A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)

Официальное название

A Phase 3, Open-Label Study to Investigate the Long-Term Safety and Efficacy of LP352 in the Treatment of Seizures in Children and Adults With Developmental and Epileptic Encephalopathy

Обзор

This (DEEp OLE Study) is a multicentre, open-label study to investigate the long-term safety, efficacy, tolerability, and pharmacokinetics (PK) of LP352 in the treatment of seizures in children and adults with DEE who completed Study LP352-301 or LP352-302. The study consists of 3 main phases: Screening, Titration period and Maintenance period, followed by a Taper period and Follow-Up. The total duration of the study will be approximately 14 months.

Вмешательства

• Препарат LP352
  LP352 will be administered orally or through G-tube/ percutaneous endoscopic gastrostomy (PEG) tube.

Первичные конечные точки

• Number of participants reporting Treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) and AEs leading to discontinuation [Срок оценки: Up to 61 Weeks]
• Number of Participants With Clinically Significant Changes in Chemistry parameters [Срок оценки: Up to 61 Weeks]
• Number of Participants With Clinically Significant Changes in Hematology parameters [Срок оценки: Up to 61 Weeks]
• Number of Participants With Clinically Significant Changes in Urinalysis [Срок оценки: Up to 61 Weeks]
• Number of participants with clinically significant changes in vital signs [Срок оценки: Up to 61 Weeks]
• Number of participants with clinically significant changes in physical examinations [Срок оценки: Up to 61 Weeks]
• Number of participants with clinically significant changes in growth parameters [Срок оценки: Up to 61 Weeks]
• Number of participants with clinically significant changes in electrocardiogram (ECG) parameters [Срок оценки: Up to 61 Weeks]
• Number of participants with postive responses to Columbia-Suicide Severity Rating Scale (C-SSRS) [Срок оценки: Up to 61 Weeks]
• Number of participants with positive responses to Patient Health Questionnaire-9 (PHQ-9) and Question 9 [Срок оценки: Up to 61 Weeks]

Вторичные конечные точки (3)

• Frequency Percent Change in Countable Motor Seizures During Treatment Compared to Baseline [Срок оценки: Baseline and up to 55 weeks]
• Percentage of participants with ≥ 50% Reduction in countable motor seizures during Treatment compared to Baseline [Visit 1 of LP352-301 and LP352-302] [Срок оценки: Baseline and up to 55 weeks]
• Frequency Percent Change in Countable Motor Seizures during Maintenance compared to Baseline [Visit 1 of LP352-301 and LP352-302] [Срок оценки: Baseline and up to 55 weeks]

Критерии участия

Критерии включения

• The participant has satisfactorily completed Study LP352-301 or LP352-302 Visit 8, and who, in the opinion of the investigator, may benefit from continued LP352 administration.
• Diagnosis of DEE that includes Dravet Syndrome (DS), Lennox-Gastaut Syndrome (LGS), or DEE Other (as defined and evaluated in Study LP352-301 or LP352-302).
• Participant has a body weight of ≥10 kg.
• G-tubes/PEG tubes (if applicable) should be in stable and good working condition. Nasogastric tubes are not allowed except for short-term management.
• Has at least one reliable and consistent parent, legal guardian, or caregiver during the study.
• The participant must be willing and able to provide written informed consent; in instances where the participant is unable to provide consent, an appropriate LAR must provide informed consent and the participant will need to assent (as per local regulations) before participation in the study. If the participant cannot provide consent or assent (ie, due to developmental status), the investigator should document why it was not obtained.
• The participant and/or authorized representative is willing to provide written consent or assent to allow the investigator and the investigator's staff to consult with the participant's medical caregivers and the medical monitor during Screening and during participation in the study.
• All participants of childbearing potential must have a negative urine or serum pregnancy (human chorionic gonadotropin) test at Visit 8 from Study LP352-301 or LP352-302 and agrees to routinely use an acceptable effective method of contraception from the time of signing informed consent up to 48 hours after the last dose of study drug.
• Participant and/or participant's caregiver(s) agree to not post any participant's personal medical data related to the study or information related to the study on any website or social media site until the study has been completed.
• 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.

