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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 42
- 主要终点
- Change From Baseline in Seizure Frequency
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
This is a double-blind study in which participants, investigators, care providers, and outcome assessors are blinded to treatment assignment. Matching placebo is used to maintain blinding, and dose adjustments for placebo may be conducted in a manner similar to active treatment to preserve the blind.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
Participants will receive matching oral placebo once daily in addition to their stable background anti-seizure medication regimen for 12 weeks. Dose adjustments may be performed in a manner similar to active treatment to maintain blinding.
干预措施: Placebo (Drug)
AV078
Participants will receive oral AV078 once daily in addition to their stable background anti-seizure medication regimen for 12 weeks. Dosing will be titrated based on measured drug concentrations to achieve target exposure levels.
干预措施: AV078 (Drug)
结局指标
主要结局
Change From Baseline in Seizure Frequency
时间窗: Baseline (28-day period prior to treatment) to end of treatment (Week 12)
Change from Baseline in the number of seizures experienced in participants on active treatment. The number of seizures will be recorded by participants or their caregivers using a seizure diary.
Clinical Global Impression of Change (CGI-C)
时间窗: Week 12
Change from Baseline in symptoms of TSC, as evaluated by the study doctor.
次要结局
未报告次要终点