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

Dravet Syndrome Clinical Trial

Official title:

A Phase 2, Multicenter, Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy Who Completed Study LP352-201 and Are Candidates for Continuous Treatment for Up to 52 Weeks

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05626634
• Other study ID #: LP352-202
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 8, 2022
• Est. completion date: October 2024

Study information

• Verified date: May 2024
• Source: Longboard Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Brain Diseases
• Dravet Syndrome
• Epilepsies, Myoclonic
• Epilepsy
• Lennox Gastaut Syndrome
• Lennox-Gastaut Syndrome
• Syndrome

Intervention

Drug:
• LP352, bexicaserin
LP352 6 mg, 9 mg or 12 mg administered three times daily, orally or through G-tube

Locations

Country	Name	City	State
Australia	Austin Health	Heidelberg	Victoria
Australia	Alfred Health	Melbourne	Victoria
Australia	Queensland Children's Hospital	South Brisbane	Queensland
United States	Austin Epilepsy Care Center	Austin	Texas
United States	Child Neurology Consultants of Austin	Austin	Texas
United States	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland
United States	OnSite Clinical Solutions LLC	Charlotte	North Carolina
United States	Northwestern University Feinberg School of Medicine	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Rancho Los Amigos National Rehabilitation Center (RLANRC)	Downey	California
United States	Spectrum Health	Grand Rapids	Michigan
United States	Northwest Florida Clinical Research Group	Gulf Breeze	Florida
United States	Boston Children's Health Physicians LLP	Hawthorne	New York
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Miami	Miami	Florida
United States	Northwell Health	New York	New York
United States	Advent Health Orlando	Orlando	Florida
United States	Research Institute of Orlando	Orlando	Florida
United States	Providence Neurological Specialties-East	Portland	Oregon
United States	University of Washington Valley Medical Center	Renton	Washington
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Northeast Regional Epilepsy Group	Staten Island	New York
United States	University of South Florida	Tampa	Florida
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Longboard Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-emergent Adverse Events	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	Baseline up to Week 52
Primary	Columbia-Suicide Severity Rating Scale (C-SSRS) Response	Type of Suicidal Ideation, Intensity (1 - 5, with 5 being most severe), Suicidal Behavior	Baseline up to Week 52
Primary	Patient Health Questionnaire-9 Total Score and Question 9 Score	Severity Rating Scale: 0 - 27; higher scores indicate greater severity of depressive disorder	Baseline up to Week 52
Secondary	Percent Change from Baseline in Observed Countable Motor Seizure Frequency During the Treatment Period	Baseline Used for Seizure Frequency = Baseline from Study LP352-201 and Baseline from Study LP352-202	Baseline to Week 50
Secondary	Proportion of Subjects with > 50% Reduction in Total Seizures During the Treatment Period		Baseline to Week 50
Secondary	Percent Reduction in Individual Seizure Type During the Treatment Period		Baseline to Week 50
Secondary	Proportion of Subjects Requiring Rescue Medication During the Treatment Period		Baseline to Week 50
Secondary	Percent Change from Baseline in the Number of Episodes of Status Epilepticus During the Treatment Period		Baseline to Week 50
Secondary	Percent of Subjects with Countable Motor Seizure-free Days During the Treatment Period		Baseline to Week 50
Secondary	Percentage Change from Baseline in Non-motor and Difficult to Count Seizures		Baseline to Week 50
Secondary	LGS: Percentage Change from Baseline in the Frequency of Observed Drop Seizures Over the Treatment Period		Baseline to Week 50