant gene copy. The study also measures changes in seizure frequency, behavior, cognition, clinical status, and quality of life. Participants are randomly assigned to one of two groups for Treatment Period 1, lasting about 52 weeks: either receive zorevunersen or undergo a sham procedure without drug administration. Zorevunersen is given by intrathecal injection at specific days and doses during this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen at defined intervals and doses. Patients may also join an open-label extension study if they meet criteria after the main study. Throughout the study, patients will be monitored regularly to assess seizure changes at weeks 28 and 52, as well as adaptive behavior using the Vineland-3 scale. Safety and tolerability are closely followed with standardized evaluations. The study lasts at least 84 weeks, including both treatment periods. Researchers aim to understand how zorevunersen may impact major motor seizures and overall functioning in children with Dravet syndrome.

Researchers are developing a multicenter registry to collect and share data on pediatric patients who have undergone deep brain stimulation (DBS) for movement disorders such as dystonia, epilepsy, Tourette syndrome, and mood disorders. The study aims to improve understanding of DBS safety and effectiveness in children, as current data are limited and individual centers often have too few cases for strong research. This registry will support large-scale analyses and help refine DBS as a treatment option for hyperkinetic movement disorders in the pediatric population. The study involves gathering both retrospective and prospective clinical data from multiple pediatric centers. The registry will collect information on surgical techniques, patient outcomes, implant sites, and long-term effects of DBS. This collaborative data-sharing approach enables comprehensive evaluation of which patients benefit most from DBS and how it impacts their quality of life over time. Participants include children aged 0 to 18 years who have already received or are scheduled to receive DBS for neurological movement disorders. Data will be collected over five years to monitor safety, efficacy, and quality of life outcomes. The study does not involve treatment administration but focuses on gathering and analyzing clinical information. Parental or legal guardian consent is required for prospective participation.

Dravet Syndrome (DS) is a severe neurodevelopmental disorder caused mostly by mutations in the SCN1A gene, leading to frequent, drug-resistant seizures, cognitive deficits, and a high risk of sudden unexpected death in epilepsy (SUDEP). SUDEP is a major cause of premature death in epilepsy patients and is linked to seizure frequency and brainstem dysfunction. This study aims to investigate serotonin (5HT) pathway alterations in the brainstem of adults with DS using PET and MRI imaging to better understand SUDEP mechanisms. The study will include 20 adult participants: 10 with confirmed Dravet Syndrome, 10 with drug-resistant focal epilepsy, and 10 healthy adults. All participants will undergo PET-MRI imaging with injection of the tracer [18F]-MPPF to assess the serotonin brainstem pathway. The imaging involves anatomical MRI scans followed by a 90-minute dynamic emission scan after tracer injection. Women of childbearing potential will have a pregnancy test before imaging. Participants will have one inclusion visit for eligibility review and clinical examination, followed by the PET-MRI scan scheduled within 2 to 8 weeks. Researchers will compare brainstem serotonin receptor binding between groups and relate imaging findings to central sleep apnea duration and brainstem volume. The study will measure the signal-to-noise ratio of 5-HT1A receptor binding in healthy controls and monitor safety throughout. Each participant's involvement lasts from 2 to 8 weeks.

Researchers are studying the effects of LP352 in children and adults with Dravet Syndrome, a condition characterized by seizures. This randomized, double-blind, placebo-controlled Phase 3 study aims to assess the efficacy, safety, and tolerability of LP352 in reducing seizures. The trial is sponsored by Longboard Pharmaceuticals and includes participants aged 2 to 65 years. Participants will be randomly assigned to receive either LP352 or a matching placebo, administered orally or through a feeding tube. The study includes a Screening phase, a Titration period where doses are gradually increased to the highest tolerated level, followed by a Maintenance period, then a Taper period to reduce the dose, and finally a Follow-Up phase. The entire study will last about 24 months. During the trial, participants will be closely monitored for seizure frequency and safety outcomes. Researchers will collect data on seizure counts, medication adherence, and any side effects. The primary measure is the change in the frequency of motor seizures compared to baseline over up to 15 weeks. Participants will also undergo regular visits for evaluation, and safety will be observed up to 21 weeks. The study aims to provide detailed information on how LP352 affects seizures and overall tolerability in this population.

Researchers are investigating epilepsy-dyskinesia syndromes, which are rare genetic diseases causing both movement disorders and epilepsy in children. This multinational retrospective survey, supported by the International Parkinson and Movement Disorder Society, aims to collect detailed clinical and molecular data to better understand these conditions. The study focuses on identifying patterns in disease features, progression, and genetic links to improve knowledge and support precision medicine. The study collects previously recorded data from multiple countries, harmonizing information on clinical features, disease progression, age of onset, genetic variants, and coexisting neurological conditions. By standardizing this data, the survey addresses challenges in rare disease research like small, dispersed patient groups and inconsistent protocols. The goal is to build a shared clinical database and analyze how movement and seizure disorders relate at both clinical and molecular levels. Participants are children aged 0 to 18 years with diagnosed movement disorders linked to specific genetic variants. The study reviews existing medical records and genetic information without new treatments or interventions. Researchers will assess the disease spectrum, how movement disorders affect quality of life, and the effectiveness of symptomatic treatments over one year. The study encourages international collaboration to advance understanding and improve care for these rare conditions.

