Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study

Обзор

This trial is a Phase II randomized, double-blind, placebo controlled multi-site study to evaluate the safety and efficacy of early sirolimus to prevent or delay seizure onset in TSC infants. This study is supported by research funding from the Office of Orphan Products Division (OOPD) of the US Food and Drug Administration (FDA).

Подробное описание

Tuberous Sclerosis Complex (TSC) is caused by genetic mutation in TSC1 or TSC2, resulting in dysregulation of the mechanistic target of rapamycin (mTOR) signaling pathway. Age at time of seizure onset in TSC infants has been linked to long-term neurodevelopmental outcome in this high-risk population. Sirolimus is an mTOR inhibitor used to treat many of the symptoms of TSC, including epilepsy. This will be the first study to truly evaluate a targeted, disease-modifying drug therapy for preventing or delaying seizure onset in TSC using a rational, mechanism-based therapeutic approach.

Вмешательства

• Препарат Sirolimus
  The investigational drug product to be used in this study is sirolimus, provided in oral suspension.
• Препарат Placebo
  Matching placebo

Первичные конечные точки

• Efficacy -- time to seizure onset [Срок оценки: 12 months of age]
• Safety -- adverse events [Срок оценки: 12 months of age]

Вторичные конечные точки (5)

• Neurodevelopmental Outcomes [Срок оценки: 12 and 24 months of age]
• Quality of Life Outcomes [Срок оценки: 12 and 24 months of age]
• EEG Biomarkers [Срок оценки: 12 and 24 months of age]
• MRI Biomarkers [Срок оценки: 12 and 24 months of age]
• Sirolimus Precision Dosing [Срок оценки: 12 months of age]

Критерии участия

Критерии включения

• 0-6 months of age at the time of enrollment (subject must be <7 months of chronological age at time of randomization and treatment initiation). Corrected age must be at least 39 weeks (calculated by subtracting the number of weeks born before 40 weeks gestation from the chronological age).
• Has a confirmed diagnosis of TSC based on established clinical or genetic criteria

Критерии исключения

• Prior history of seizures (clinical or electrographic) at the time of enrollment or identified on baseline EEG.
• Has been treated in the past or is currently being treated at the time of enrollment with conventional anticonvulsant medications (AEDs), systemic (oral) mTOR inhibitors (such as rapamycin, sirolimus, or everolimus), ketogenic-related special diet, or another anti-seizure therapeutic agent, device, or procedure.
• Has taken any other investigational drug as part of another research study, within 30 days prior to the baseline screening visit.
• Has a significant illness or active infection at the time of the baseline screening visit
• Has a history of significant prematurity, defined as gestational age <30 weeks at the time of delivery, or other significant medical complications at birth or during the neonatal period that other than TSC would convey additional risk of seizures or neurodevelopmental delay (i.e. HIE, severe neonatal infection, major surgery, prolonged ventilatory or other life-saving supportive care or procedures).
• Abnormal laboratory values at baseline (i.e., renal function, liver function, or bone marrow production) that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
• Prior, planned or anticipated neurosurgery within 3 months of the baseline visit
• Has a TSC-associated condition for which mTOR treatment is clinically indicated (i.e. SEGA or AML).
• Subjects who are, in the opinion of the investigator, unable to comply with the requirements of the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

США · 11 центров

• University of Alabama at Birmingham — Birmingham
• University of California at Los Angeles — Los Angeles
• Stanford University — Palo Alto
• Children's Hospital Colorado — Aurora
• Lurie Children's Hospital of Chicago — Chicago
• Boston Children's Hospital — Boston
• Washington University -- St. Louis — St Louis
• University of North Carolina at Chapel Hill — Chapel Hill
• … и ещё 3 центра

Идентификаторы

NCT: NCT05104983 · 2021-0438 · 1R01FD007275

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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