Критерии исключения

• The participant is receiving exclusionary medications.
• Considered at risk of suicidal behavior based on the C-SSRS at Visit 8 of LP352-301 or LP352-302. If the participant is unable to complete the C-SSRS due to developmental status, the participant's LAR may not complete the C-SSRS. In these cases, the investigator may use clinical judgment to assess both the participant's status regarding suicidality and the ability to complete the scale, both of which must then be documented in the source document.
• Has a PHQ-9 score of >9 or a positive response to Question 9 at Visit 8 of LP352-301 or LP352-302. If the participant is unable to complete the PHQ-9, the participant's LAR may not complete the PHQ-9. In these cases, the investigator may use clinical judgment to assess both the participant's status and ability to complete the scale, both of which must then be documented in the source document.
• Ongoing AE from LP352-301 or LP352-302 of severe depression, anorexia nervosa, or bulimia per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
• Has an abnormal and clinically significant 12-lead ECG at Visit 8 in LP352-301 or LP352-302 in the opinion of the investigator, for example, second- or third-degree heart block or a QTc of >450 msec for adult males, >470 msec for adult females, or >440 msec for pediatric participants.
• Ongoing AE in LP352-301 or LP352-302 of alcohol, opioid, or other drug use disorder, as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
• Current use of any cannabis product or cannabidiol that is not in oral solution/capsule/tablet form, not obtained from a government-approved dispensary, or containing ≥50% THC. Cannabis product or cannabidiol should be used primarily to treat seizures and dose should not be adjusted for the duration of the study. Cannabis product or cannabidiol will count as a concurrent ASM.
• Has a positive result on the urine drug screen at Visit 8 of LP352-301 or LP352-302, except for positive results related to prescribed controlled medications (eg, benzodiazepine) or Epidiolex®/government-approved cannabis product/cannabidiol used to treat seizures (eg, tetrahydrocannabinol).
• 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 (severe hepatic impairment), renal (severe renal impairment), metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality at Visit 8 of LP352-301 or LP352-302 which may impact the ability of the participant to participate or potentially confound the study results.
• Is pregnant, breast-feeding, or intending to become pregnant during or within 48 hours after the last dose of study drug; or intending to donate ova during such time period.
• Has a known hypersensitivity to any component of LP352 formulation or any history of serious drug-induced hypersensitivity, eg, toxic epidermal necrolysis or Drug Reaction with Eosinophilia and Systemic Symptoms.
• Unwilling to abstain from donation of blood during and within 2 weeks after the study.
• Is unable or unwilling to comply with any of the study requirements or timelines.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 19 центров

• Arkansas Children's Hospital - PIN — Little Rock
• David Geffen School of Medicine at UCLA — Los Angeles
• The Stanford Division of Child Neurology — Palo Alto
• UCSF Children's Hospital — San Francisco
• Childrens Hospital Colorado - PIN — Aurora
• NW FL Clinical Research Group, LLC — Gulf Breeze
• University of Miami - 1120 NW 14th St — Miami
• Research Institute of Orlando LLC — Orlando
• … и ещё 11 центров

Испания · 9 центров

• Hospital Sant Joan de Deu - PIN — Espluges de Llobregat
• Hospital Regional Universitario de Malaga - Hospital General — Málaga
• Hospital Universitario de Navarra — Pamplona
• Hospital Universitario Vall d'Hebron - PPDS — Barcelona
• Hospital de La Santa Creu i Sant Pau — Barcelona
• Hospital Infantil Universitario Niño Jesus - PIN — Madrid
• Hospital Universitario Vithas Madrid La Milagrosa — Madrid
• Hospital Ruber Internacional (Grupo Quironsalud) — Madrid
• … и ещё 1 центр

Италия · 6 центров

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

Австралия · 5 центров

• 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

Китай · 5 центров

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

Франция · 5 центров

• CHU de Strasbourg - Hôpital de Hautepierre — Strasbourg
• Hôpital Roger Salengro — Lille
• Hospices Civils de Lyon - Hôpital Pierre Wertheimer — Bron
• AP-HM- Hôpital de La Timone — Marseille
• AP-HP - Hôpital universitaire Robert-Debré — Paris

Япония · 4 центра

• IUHW Narita Hospital — Narita
• Saitama Prefectural Children's Medical Center — Saitama-shi
• National Hospital Organization Shizuoka Institute of Epilepsy and Neurological Disorders — Shizuoka
• National Center of Neurology and Psychiatry — Kodaira-Shi

Португалия · 3 центра

• ULS de Santa Maria,EPE - Hospital de Santa Maria - PPDS — Lisbon
• ULS de Coimbra, EPE - Hospital Pediátrico de Coimbra — Coimbra
• ULS de Santo António, EPE - Centro Materno Infantil Norte — Porto

Сербия · 3 центра

• University Clinical Center of Serbia - Dr Subotica 6 - PPDS — Belgrade
• Clinic for Neurology and Psychiatry for Children and Youth — Belgrade
• Mother and Child Health Care Institute of Serbia Dr Vukan Cupic — Belgrade

Великобритания · 3 центра

• Queen Elizabeth University Hospital - PPDS — Glasgow
• Great Ormond Street Hospital - PPDS — London
• University College London Hospitals (UCLH) - PPDS — London

Бразилия · 2 центра

• Instituto de Neurologia de Curitiba (INC) — Curitiba
• Instituto de Psiquiatria HC FMUSP — São Paulo

Германия · 2 центра

• Universitätsklinikum Bonn — Bonn
• Gesellschaft für Epilepsieforschung e.V. — Bielefeld

Бельгия · 1 центр

• UZ Antwerpen — Edegem

Латвия · 1 центр

• Children's Clinical University Hospital — Riga

Идентификаторы

NCT: NCT06908226 · LP352-303 · 2024-514974-39-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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