Developmental and Epileptic Encephalopathy 50

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 investigating the safety and effectiveness of elsunersen in children with early onset SCN2A Developmental and Epileptic Encephalopathy (DEE), a rare neurological condition characterized by frequent seizures starting before three months of age. This phase 3 clinical trial focuses on pediatric participants who have a specific genetic mutation called Gain of Function SCN2A variant confirmed by genetic testing. The study aims to see how elsunersen affects seizure frequency and other related measures over 24 weeks. Participants will receive open-label treatment with elsunersen administered intrathecally every four weeks for 24 weeks. Two dosing options are studied: 1 mg and 0.5 mg of elsunersen. The trial has multiple cohorts, each receiving the open-label treatment during the experimental period. There is no placebo group, and all participants will be monitored closely throughout the study. During the trial, participants will be evaluated on seizure frequency, clinical global impression scales, sleep assessments, and other efficacy measures at various time points over 24 weeks. Safety and tolerability of elsunersen will also be assessed throughout this period. The total participation duration covers the 24-week treatment and observation period, with ongoing evaluations to understand the drug's effects in this pediatric population.

Researchers are studying PRAX-222 in children aged 2 to 18 years who have early onset SCN2A developmental and epileptic encephalopathy (DEE), a rare form of epilepsy that begins before 3 months of age. This trial aims to learn about the safety and effects of multiple doses of PRAX-222 in this pediatric population. The study is sponsored by Praxis Precision Medicines and includes phases to assess safety and efficacy. Participants will receive different doses of PRAX-222 or a placebo in a randomized, double-blind design. The study includes an initial dose escalation phase with ascending doses, optional further dose escalations, fixed-dose treatment phases, and open-label treatment periods where all participants may receive PRAX-222. Placebo procedures are included to compare responses. The dosing schedule varies across these treatment phases. Throughout the trial, children will be monitored for treatment-emergent adverse events and seizure frequency at various timepoints up to 92 weeks. Assessments include seizure counts, clinical global impression scores, developmental milestones, EEG measures, behavior scales, quality of life, and sleep evaluations. This comprehensive monitoring helps researchers understand the treatment's safety and impact. Participation may last up to nearly two years depending on study phases.

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 conducting a Phase Ib/II, first-in-human, multicenter, open-label study to assess the safety, tolerability, and how the body processes and responds to the drug S230815 in children aged 2 to 12 years with Developmental Epileptic Encephalopathy caused by a genetic variant in the KCNT1 gene. To join, participants must have a confirmed diagnosis through genetic testing. The study is sponsored by Institut de Recherches Internationales Servier and focuses on this rare pediatric epilepsy condition. The study includes a screening period followed by two parts. Part 1 tests multiple increasing doses of S230815 given as a solution for injection. Part 2 is a long-term treatment extension where participants continue receiving the same dose for up to 72 weeks after completing Part 1. Participants will move seamlessly from Part 1 to Part 2, staying in their assigned dose group. Participants will be closely monitored throughout, with assessments including daily seizure logs and periodic 24-hour video EEGs to record seizure frequency. Researchers will also evaluate drug levels in the cerebrospinal fluid and blood plasma. Safety is carefully tracked by recording any adverse events through the study, which can last up to 116 weeks. The study aims to understand how safe and tolerable S230815 is and how it affects seizures in this patient group.

Researchers are studying adolescents and young adults with autism spectrum disorder (ASD), a condition marked by difficulties in communication, social skills, and repetitive behaviors. The study aims to understand how a brain stimulation technique called transcranial direct current stimulation (tDCS) might reduce symptoms like anxiety and impulsivity. The research also seeks to use brain activity data and clinical information to predict who will respond well to this treatment. Participants will receive active tDCS for 10 sessions over two weeks, one session per day on working days. During each 20-minute session, they will perform exercises designed to improve processing speed and executive function while receiving brain stimulation. After treatment, participants will be classified as responders or non-responders based on improvements in social responsiveness scores. Throughout the study, participants will undergo various assessments including behavioral scales, cognitive tests, and neurophysiological measurements at the start and after the treatment period. Researchers will track changes in social communication, repetitive behaviors, and brain function. This will help determine the effects of tDCS and identify characteristics that predict treatment response, with the total study duration extending up to the final follow-up in 2026.

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.

Researchers are studying STXBP1-related disorders (STXBP1-RD), which are rare genetic neurodevelopmental conditions causing developmental delays, intellectual disability, seizures, behavioral problems, and movement disorders. These disorders vary widely in severity and significantly affect patients' and caregivers' quality of life. Currently, there is no cure, and treatments mainly focus on controlling symptoms. This European collaborative study aims to better understand the natural history, identify disease modifiers, relevant clinical endpoints, and outcome measures to prepare for future clinical trials of new precision therapies. The study involves a large-scale, pan-European natural history study composed of two phases: a 12-month pilot natural history study (pNHS) and a 4-year extension natural history study (eNHS). Researchers will collect both retrospective and prospective data on demographics, genetics, and clinical features from patients with STXBP1-RD. The pilot phase will assess the sensitivity of outcome measures to detect differences in impairment and changes over time, as well as the burden of study participation for patients and caregivers. Participants will be followed over different life stages including infancy, childhood, adolescence, and adulthood. Assessments include clinical evaluations and patient and caregiver input to capture the disease's impact and unmet needs. The primary outcome measure is changes in clinical assessment percentiles over 12 months. This comprehensive data collection will support the development of relevant endpoints and biomarkers for future clinical trials, with the overall participation lasting up to several years depending on the study phase.

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.