A Phase 2 Study of the Safety and Efficacy of AV078 in Participants With Tuberous Sclerosis Complex (TSC) Refractory Epilepsy

Официальное название

A Parallel-Group, Phase 2, Double-Blind, Placebo-Controlled, Randomized Study of the Safety and Efficacy of Oral AV078 in Participants With Tuberous Sclerosis Complex (TSC) Refractory Epilepsy

Обзор

This Phase 2, randomized, double-blind, placebo-controlled study will evaluate the safety, tolerability, and efficacy of oral AV078 in participants with refractory epilepsy due to tuberous sclerosis complex (TSC). Approximately 42 participants will be randomized in a 5:1 ratio to receive AV078 or placebo. The study will include a Screening Period collecting 4 weeks of pre-treatment Baseline data on seizure frequency, and progress to a 12-week Treatment Period, followed by an in person final follow-up visit approximately 2 weeks after the last dose.

Подробное описание

This study is a Phase 2, randomized, placebo controlled, double-blind, study that will evaluate the safety, tolerability, and efficacy of 12 weeks of treatment with AV078 (a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1) in participants with refractory epilepsy due to TSC.

Tuberous Sclerosis Complex (TSC) is a genetic disorder where mTOR1 complex 1 (or mTORC1) becomes more active than normal. This is an important cause of TSC symptoms, including epilepsy, which can be very difficult to treat.

Developing a drug to act directly on the mTORC1 complex, reducing its activity, may be an effective way to treat the unmet medical needs of patients with TSC epilepsy, potentially with fewer side effects than existing medications.

The purpose of this study is to determine, over a 12-week treatment period, if the investigational drug AV078 is safe and can reduce seizures in people with TSC. AV078, the "study drug," is a unique medication that can decrease the activity of mTORC1.

Approximately 42 participants will be enrolled and randomized in a 5:1 ratio to receive oral AV078 or matching placebo in addition to their existing stable anti-seizure medication regimen. Five participants aged 18 years and above will enrolled and dosed for at least four weeks before participants aged 12 years and above can be eligible to enroll.

The study consists of:

* A screening period of approximately 4 to 6 weeks * A 12-week treatment period during which participants receive once-daily dosing of AV078 or placebo * A follow-up visit approximately 2 weeks after the end of treatment

Dose adjustments of AV078 may be performed based on measured drug concentrations to achieve target exposure levels. Safety assessments will include monitoring of adverse events, laboratory tests, vital signs, electrocardiograms, and other clinical evaluations. Efficacy will be assessed primarily through changes in seizure frequency.

Вмешательства

• Препарат AV078
  AV078 is a selective inhibitor of mammalian target of rapamycin complex 1 (mTORC1) administered orally once daily. Dosing may be adjusted based on measured drug concentrations to achieve target exposure levels.
• Препарат Placebo
  Matching oral placebo administered once daily. The placebo is formulated to match AV078 and may undergo dose adjustments similar to active treatment to maintain blinding.

Первичные конечные точки

• Change From Baseline in Seizure Frequency [Срок оценки: Baseline (28-day period prior to treatment) to end of treatment (Week 12)]
• Clinical Global Impression of Change (CGI-C) [Срок оценки: Week 12]

Критерии участия

Критерии включения

• Participants aged 12 years and above.
• Diagnosis of TSC based on International TSC Consensus Group criteria.
• History of failure to adequately control seizures despite having been treated by two or more regimens of anti-seizure medications (ASMs).
• Receiving a stable dose of ASMs for at least 4 weeks at the start of the Screening Period and for the duration of the study.

Критерии исключения

• History of any infection requiring use of antibiotics within the last four weeks.
• Current or history of any clinically significant mental or physical illness or condition other than TSC that the Investigator believes would create significant risk for participation in the study.
• Recent epilepsy surgery/major surgery or planned surgery during the study.
• Treatment with medicines which act in a similar way.
• Treatment with medicines that suppress the immune system.
• Treatment with medicines that may significantly affect the way the body handles the study drug.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07680322 · CL-078-201 · 2025-522330-31

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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