Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies

NCT05364021 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: LP352-201
• Study Type: interventional
• Target: 52
• Locations: 2 countries
• Sites: 34

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.

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• 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

Study Arms (2)

LP352

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Placebo for LP352

Drug: Placebo

Interventions

LP352 DRUG

LP352 administered three times daily, orally or through G-tube

LP352

Placebo DRUG

Matching placebo for LP352 administered three times daily, orally or through G-tube

Also known as: Placebo Comparator

Placebo

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, stroke, pulmonary arterial hypertension or abnormal blood pressure
• Has glaucoma, renal impairment, liver disease or any other medical condition that would affect study participation or pose a risk to the subject
• Current or recent history of moderate or severe depression, anorexia nervosa, bulimia or at risk of suicidal behavior
• Currently taking anorectic agents, monoamine oxidase inhibitors; serotonin agonists or antagonists including fenfluramine, atomoxetine, vortioxetine, or other medications for weight loss
• Positive test result on the drug screen, except tetrahydrocannabinol (THC) for patients taking prescribed cannabidiol

Sponsors & Collaborators

• Longboard Pharmaceuticals: lead

Study Sites (34)

University of Arizona - Health Sciences Center

Tucson, Arizona, 85724, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Rancho Los Amigos National Rehabilitation Center (RLANRC)

Downey, California, 90242, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California San Francisco

San Francisco, California, 94158, United States

Location

Northwest Florida Clinical Research Group

Gulf Breeze, Florida, 32561, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Advent Health Orlando

Orlando, Florida, 32803, United States

Location

Research Institute of Orlando

Orlando, Florida, 32806, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96817, United States

Location

Consultants in Epilepsy and Neurology

Boise, Idaho, 83702, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Boston Children's Health Physicians LLP

Hawthorne, New York, 10532, United States

Location

New York University Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

Northwell Health

New York, New York, 10075, United States

Location

Northeast Regional Epilepsy Group

Staten Island, New York, 10305, United States

Location

OnSite Clinical Solutions LLC

Charlotte, North Carolina, 98277, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Providence Neurological Specialties-East

Portland, Oregon, 97213, United States

Location

Child Neurology Consultants of Austin

Austin, Texas, 78757, United States

Location

Austin Epilepsy Care Center

Austin, Texas, 78758, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Washington Valley Medical Center

Renton, Washington, 98055, United States

Location

Royal Brisbane Women's Hospital

Herston, Queensland, 4029, Australia

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

Monash Children's Hospital, Monash Health

Clayton, Victoria, 3168, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Epilepsies, Myoclonic; Lennox Gastaut Syndrome; CDKL5 deficiency disorder; Epilepsy; Tuberous Sclerosis

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities

Study Officials

• Dennis J Dlugos, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: May 6, 2022
• Study Start: March 3, 2022
• Primary Completion: November 16, 2023
• Study Completion: November 20, 2023
• Last Updated: November 8, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); US (29)