Efficacy and Safety of Bexicaserin in Seizure Management for Pediatric and Adult Dravet Syndrome: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this Phase 3, randomized, double-blind, placebo-controlled, multicenter study is to evaluate the **efficacy** of LP352 in Dravet Syndrome, specifically by assessing the reduction in countable motor seizures. This is clinically relevant as Dravet Syndrome is a severe form of epilepsy characterized by frequent and prolonged seizures, and effective management of these seizures is crucial for improving patient outcomes.

Secondary objectives include:

• Evaluating the **safety** and tolerability of LP352 in individuals with Dravet Syndrome, which is essential to ensure that the treatment does not pose undue risk to patients.
• Assessing the overall **efficacy** of LP352 in managing Dravet Syndrome, providing a broader understanding of its potential benefits beyond seizure reduction.

The clinical trial involves a total of **73 participants** diagnosed with **Dravet Syndrome**, a severe form of epilepsy. The study population includes both male and female subjects, ranging in age from 2 to 65 years. Participants were selected based on specific criteria, including a confirmed diagnosis of Dravet Syndrome according to the International League Against Epilepsy definition, and a history of certain seizure types. All participants have demonstrated an average of at least four countable motor seizures per month for the three months prior to screening. They have been on a stable dose of 1 to 4 anti-seizure medications for at least four weeks before the trial. The trial population includes a vulnerable group, and participants are required to provide written informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy, safety, and tolerability of LP352 in the treatment of seizures in children and adults with **Dravet Syndrome**. The trial will involve participants aged 2 to 65 years who meet specific inclusion criteria, including a confirmed diagnosis of Dravet Syndrome and a history of countable motor seizures. The study will be conducted over an estimated period, with recruitment starting in May 2025 and concluding by May 2026.

Participants will be randomly assigned to receive either the investigational product, **Bexicaserin**, or a placebo, both administered as an oral solution. The trial will consist of several key phases, including a screening visit to confirm eligibility, followed by a treatment period where participants will receive the study medication. The primary endpoint is the frequency percent change in countable motor seizures during the maintenance phase compared to baseline. Secondary endpoints include the incidence and severity of treatment-emergent adverse events, safety laboratory parameters, and other health assessments.

Study visits will be scheduled at regular intervals to monitor participants' health and response to treatment. These visits will include physical examinations, vital signs assessments, and the collection of safety data. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the overall impact of the treatment. Participants are expected to be involved in the study for a maximum treatment period of 17 weeks, with conditions for early termination including the occurrence of serious adverse events or non-compliance with study protocols.

The clinical trial involves the administration of **Bexicaserin**, an investigational medication, formulated as an oral solution. The active substance in this formulation is **bexicaserin hydrochloride**, a chemical compound. The pharmaceutical form is an oral solution, which can be administered orally, via a nasogastric tube, or through a percutaneous endoscopic gastrostomy tube. The maximum daily dose of Bexicaserin is 36 mg, with a total maximum dose of 4284 mg over a treatment period of 17 weeks. The medication is provided by Longboard Pharmaceuticals, Inc. and is identified by the sponsor product code LP352. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.

The study also includes a placebo control, identified as LP352 (bexicaserin) Placebo Oral Solution. This placebo is designed to match the experimental medication in appearance and administration route, ensuring the double-blind nature of the trial. The placebo is administered in the same manner as Bexicaserin, either orally, via a nasogastric tube, or through a percutaneous endoscopic gastrostomy tube, to maintain consistency in the treatment protocol. The use of a placebo allows for the assessment of the efficacy and safety of Bexicaserin by providing a comparator against which the effects of the active medication can be measured.

The efficacy of LP352 in the treatment of seizures in children and adults with **Dravet Syndrome** will be assessed through a Phase 3, randomized, double-blind, placebo-controlled, multicenter study. The primary endpoint for evaluating efficacy is the frequency percent change in countable motor seizures during the maintenance phase compared to baseline. This will involve monitoring specific seizure types, including generalized tonic-clonic, tonic (bilateral), clonic (bilateral), atonic (bilateral) with truncal/leg involvement, focal motor (including hemiclonic), and focal to bilateral tonic-clonic seizures.

Secondary endpoints will include the incidence and severity of Treatment Emergent Adverse Events (TEAEs), including Serious Adverse Events (SAEs) and Adverse Events (AEs) leading to discontinuation. Additional assessments will involve safety laboratory parameters, physical examination findings, vital signs, growth parameters (height and weight), 12-lead Electrocardiogram (ECGs), Columbia-Suicide Severity Rating Scale (C-SSRS) responses, and Patient Health Questionnaire-9 (PHQ-9) total score and Question 9 score. The 50% responder rate, defined as the percentage of participants with a ≥50% reduction in countable motor seizures during treatment compared to baseline, will also be evaluated.