A Phase 2 Study of the Safety and Efficacy of AV078 in Participants With Tuberous Sclerosis Complex (TSC) Refractory Epilepsy (RESTOR-1)
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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Beräknad)
Fas
- Fas 2
Kontakter och platser
Studiekontakt
- Namn: Davis Ryman, MD, PhD
- Telefonnummer: 510-961-1148
- E-post: info@aeovian.com
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
- Barn
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Beskrivning
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.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
|
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.
|
|
Placebo-jämförare: 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.
|
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.
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Change From Baseline in Seizure Frequency
Tidsram: 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.
|
Baseline (28-day period prior to treatment) to end of treatment (Week 12)
|
|
Clinical Global Impression of Change (CGI-C)
Tidsram: Week 12
|
Change from Baseline in symptoms of TSC, as evaluated by the study doctor.
|
Week 12
|
Samarbetspartners och utredare
Sponsor
Studieavstämningsdatum
Studera stora datum
Studiestart (Beräknad)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Neurologiska manifestationer
- Hjärnsjukdomar
- Sjukdomar i centrala nervsystemet
- Sjukdomar i nervsystemet
- Neoplasmer
- Genetiska sjukdomar, medfödda
- Neurodegenerativa sjukdomar
- Medfödda abnormiteter
- Heredodegenerativa störningar, nervsystemet
- Neoplastiska syndrom, ärftligt
- Neurokutana syndrom
- Hamartoma
- Neoplasmer, multipla primära
- Missbildningar av kortikal utveckling, grupp I
- Missbildningar av kortikal utveckling
- Missbildningar i nervsystemet
- Medfödda, ärftliga och neonatala sjukdomar och abnormiteter
- Patologiska tillstånd, tecken och symtom
- Tecken och symtom
- Läkemedelsresistent epilepsi
- Tuberös skleros
- Epilepsi
- Anfall
Andra studie-ID-nummer
- CL-078-201
- 2025-522330-31 (EudraCT-nummer)
Plan för individuella deltagardata (IPD)
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Läkemedels- och apparatinformation, studiedokument
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