Efficacy and Safety of Bexicaserin Hydrochloride in Developmental and Epileptic Encephalopathies: 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 the treatment of **Developmental and Epileptic Encephalopathies (DEE)**, specifically by assessing the reduction in countable motor seizures. This is clinically relevant as DEE is characterized by severe seizures that can significantly impact the quality of life and development in affected individuals. The study aims to determine whether LP352 can effectively reduce the frequency of these seizures, thereby potentially improving patient outcomes.

Secondary objectives include evaluating the overall efficacy of LP352 in DEE, which encompasses a broader assessment of its impact on seizure control and other related symptoms. This comprehensive evaluation is crucial for understanding the full therapeutic potential of LP352 in managing DEE.

The clinical trial involves a total of **100 participants** diagnosed with **Developmental and Epileptic Encephalopathies (DEE)**, including those with Lennox-Gastaut Syndrome (LGS). The study population comprises both male and female subjects, with an age range that includes children and adolescents. Participants were selected based on specific criteria, including the onset of seizures at a young age, a history of multiple seizure types, and developmental plateauing or regression. The trial includes individuals who have been on a stable dose of 1 to 4 antiseizure medications for at least four weeks prior to screening. Participants are required to have a current occurrence of countable motor seizures, averaging at least four per month in the three months preceding the screening. The study population is considered vulnerable, and informed consent is obtained from participants or their legal representatives, with assent from the participants as per local regulations. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy, safety, and tolerability of LP352 in the treatment of seizures in children and adults with **Developmental and Epileptic Encephalopathies (DEE)**. The trial aims to assess the efficacy of LP352 by measuring the frequency percent change in countable motor seizures during the maintenance phase compared to baseline. The study is expected to commence recruitment on June 30, 2025, and conclude by May 31, 2026, with an estimated duration of 17 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as a history of multiple seizure types and a stable dose of 1 to 4 antiseizure medications. Following successful screening, participants will be randomized to receive either the investigational product, **Bexicaserin**, or a placebo, both administered as an oral solution. The trial includes a baseline period, a treatment phase, and a maintenance phase, with regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted.

Participant involvement is expected to last for the entire duration of the trial, approximately 17 months, unless early termination is warranted. Conditions that may lead to early withdrawal include adverse events, non-compliance with study procedures, or withdrawal of consent. The primary endpoint focuses on the frequency percent change in countable motor seizures, while secondary endpoints include the 50% responder rate and frequency percent change during the treatment phase compared to baseline. The trial is not classified as a low-intervention study, as it involves a non-authorized investigational medicinal product.

The clinical trial involves the administration of **Bexicaserin**, an experimental medication formulated as an **oral solution**. The active substance in this medication is **bexicaserin hydrochloride**, a chemical compound developed by Longboard Pharmaceuticals, Inc. The medication is administered via oral, nasogastric tube, or percutaneous endoscopic gastrostomy tube use. The maximum daily dose is 36 mg, with a total maximum dose of 4284 mg over a treatment period of 17 days. The dosing schedule is designed to ensure optimal efficacy while monitoring for safety and tolerability in participants with developmental and epileptic encephalopathies. Compliance with the dosing regimen is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental treatment, a **placebo** oral solution is used as a comparator in this double-blind, placebo-controlled study. The placebo is designed to match the experimental medication in appearance and administration route, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This approach is critical for maintaining the integrity of the study and accurately assessing the efficacy and safety of Bexicaserin. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the true effects of the experimental medication.

The efficacy of the investigational medicinal product, **Bexicaserin**, will be assessed in 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. Secondary endpoints include the 50% responder rate, defined as the percentage of participants experiencing a ≥50% reduction in countable motor seizures during the Maintenance phase compared to Baseline, as well as the frequency percent change in countable motor seizures during the Treatment phase compared to Baseline.

Participants will be monitored for countable motor seizures, which include generalized tonic-clonic, tonic (bilateral), clonic (bilateral), atonic (bilateral) with truncal/leg involvement, focal motor (including hemiclonic), and focal to bilateral tonic-clonic seizures. The data collection will involve the use of participant diaries to record seizure occurrences, ensuring compliance with the study protocol. The analysis will focus on comparing seizure frequency changes from Baseline to the Maintenance and Treatment phases to determine the efficacy of **Bexicaserin** in reducing seizure frequency in individuals with Developmental and Epileptic Encephalopathies.