A Phase 3, Placebo-Controlled Study to Investigate LP352 in Children and Adults With Dravet Syndrome (DS)

Official title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Investigate the Efficacy, Safety, and Tolerability of LP352 in the Treatment of Seizures in Children and Adults With Dravet Syndrome

Overview

This (DEEp SEA Study) is a double-blind, randomized, placebo-controlled, multicenter study to investigate the efficacy, safety, and tolerability of LP352 in the treatment of seizures in children and adults with DS. The study consists of 3 main phases: Screening, Titration period, and Maintenance period, followed by a Taper period and Follow-Up. Participants will be randomized to LP352 or placebo. The total duration of the study will be approximately 24 months.

Interventions

• Drug LP352
  LP352 will be administered orally or through G-tube/ percutaneous endoscopic gastrostomy (PEG) tube
• Drug Placebo
  Participants will be administered with matching placebo orally or through G-tube/ PEG tube

Primary outcome measures

• Frequency Percent Change in Countable Motor Seizures During Treatment Compared to Baseline [Time frame: Baseline and up to 15 Weeks]

Secondary outcome measures (3)

• Safety and Tolerability of LP352 [Time frame: Up to 21 Weeks]
• Percentage of participants with ≥ 50% Reduction in countable motor seizures during Treatment compared to Baseline [Time frame: Baseline and up to 15 Weeks]
• Frequency Percent Change in Countable Motor Seizures during Maintenance compared to Baseline [Time frame: Baseline and up to 15 Weeks]

Eligibility criteria

Inclusion criteria

• Diagnosis of DS must fulfill all of the following criteria:

• Participants with seizure onset age >1 and <20 months
• The participant has a history of at least 1 of the following seizure type(s): prolonged generalized tonic-clonic, hemiclonic, myoclonic, tonic, atonic, atypical absence, focal impaired awareness, nonconvulsive status epilepticus
• The participant has a current occurrence of at least 1 of the following countable motor seizure types: generalized tonic-clonic, tonic (bilateral), clonic (bilateral), atonic (bilateral) with truncal/leg involvement, focal motor (including hemiclonic), and focal to bilateral tonic-clonic
• The participant has demonstrated an average of at least 4 countable motor seizures per month for the 3 months prior to Screening.
• The participant has been taking 1 to 4 antiseizure medications (ASMs) at a stable dose for at least 4 weeks prior to Screening.
• The participant, parent, or caregiver is willing and able (in the judgment of the investigator) to comply with completion of the diaries throughout the study.
• The participant must be willing and able to provide written informed consent.

Exclusion criteria

• The participant has a history of infantile/epileptic spasms.
• The participant has been admitted to a medical facility for treatment of status epilepticus requiring mechanical ventilation within 3 months prior to Screening.
• The participant has a neurodegenerative disorder as indicated by magnetic resonance imaging or genetic testing.
• The participant has an acquired lesion/injury unrelated to the primary etiology that could contribute as a secondary cause of seizures.
• The participant is receiving exclusionary medications.
• The participant is currently using any cannabis product or cannabidiol that is not in oral solution/capsule/tablet form, not obtained from a government-approved dispensary, or contains ≥50% Delta-9-tetrahydrocannabinol (THC).
• The participant has unstable, clinically significant neurologic (other than the disease being studied, eg, recurrent strokes), psychiatric, cardiovascular (eg, pulmonary arterial hypertension, cardiac valvulopathy, orthostatic hypotension/tachycardia), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• The participant is unwilling to comply with any of the study requirements or timelines.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 25 centers

• Arkansas Children's Hospital - PIN — Little Rock
• Children's Hospital Los Angeles - PIN — Los Angeles
• David Geffen School of Medicine at UCLA — Los Angeles
• The Stanford Division of Child Neurology — Palo Alto
• UCSF Children's Hospital — San Francisco
• Children's Hospital Colorado. — Aurora
• Children's National Medical Center — Washington D.C.
• NW FL Clinical Research Group, LLC — Gulf Breeze
• … and 17 more centers

