Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies

Dravet Syndrome Clinical Trial

— PACIFIC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05364021
• Other study ID #: LP352-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 3, 2022
• Est. completion date: November 20, 2023

Study information

• Verified date: January 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 safety, tolerability, efficacy, and pharmacokinetics of adjunctive therapy of LP352 in adults and adolescents with developmental and epileptic encephalopathies.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 20, 2023
• Est. primary completion date: November 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• LP352
LP352 administered three times daily, orally or through G-tube
• Placebo
Matching placebo for LP352 administered three times daily, orally or through G-tube

Locations

Country	Name	City	State
Australia	Monash Children's Hospital, Monash Health	Clayton	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane Women's Hospital	Herston	Queensland
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	Consultants in Epilepsy and Neurology	Boise	Idaho
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	New York University Langone Hospital - Long Island	Mineola	New York
United States	Northwell Health	New York	New York
United States	Children's Hospital of Orange County	Orange	California
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	University of Arizona - Health Sciences Center	Tucson	Arizona
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 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
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 Day 75
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 Day 75
Primary	Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Treatment Period		Baseline up to Day 75
Primary	Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance Period		Baseline up to Day 75
Secondary	Observed Plasma Concentrations of LP352 by Time and Dose		Baseline up to Day 75
Secondary	Modeled Estimate of Average Plasma Concentration		Baseline up to Day 75
Secondary	Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing		Baseline up to Day 75
Secondary	Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events		Baseline up to Day 75
Secondary	Correlation of Plasma Concentration with Seizure Frequency		Baseline up to Day 75
Secondary	Observed and Change from Baseline Prolactin Concentration During the Treatment Period		Baseline up to Day 75