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

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

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.

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.

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.