Clinical trial NCT05626634: Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: 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: 2022-11-25
Enrollment: 41
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-emergent Adverse Events
timeFrame: Baseline up to Week 52
measure: Columbia-Suicide Severity Rating Scale (C-SSRS) Response
timeFrame: Baseline up to Week 52
measure: Patient Health Questionnaire-9 Total Score and Question 9 Score
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Percent Change from Baseline in Observed Countable Motor Seizure Frequency During the Treatment Period
timeFrame: Baseline to Week 50
measure: Proportion of Subjects with > 50% Reduction in Total Seizures During the Treatment Period
timeFrame: Baseline to Week 50
measure: Percent Reduction in Individual Seizure Type During the Treatment Period
timeFrame: Baseline to Week 50
measure: Proportion of Subjects Requiring Rescue Medication During the Treatment Period
timeFrame: Baseline to Week 50
measure: Percent Change from Baseline in the Number of Episodes of Status Epilepticus During the Treatment Period
timeFrame: Baseline to Week 50
measure: Percent of Subjects with Countable Motor Seizure-free Days During the Treatment Period
timeFrame: Baseline to Week 50
measure: Percentage Change from Baseline in Non-motor and Difficult to Count Seizures
timeFrame: Baseline to Week 50
measure: LGS: Percentage Change from Baseline in the Frequency of Observed Drop Seizures Over the Treatment Period
timeFrame: Baseline to Week 50
Other outcomes:
Locations:
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: 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: 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: 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: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
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: