Clinical trial NCT05364021: Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Developmental and Epileptic Encephalopathy
Dravet Syndrome
Lennox Gastaut Syndrome
Keywords: CDKL5 deficiency disorder
developmental and epileptic encephalopathy
Dravet Syndrome
epilepsy
Lennox-Gastaut Syndrome
treatment resistant epilepsy
tuberous sclerosis complex
Lead sponsor: Longboard Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-05-06
Enrollment: 52
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-emergent Adverse Events
timeFrame: Baseline up to Day 75
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) Response
timeFrame: Baseline up to Day 75
measure: Patient Health Questionnaire-9 Total Score and Question 9 Score
timeFrame: Baseline up to Day 75
measure: Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Treatment Period
timeFrame: Baseline up to Day 75
measure: Percent Change from Baseline in Observed Countable Motor Seizure Frequency (per 28 Days) During the Maintenance Period
timeFrame: Baseline up to Day 75
Secondary outcomes:
measure: Observed Plasma Concentrations of LP352 by Time and Dose
timeFrame: Baseline up to Day 75
measure: Modeled Estimate of Average Plasma Concentration
timeFrame: Baseline up to Day 75
measure: Modeled Estimate of Observed Plasma Concentration Just Prior to Dosing
timeFrame: Baseline up to Day 75
measure: Correlation of Plasma Concentration with Incidence of Treatment-emergent Adverse Events
timeFrame: Baseline up to Day 75
measure: Correlation of Plasma Concentration with Seizure Frequency
timeFrame: Baseline up to Day 75
measure: Observed and Change from Baseline Prolactin Concentration During the Treatment Period
timeFrame: Baseline up to Day 75
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona - Health Sciences Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Downey
country: United States
facility: Rancho Los Amigos National Rehabilitation Center (RLANRC)
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Gulf Breeze
country: United States
facility: Northwest Florida Clinical Research Group
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Orlando
country: United States
facility: Research Institute of Orlando
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience
state: Hawaii
city: Boise
country: United States
facility: Consultants in Epilepsy and Neurology
state: Idaho
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Bethesda
country: United States
facility: Mid-Atlantic Epilepsy and Sleep Center
state: Maryland
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hawthorne
country: United States
facility: Boston Children's Health Physicians LLP
state: New York
city: Mineola
country: United States
facility: New York University Langone Hospital - Long Island
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Staten Island
country: United States
facility: Northeast Regional Epilepsy Group
state: New York
city: Charlotte
country: United States
facility: OnSite Clinical Solutions LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Neurological Specialties-East
state: Oregon
city: Austin
country: United States
facility: Child Neurology Consultants of Austin
state: Texas
city: Austin
country: United States
facility: Austin Epilepsy Care Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Renton
country: United States
facility: University of Washington Valley Medical Center
state: Washington
city: Herston
country: Australia
facility: Royal Brisbane Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Children's Hospital, Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Dennis J Dlugos, MD
role: PRINCIPAL_INVESTIGATOR
References: