Developmental and Epileptic Encephalopathy 50

Researchers are investigating ETX101, a gene therapy delivered via an adeno-associated viral vector, in infants and children diagnosed with SCN1A-positive Dravet syndrome. The study includes multiple age groups ranging from 6 months to under 18 years and aims to assess the safety and effects of ETX101. It is designed as a Phase 12, multicenter trial with different parts evaluating dose levels and treatment impact using a randomized, controlled approach in later stages. The study is divided into parts Part 1A uses an open-label, dose-escalation design to test up to four doses of ETX101 in participants aged 6 to under 36 months. Part 1B is open-label and tests a single dose in participants aged 48 months to under 18 years. Part 2 is a double-blind, randomized, sham delayed-treatment control study involving participants aged 6 to under 48 months, where participants receive either ETX101 or a sham procedure with delayed treatment. This part includes two cohorts and lasts up to 52 weeks. Participants will be closely monitored through the study with assessments of seizure frequency, cognitive and adaptive behavior changes using tools like the Bayley-4 and Vineland-3 scales, and clinical global impressions over 52 weeks. Safety and effectiveness are evaluated by comparing seizure counts before and after dosing. The study includes various cognitive and behavioral outcome measures and follows participants from dosing up to one year for treatment effects and safety observations.

This clinical trial evaluates the efficacy and safety of elsunersen in children with early-onset SCN2A Developmental and Epileptic Encephalopathy, a condition characterized by seizures beginning before 3 months of age. The study focuses on pediatric participants confirmed to have a gain of function SCN2A genetic variant, aiming to understand how elsunersen impacts seizure frequency and related symptoms. The trial is sponsored by Praxis Precision Medicines and is conducted at multiple centers. Participants receive intrathecal doses of elsunersen every 4 weeks for a total of 24 weeks. Two dosing levels, 1mg and 0.5mg, are being studied in an open-label design across three cohorts. All participants receive the study drug without a placebo comparison, and treatment effects on seizures and other clinical assessments are monitored throughout the treatment period. During the 24-week treatment, participants undergo regular evaluations to assess seizure frequency, clinical global impression of severity and improvement, and sleep quality among other outcomes. Safety and tolerability are also closely monitored. The trial includes baseline observation periods and follow-up assessments to track changes over time, providing a comprehensive view of elsunersens impact in this pediatric population.

Researchers are evaluating zorevunersen, an investigational antisense oligonucleotide drug, in children with Dravet syndrome, a rare and severe form of epilepsy. This Phase 3, global, multicenter, randomized, double-blind, sham-controlled study aims to assess the efficacy, safety, and tolerability of zorevunersen by measuring changes in major motor seizure frequency and other important aspects such as behavior, cognition, clinical status, and quality of life. Participants will be randomly assigned to receive either zorevunersen or a sham procedure during Treatment Period 1, which lasts about 52 weeks. Zorevunersen is given by intrathecal injection at specific doses and intervals throughout this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen for additional dosing over several months. Patients who complete the study may have the chance to join an open-label extension to continue receiving the drug. During the study, participants will undergo regular assessments including seizure monitoring, behavioral and cognitive evaluations, and health-related quality of life measurements. The primary outcome is the change in major motor seizure frequency at Week 28, with secondary outcomes assessed at Week 52. Safety and tolerability are also closely monitored. Overall participation lasts through both treatment periods and possible extension, with detailed follow-up to evaluate the drugs potential for disease modification.

