Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy

Phase 2

Active, not recruiting

• Conditions: Lennox-Gastaut Syndrome; Dravet Syndrome; Developmental and Epileptic Encephalopathy
• Interventions: Drug: LP352, bexicaserin

• Registration Number: NCT05626634
• Lead Sponsor: Longboard Pharmaceuticals

Brief Summary

The objective of this study is to assess the long-term safety, tolerability, and efficacy of adjunctive therapy of LP352 in subjects with developmental and epileptic encephalopathies who completed participation in Study LP352-201.

Detailed Description

This Phase 2, multicenter, open-label, multiple-dose extension clinical study is designed to evaluate long-term safety of LP352 in subjects with developmental and epileptic encephalopathy who completed Study LP352-201.

The study consists of a Screening Period (Day -1) and a 50-week open-label Treatment Period that includes a 15-day Up-titration Period (during which time subjects will titrate up to their highest tolerated doses) and an open-label Maintenance Period (48 weeks). The Treatment Period will be followed by a Down-titration/Taper Period (up to 15 days) and Follow-up Period (14 days after completion of down-titration). The starting dose of up-titration will be 6 mg TID. The target final maintenance doses are 6 mg TID, 9 mg TID, and 12 mg TID after a 15-day up-titration period, if tolerated.

Study Timeline

• Study Start: 2022-11-08
• Study First Submitted: 2022-11-15
• Study First Submitted QC: 2022-11-15
• Study First Posted: 2022-11-25
• Status Verified: 2024-12
• Primary Completion: 2024-12
• Study Completion: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Male or non-pregnant, non-lactating female, age 12 to 65 years who have satisfactorily completed study LP352-201
2. Diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or other developmental and epileptic encephalopathy
3. The patient/parent/caregiver is able and willing to attend study visits, complete the diary and take study drug as instructed

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Exclusion Criteria

1. Had an SAE in Study LP352-201 that was definitely, probably, or possibly related to exposure to study drug
2. Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, pulmonary arterial hypertension or abnormal blood pressure
3. Has glaucoma, renal impairment, liver disease or any other medical condition that would affect study participation or pose a risk to the subject
4. Current or recent history of moderate or severe depression, anorexia nervosa, bulimia or at risk of suicidal behavior
5. Currently taking anorectic agents, monoamine oxidase inhibitors; serotonin agonists or antagonists including fenfluramine, atomoxetine, vortioxetine, or other medications for weight loss
6. Positive test result on the drug screen, except tetrahydrocannabinol (THC) for patients taking prescribed cannabidiol

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LP352, bexicaserin	LP352, bexicaserin	Subjects will be titrated up to highest tolerated dose of LP352 during a 15-day period, followed by a 48-week maintenance period and a 15-day taper/down titration period.

Primary Outcome Measures

Name	Time	Method
Treatment-emergent Adverse Events	Baseline up to Week 52	Incidence and severity of treatment-emergent adverse events, including serious adverse events and adverse events leading to study discontinuation and clinically significant changes in vital signs, physical examination endpoints, clinical safety laboratory values and ECGs
Patient Health Questionnaire-9 Total Score and Question 9 Score	Baseline up to Week 52	Severity Rating Scale: 0 - 27; higher scores indicate greater severity of depressive disorder
Columbia-Suicide Severity Rating Scale (C-SSRS) Response	Baseline up to Week 52	Type of Suicidal Ideation, Intensity (1 - 5, with 5 being most severe), Suicidal Behavior

Secondary Outcome Measures

Name	Time	Method
Percent Change from Baseline in Observed Countable Motor Seizure Frequency During the Treatment Period	Baseline to Week 50	Baseline Used for Seizure Frequency = Baseline from Study LP352-201 and Baseline from Study LP352-202
Percent of Subjects with Countable Motor Seizure-free Days During the Treatment Period	Baseline to Week 50
Proportion of Subjects with > 50% Reduction in Total Seizures During the Treatment Period	Baseline to Week 50
Percent Reduction in Individual Seizure Type During the Treatment Period	Baseline to Week 50
Proportion of Subjects Requiring Rescue Medication During the Treatment Period	Baseline to Week 50
Percent Change from Baseline in the Number of Episodes of Status Epilepticus During the Treatment Period	Baseline to Week 50
LGS: Percentage Change from Baseline in the Frequency of Observed Drop Seizures Over the Treatment Period	Baseline to Week 50
Percentage Change from Baseline in Non-motor and Difficult to Count Seizures	Baseline to Week 50

Trial Locations

Locations (28)

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

Northeast Regional Epilepsy Group; 🇺🇸 Staten Island, New York, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia

Queensland Children's Hospital; 🇦🇺 South Brisbane, Queensland, Australia

University of South Florida; 🇺🇸 Tampa, Florida, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Mid-Atlantic Epilepsy and Sleep Center; 🇺🇸 Bethesda, Maryland, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Providence Neurological Specialties-East; 🇺🇸 Portland, Oregon, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Northwest Florida Clinical Research Group; 🇺🇸 Gulf Breeze, Florida, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Spectrum Health; 🇺🇸 Grand Rapids, Michigan, United States

Northwell Health; 🇺🇸 New York, New York, United States

Austin Epilepsy Care Center; 🇺🇸 Austin, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of Washington Valley Medical Center; 🇺🇸 Renton, Washington, United States

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Rancho Los Amigos National Rehabilitation Center (RLANRC); 🇺🇸 Downey, California, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Boston Children's Health Physicians LLP; 🇺🇸 Hawthorne, New York, United States

OnSite Clinical Solutions LLC; 🇺🇸 Charlotte, North Carolina, United States

Advent Health Orlando; 🇺🇸 Orlando, Florida, United States

Research Institute of Orlando; 🇺🇸 Orlando, Florida, United States

Hawaii Pacific Neuroscience; 🇺🇸 Honolulu, Hawaii, United States

Wake Forest University School of Medicine; 🇺🇸 Winston-Salem, North Carolina, United States

Child Neurology Consultants of Austin; 🇺🇸 Austin, Texas, United States