Evaluation of Long-Term Safety and Efficacy of Bexicaserin (LP352) in Pediatric and Adult Patients with Developmental and Epileptic Encephalopathy

The primary objective of this Phase 3, open-label study is to evaluate the **safety** and **tolerability** of bexicaserin (LP352) in individuals with **Developmental and Epileptic Encephalopathies (DEEs)**. This is clinically relevant as it aims to ensure that the treatment is safe for long-term use in both children and adults, which is crucial for managing a chronic condition like DEE.

Secondary objectives include:

• To evaluate the **efficacy** of bexicaserin (LP352) in DEE, which is important for determining the therapeutic potential of the drug in reducing seizure frequency and improving patient outcomes.

The clinical trial involves a total of **135 participants** diagnosed with **Developmental and Epileptic Encephalopathies (DEEs)**, including Dravet Syndrome (DS) and Lennox-Gastaut Syndrome (LGS). The study population comprises both male and female subjects, with an age range that includes children, adolescents, and adults. Participants were selected based on their satisfactory completion of previous studies (LP352-301 or LP352-302) and the potential benefit from continued administration of the investigational drug, bexicaserin (LP352). The trial includes a vulnerable population, necessitating the presence of a reliable and consistent parent, legal guardian, or caregiver throughout the study. Participants are required to comply with study procedures, including the completion of diaries, and must provide informed consent or assent as per local regulations. The trial does not specify particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants are capable of adhering to the study requirements, with the involvement of a legal representative when necessary.

The clinical trial is designed to evaluate the **safety** and tolerability of **bexicaserin** (LP352) in individuals with **Developmental and Epileptic Encephalopathies** (DEEs). This is a Phase 3, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial is expected to commence recruitment on September 1, 2025, and conclude by November 30, 2027. Participants who have satisfactorily completed previous studies (LP352-301 or LP352-302) and meet the inclusion criteria will be eligible for this study. The trial will involve the administration of **bexicaserin** as an oral solution, with a maximum daily dose of 36 mg and a total dose not exceeding 14,364 mg over a treatment period of 57 days.

Study visits are structured to ensure comprehensive monitoring and data collection. The initial visit will serve as a screening to confirm eligibility based on the inclusion criteria, such as a confirmed diagnosis of DEE and the ability to comply with study requirements. Subsequent visits will be scheduled to assess primary endpoints, including the incidence and severity of treatment-emergent adverse events (TEAEs), safety laboratory parameters, and vital signs. Secondary endpoints will focus on the frequency and percentage change in countable motor seizures, as recorded in a seizure eDiary. The end-of-study visit will evaluate the overall safety and efficacy outcomes, including physical examination findings and growth parameters.

Participant involvement is expected to last for the duration of the treatment period, with regular follow-up visits to monitor progress and any adverse effects. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or the participant's inability to comply with the study protocol. The trial aims to provide valuable insights into the long-term safety and efficacy of **bexicaserin** in treating seizures associated with DEEs, contributing to the development of effective therapeutic strategies for this condition.

The clinical trial involves the administration of **Bexicaserin**, an investigational medication, in the form of an **oral solution**. The active substance in this formulation 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 14,364 mg over a treatment period of up to 57 days. The study aims to evaluate the safety and tolerability of bexicaserin in individuals with developmental and epileptic encephalopathy (DEE).

In addition to the experimental treatment, a **placebo** oral solution is utilized as a comparator in the study. The placebo is designed to mimic the appearance and administration route of the active medication, ensuring blinding and maintaining the integrity of the trial. The placebo does not contain the active substance, bexicaserin hydrochloride, and is used to assess the efficacy and safety of the investigational drug by providing a baseline for comparison.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. This monitoring is crucial for maintaining the validity of the study results and ensuring participant safety. The trial is conducted under strict regulatory guidelines to evaluate the long-term safety and efficacy of LP352 in treating seizures associated with DEE.

The efficacy of the investigational product, **bexicaserin**, in the treatment of seizures in children and adults with Developmental and Epileptic Encephalopathy (DEE) will be assessed through several secondary endpoints. These endpoints include the frequency percent change in countable motor seizures during the treatment phase, which is calculated as a 28-day average compared to the baseline 28-day average, as assessed by a seizure eDiary. Additionally, the 50% responder rate, defined as the percentage of participants experiencing a 50% or greater reduction in countable motor seizures during the treatment phase compared to baseline, will also be evaluated using the seizure eDiary. Furthermore, the frequency percent change in countable motor seizures during the maintenance phase, again compared to the baseline 28-day average, will be assessed.