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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Dravet Syndrome; Lennox-Gastaut Syndrome; Developmental and Epileptic Encephalopathy
• Intervention / Treatment: Drug: LP352

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 Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Longboard Study Contact; Phone Number: 858-999-8858; Email: clinicalstudies@longboardpharma.com

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • Queensland Children's Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Health
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Hospital
  • California
    • Downey, California, United States, 90242
      • Recruiting
      • Rancho Los Amigos National Rehabilitation Center (RLANRC)
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Recruiting
      • Northwest Florida Clinical Research Group
    • Miami, Florida, United States, 33136
      • Not yet recruiting
      • University of Miami
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Research Institute of Orlando
    • Orlando, Florida, United States, 32803
      • Not yet recruiting
      • Advent Health Orlando
    • Tampa, Florida, United States, 33606
      • Recruiting
      • University of South Florida
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Recruiting
      • Hawaii Pacific Neuroscience
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Feinberg School of Medicine
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Spectrum Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • Hawthorne, New York, United States, 10532
      • Not yet recruiting
      • Boston Children's Health Physicians LLP
    • New York, New York, United States, 10075
      • Recruiting
      • Northwell Health
    • Staten Island, New York, United States, 10305
      • Not yet recruiting
      • Northeast Regional Epilepsy Group
  • North Carolina
    • Charlotte, North Carolina, United States, 98277
      • Not yet recruiting
      • OnSite Clinical Solutions LLC
    • Winston-Salem, North Carolina, United States, 27157
      • Not yet recruiting
      • Wake Forest University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Neurological Specialties-East
  • Texas
    • Austin, Texas, United States, 78758
      • Recruiting
      • Austin Epilepsy Care Center
    • Austin, Texas, United States, 78757
      • Recruiting
      • Child Neurology Consultants of Austin
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Recruiting
      • University of Utah
  • Washington
    • Renton, Washington, United States, 98055
      • Not yet recruiting
      • University of Washington Valley Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Longboard Pharmaceuticals
• Investigators: Principal Investigator: Dennis J Dlugos, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: November 15, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: epilepsy; Dravet Syndrome; CDKL5 deficiency disorder; developmental and epileptic encephalopathy; Lennox-Gastaut Syndrome; treatment resistant epilepsy; tuberous sclerosis complex
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Disease; Genetic Diseases, Inborn; Epilepsy; Epilepsies, Myoclonic; Syndrome; Brain Diseases; Lennox Gastaut Syndrome
• Other Study ID Numbers: LP352-202

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No