Japan · 10 centers

• IUHW Narita Hospital — Narita-shi
• Fukuoka Children's Hospital — Fukuoka
• Hokkaido University Hospital — Sapporo
• National Hospital Organization Nishi-Niigata Chuo National Hospital — Niigata
• Okayama University Hospital — Okayama
• Osaka City General Hospital — Osaka-Shi Miyakojima-Ku
• Saitama Prefectural Children's Medical Center — Saitama-shi
• National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders — Shizuoka
• … and 2 more centers

Australia · 8 centers

• Prince of Wales Hospital — Randwick
• Sydney Children's Hospital — Randwick
• Children's Hospital at Westmead — Westmead
• Royal Brisbane & Women's Hospital — Herston
• Queensland Children's Hospital — South Brisbane
• Austin Hospital — Heidelberg
• Royal Children's Hospital Melbourne — Parkville
• The Alfred Hospital — Melbourne

France · 8 centers

• Hôpital Roger Salengro — Lille
• Hospices Civils de Lyon - Hôpital Pierre Wertheimer — Bron
• AP-HM- Hôpital de La Timone — Marseille
• Hôpital Necker - Enfants Malades — Paris
• AP-HP - Hôpital universitaire Robert-Debré — Paris
• CHU de Rennes - Hôpital Pontchaillou — Rennes
• CHU de Strasbourg - Hôpital de Hautepierre — Strasbourg
• Centre Hospitalier Universitaire de Toulouse — Toulouse

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Brazil · 7 centers

• Instituto de Neurologia de Curitiba (INC) — Curitiba
• Hospital Moinhos de Vento — Porto Alegre
• Instituto do Cerebro do Rio Grande do Sul - InsCer — Porto Alegre
• Hospital das Clinicas - UNICAMP — Campinas
• Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP - PPDS — Ribeirão Preto
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS — São José do Rio Preto
• Instituto de Psiquiatria HC FMUSP — São Paulo

China · 6 centers

• Peking University First Hospital - Daxing Campus — Beijing
• The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Shenzhen Children's Hospital — Shenzhen
• Wuhan Children's Hospital — Wuhan
• Children's Hospital of Fudan University — Shanghai
• Beijing Children's Hospital, Capital Medical University - PIN — Beijing

Italy · 6 centers

• Fondazione Policlinico Universitario A Gemelli - Rome - PPDS — Rome
• Fondazione Istituto Neurologico Nazionale Casimiro Mondino IRCCS — Pavia
• Azienda Ospedaliero Universitaria A Meyer (Duplicate) — Florence
• Azienda Ospedaliera Universitaria Integrata Di Verona — Verona
• Istituto G Gaslini Ospedale Pediatrico IRCCS (Duplicate) — Genova
• IRCCS Ospedale Pediatrico Bambino Gesu — Roma

Germany · 5 centers

• Klinikum der Johann-Wolfgang Goethe-Universitat — Frankfurt am Main
• Universitätsklinikum Bonn — Bonn
• Gesellschaft für Epilepsieforschung e.V. — Bielefeld
• Universitätsklinikum Schleswig-Holstein - Campus Kiel — Kiel
• Epilepsie-Zentrum Bodensee — Ravensburg

Canada · 4 centers

• Children's and Women's Health Centre of British Columbia-4480 Oak St — Vancouver
• London Health Sciences Centre -800 Commissioners Rd E — London
• Hospital For Sick Children — Toronto
• Toronto Western Hospital — Toronto

Serbia · 4 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 4 centers

Center list to be confirmed — check the primary protocol.

Portugal · 3 centers

Center list to be confirmed — check the primary protocol.

Belgium · 2 centers

• UZ Leuven — Leuven
• UZ Antwerpen — Antwerp

Latvia · 1 center

Center list to be confirmed — check the primary protocol.

Mexico · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06660394 · LP352-302 · 2024-514937-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