Researchers are evaluating clemizole hydrochloride (EPX-100) as an additional treatment for children and adults with Dravet syndrome (DS), a rare form of epilepsy. This Phase 3 study is designed to assess the safety and effectiveness of clemizole hydrochloride compared to a placebo, focusing on reducing motor seizures. The study includes participants who have seizures not fully controlled by current anti-epileptic drugs and have a confirmed genetic mutation related to DS. Participants will first go through a 4-week observational period before being randomly assigned to receive either clemizole hydrochloride or a placebo as an oral solution during a 16-week double-blind period. After completing this phase, eligible participants can join an open-label extension where they receive clemizole hydrochloride for up to three years. This design allows researchers to monitor both short-term and longer-term effects of the treatment. During the study, participants will be closely monitored for changes in their motor seizure frequency using daily counts and clinical assessments. Researchers will also evaluate seizure-free days and overall seizure reduction, along with the use of rescue medications. Safety will be tracked throughout the study and the extension period, which may last up to approximately 172 weeks. Participants will have regular visits to assess their response and well-being throughout the trial.

Researchers are evaluating the efficacy of perampanel as an additional therapy for children and adolescents with pediatric epileptic syndrome and partial-onset seizures. The study aims to measure how well perampanel reduces seizure frequency, focusing on the 50% responder rate during the maintenance phase of the core study. This phase 2, open-label trial includes participants from 1 month to less than 18 years old with specific epilepsy diagnoses. The study includes a Core Study and two Extension Phases. The Core Study starts with a 4-week screening period, followed by a 23-week treatment period divided into a 10-week titration phase and a 13-week maintenance phase. Participants receive perampanel oral suspension or tablets once daily for up to 56 weeks. Those completing the Core Study may join Extension Phase A, which has a 33-week treatment period and a 4-week follow-up. Extension Phase B is available for participants in areas without commercial perampanel or extended access programs, continuing treatment as deemed beneficial by investigators. Throughout the study, participants will undergo regular assessments including seizure frequency monitoring, cognitive and behavioral evaluations, growth and development measurements, and safety checks such as vital signs, laboratory tests, and electroencephalograms. Researchers will track responders who achieve seizure reductions and evaluate overall clinical impressions and drug effects. Participation may last up to about 60 weeks, including all phases and follow-up periods, with careful monitoring of adverse events and treatment impact.

Researchers are evaluating the use of Pulsed Low-Intensity Focused Ultrasound (PLIFU) to reduce or suppress seizure activity in adults experiencing non-convulsive or focal motor status epilepticus (SE) who have not responded to standard treatments. The study focuses on brain regions that generate or control seizures, aiming to assess the effects of this non-invasive brain stimulation in a hospital setting. Participants will receive up to two sessions of PLIFU treatment in the Intensive Care Unit. Each session lasts 10 minutes and uses a custom device that delivers ultrasound to specific brain areas without damaging tissue. Treatments will be given after anti-seizure medications have been administered, and the ultrasound is applied using safe, non-thermal settings. During the study, participants will be monitored continuously with surface EEG to measure epileptic brain activity before, during, and after PLIFU treatment. Researchers will observe changes in seizure activity and follow participants throughout their hospital stay. The main outcome is the change in epileptiform activity measured by EEG at baseline and 10 minutes after treatment. The study aims to gather preliminary data to support future research.

Researchers are evaluating the safety and tolerability of ION337 in children with Dravet syndrome (DS) aged 2 to 12 years. Dravet syndrome is a severe form of epilepsy, and this open-label study aims to understand how well participants tolerate this investigational treatment and monitor its safety over time. The study is divided into two parts. In Part 1, participants receive a single intrathecal bolus injection of ION337 and are observed for 6 months in a single ascending dose phase. Participants who complete Part 1 may enter Part 2, where they receive multiple doses of ION337 over 24 months in a multiple ascending dose phase, followed by a 7-month safety follow-up period. All doses are administered intrathecally. Participants will be closely monitored throughout the study with assessments including physical and neurological exams, vital signs, ECGs, laboratory tests, and tracking of treatment-emergent adverse events. Researchers will also measure seizure frequency and analyze drug levels in blood and cerebrospinal fluid. The total study duration for participants can be up to 31 months, including treatment and follow-up.