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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
Contacten en locaties
Studiecontact
- Naam: Davis Ryman, MD, PhD
- Telefoonnummer: 510-961-1148
- E-mail: info@aeovian.com
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Kind
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: 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.
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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.
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Placebo-vergelijker: 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.
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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.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Change From Baseline in Seizure Frequency
Tijdsspanne: 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)
|
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Clinical Global Impression of Change (CGI-C)
Tijdsspanne: Week 12
|
Change from Baseline in symptoms of TSC, as evaluated by the study doctor.
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Week 12
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Medewerkers en onderzoekers
Sponsor
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Neurologische manifestaties
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Neoplasmata
- Genetische ziekten, aangeboren
- Neurodegeneratieve ziekten
- Aangeboren afwijkingen
- Heredodegeneratieve aandoeningen, zenuwstelsel
- Neoplastische syndromen, erfelijk
- Neurocutane syndromen
- Hamartoma
- Neoplasmata, meervoudig primair
- Misvormingen van corticale ontwikkeling, groep I
- Misvormingen van corticale ontwikkeling
- Misvormingen van het zenuwstelsel
- Aangeboren, erfelijke en neonatale ziekten en afwijkingen
- Pathologische aandoeningen, tekenen en symptomen
- Tekenen en symptomen
- Geneesmiddelenresistente epilepsie
- Tubereuze sclerose
- Epilepsie
- Aanvallen
Andere studie-ID-nummers
- CL-078-201
- 2025-522330-31 (EudraCT-nummer)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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