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

Sponsor

Longboard Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05626634

Collaborator

(none)

Enrollment

Locations

Arm

22.8

Anticipated Duration (Months)

2.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Developmental and Epileptic Encephalopathy Dravet Syndrome Lennox-Gastaut Syndrome	Drug: LP352	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 8, 2022

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LP352 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.	Drug: LP352 LP352 6 mg, 9 mg or 12 mg administered three times daily, orally or through G-tube

Arm

Intervention/Treatment

Experimental: LP352

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.

Drug: LP352

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

Outcome Measures

Primary Outcome Measures

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
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
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

Secondary Outcome Measures

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
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]
Percent of Subjects with Countable Motor Seizure-free Days During the Treatment Period [Baseline to Week 50]
Percentage Change from Baseline in Non-motor and Difficult to Count Seizures [Baseline to Week 50]
LGS: Percentage Change from Baseline in the Frequency of Observed Drop Seizures Over the Treatment Period [Baseline to Week 50]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	Rancho Los Amigos National Rehabilitation Center (RLANRC)	Downey	California	United States	90242
3	University of California San Francisco	San Francisco	California	United States	94158
4	Northwest Florida Clinical Research Group	Gulf Breeze	Florida	United States	32561
5	University of Miami	Miami	Florida	United States	33136
6	Advent Health Orlando	Orlando	Florida	United States	32803
7	Research Institute of Orlando	Orlando	Florida	United States	32806
8	University of South Florida	Tampa	Florida	United States	33606
9	Hawaii Pacific Neuroscience	Honolulu	Hawaii	United States	96817
10	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
11	Mid-Atlantic Epilepsy and Sleep Center	Bethesda	Maryland	United States	20817
12	Spectrum Health	Grand Rapids	Michigan	United States	49503
13	Mayo Clinic	Rochester	Minnesota	United States	55905
14	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
15	Boston Children's Health Physicians LLP	Hawthorne	New York	United States	10532
16	Northwell Health	New York	New York	United States	10075
17	Northeast Regional Epilepsy Group	Staten Island	New York	United States	10305
18	OnSite Clinical Solutions LLC	Charlotte	North Carolina	United States	98277
19	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27157
20	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
21	Providence Neurological Specialties-East	Portland	Oregon	United States	97213
22	Austin Epilepsy Care Center	Austin	Texas	United States	78758
23	University of Utah	Salt Lake City	Utah	United States	84132
24	University of Washington Valley Medical Center	Renton	Washington	United States	98055