Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies (PACIFIC)

Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-escalation Study to Investigate the Safety, Tolerability, PK, PD, and Exploratory Efficacy of LP352 in Subjects With Developmental and Epileptic Encephalopathies

The objective of this study is to assess the safety, tolerability, efficacy, and pharmacokinetics of adjunctive therapy of LP352 in adults and adolescents with developmental and epileptic encephalopathies.

Study Overview

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

Detailed Description

This is a randomized, double-blind, parallel-group, dose-escalation, placebo-controlled study of LP352 in adults and adolescents with developmental and epileptic encephalopathies (DEE) with an average of ≥ 4 observed/countable motor seizures per 4-week period during the 12 weeks before screening while on stable antiseizure medicine (ASM).

Subjects will be randomized 4:1 to LP352 or placebo. The study will have a baseline period of 28 days, followed by a 15 day up-titration period during which time subjects will titrate up to their highest tolerated doses, and a 60-day maintenance period. After Day 75, subjects will be tapered down over a period of up to 15 days, with a follow-up visit 30 days after last dose. Enrolled subjects will be allowed to continue treatment with up to 4 concomitant ASMs at a stable dose.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane Women's Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Children's Hospital, Monash Health
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona - Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Downey, California, United States, 90242
      • Rancho Los Amigos National Rehabilitation Center (RLANRC)
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Northwest Florida Clinical Research Group
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
    • Orlando, Florida, United States, 32806
      • Research Institute of Orlando
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Pacific Neuroscience
  • Idaho
    • Boise, Idaho, United States, 83702
      • Consultants in Epilepsy and Neurology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Hawthorne, New York, United States, 10532
      • Boston Children's Health Physicians LLP
    • Mineola, New York, United States, 11501
      • New York University Langone Hospital - Long Island
    • New York, New York, United States, 10075
      • Northwell Health
    • Staten Island, New York, United States, 10305
      • Northeast Regional Epilepsy Group
  • North Carolina
    • Charlotte, North Carolina, United States, 98277
      • OnSite Clinical Solutions LLC
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Neurological Specialties-East
  • Texas
    • Austin, Texas, United States, 78758
      • Austin Epilepsy Care Center
    • Austin, Texas, United States, 78757
      • Child Neurology Consultants of Austin
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Renton, Washington, United States, 98055
      • 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

Key Inclusion Criteria:

1. Male or non-pregnant, non-lactating female, age 12 to 65 years
2. Diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or other developmental and epileptic encephalopathy
3. Has a minimum number of seizures per 4-week period while taking 1 to 4 anti-seizure medications
4. All medications and epilepsy interventions must be stable for 4 weeks before screening and are expected to remain stable during the study
5. The patient/parent/caregiver is able and willing to attend study visits, complete the diary and take study drug as instructed

Key Exclusion Criteria:

1. Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, pulmonary arterial hypertension or abnormal blood pressure
2. Has glaucoma, renal impairment, liver disease or any other medical condition that would affect study participation or pose a risk to the subject
3. Current or recent history of moderate or severe depression, anorexia nervosa, bulimia or at risk of suicidal behavior
4. Currently taking anorectic agents, monoamine oxidase inhibitors; serotonin agonists or antagonists including fenfluramine, atomoxetine, vortioxetine, or other medications for weight loss
5. 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

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 60-day maintenance period and a 15-day taper/down titration period.	Drug: LP352; LP352 administered three times daily, orally or through G-tube
Placebo Comparator: Placebo; Placebo for LP352	Drug: Placebo; Matching placebo for LP352 administered three times daily, orally or through G-tube; Other Names: Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent Adverse Events	Incidence and severity of 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 Day 75
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 Day 75
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 Day 75
Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Treatment Period		Baseline up to Day 75
Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance Period		Baseline up to Day 75

Secondary Outcome Measures

Outcome Measure	Time Frame
Observed Plasma Concentrations of LP352 by Time and Dose	Baseline up to Day 75
Modeled Estimate of Average Plasma Concentration	Baseline up to Day 75
Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing	Baseline up to Day 75
Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events	Baseline up to Day 75
Correlation of Plasma Concentration with Seizure Frequency	Baseline up to Day 75
Observed and Change from Baseline Prolactin Concentration During the Treatment Period	Baseline up to Day 75

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): March 3, 2022
• Primary Completion (Actual): November 16, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: March 22, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 6, 2022

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

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: LP352-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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