Researchers are studying pediatric participants aged 2 to 12 years with Developmental Epileptic Encephalopathy caused by a genetic variant in the KCNT1 gene. This Phase IbII, first-in-human, multicenter, open-label study aims to assess the safety, tolerability, and how the investigational drug S230815 behaves in the body and affects the disease. The trial is sponsored by Institut de Recherches Internationales Servier and includes a screening period followed by two treatment parts. Participants will receive multiple ascending doses of S230815 administered intrathecally during Part 1 of the study. Those who complete Part 1 may continue into Part 2, a long-term treatment extension lasting up to 72 weeks, continuing with the same dose cohort as in Part 1. The treatment is given as a solution for injection, and dosing is designed to evaluate safety and drug effects over time. Throughout the study, participants will be closely monitored for adverse events and drug levels in cerebrospinal fluid and plasma. Seizure frequency will be tracked using daily logs and periodic 24-hour video EEG assessments. Researchers will also record the use of rescue medications. The total participation may last up to 116 weeks, including the screening, treatment, and follow-up visits, ensuring thorough evaluation of the drugs impact and safety profile.

Researchers are investigating the use of transcranial direct current stimulation tDCS combined with cognitive training to address symptoms in adolescents with autism spectrum disorder ASD. ASD is characterized by challenges in communication, social skills, repetitive behaviors, and emotional distress triggered by environmental changes. This study aims to determine if baseline resting-state EEG and clinical data can predict which individuals respond to tDCS treatment, helping to improve intervention strategies. Participants will receive active tDCS over 10 sessions during two weeks, with one session per day on consecutive working days. Each session includes 20 minutes of tDCS combined with an online cognitive training program consisting of five exercises targeting information processing speed and executive function. After treatment, participants will be classified as responders or non-responders based on changes in social responsiveness scores. During the study, assessments will measure changes in social communication and repetitive behaviors using the Social Responsiveness Scale, cognitive function through various CANTAB tests, and neurophysiological measures at the start and immediately after the intervention. Researchers will monitor behavioral changes and executive function outcomes to evaluate the impact of the combined treatment over the study period ending 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 diseases 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 participants involvement lasts from 2 to 8 weeks.

Researchers are evaluating the drug LP352 in a phase 3, randomized, double-blind, placebo-controlled trial to study its effects on seizures in children and adults with Dravet Syndrome DS. This serious condition involves various seizure types with onset between 1 and 20 months of age. The study aims to test the efficacy, safety, and tolerability of LP352 compared to placebo over a total duration of about 24 months. Participants will be randomly assigned to receive either LP352 or a matching placebo. LP352 or placebo will be given orally or through a feeding tube. The study includes three main phases a Screening phase, a Titration period where doses are gradually increased to the highest tolerated level, and a Maintenance period to assess ongoing treatment effects. Afterward, participants will undergo a Taper period to reduce dosing and a Follow-Up phase for observation. During the study, participants will be monitored for seizure frequency changes, safety, and tolerability. Researchers will track countable motor seizures and measure percent change compared to baseline over up to 15 weeks. Participants or caregivers will complete seizure diaries, and stable antiseizure medication use is required. Safety evaluations will continue up to 21 weeks, with study visits scheduled throughout these phases. Total participation lasts approximately two years.

Researchers are evaluating the effectiveness and safety of L-fucose supplementation in adults diagnosed with GLUT1 deficiency syndrome GLUT1DS, a rare condition affecting glucose transport. This Phase II study uses a randomized, double-blind, placebo-controlled, cross-over design to compare L-fucose treatment to placebo over a 24-week period. The goal is to explore potential improvements in neurological symptoms and assess safety in this population. Participants will receive either L-fucose or placebo for 12 weeks, then switch to the other treatment for another 12 weeks. L-fucose is given orally at a dose of 500 mgkg up to a maximum of 10 grams three times daily. The placebo is a micro-cellulose powder with Stevia to match the taste and dosing schedule. This cross-over approach allows each participant to experience both treatments during the study. During the study, participants undergo regular assessments including neurological scales such as the Scale for the Assessment and Rating of Ataxia SARA and International Cooperative Ataxia Rating Scale ICARS. Safety labs monitor blood counts, liver and kidney function, electrolytes, and other parameters. Researchers also track adverse events reported by participants. Additional measures include evaluations of speech difficulties, migraine frequency, exercise-induced dystonia, seizures, quality of life, and patient-reported health outcomes. The total study duration per participant is 24 weeks, with careful monitoring throughout.