Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 64
- Locations
- 11
- Primary Endpoint
- Efficacy -- time to seizure onset
Study Overview
Brief Summary
This trial is a Phase II randomized, double-blind, placebo controlled multi-site study to evaluate the safety and efficacy of early sirolimus to prevent or delay seizure onset in TSC infants.
This study is supported by research funding from the Office of Orphan Products Division (OOPD) of the US Food and Drug Administration (FDA).
Detailed Description
Tuberous Sclerosis Complex (TSC) is caused by genetic mutation in TSC1 or TSC2, resulting in dysregulation of the mechanistic target of rapamycin (mTOR) signaling pathway. Age at time of seizure onset in TSC infants has been linked to long-term neurodevelopmental outcome in this high-risk population. Sirolimus is an mTOR inhibitor used to treat many of the symptoms of TSC, including epilepsy. This will be the first study to truly evaluate a targeted, disease-modifying drug therapy for preventing or delaying seizure onset in TSC using a rational, mechanism-based therapeutic approach.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 1 Day to 6 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •0-6 months of age at the time of enrollment (subject must be <7 months of chronological age at time of randomization and treatment initiation). Corrected age must be at least 39 weeks (calculated by subtracting the number of weeks born before 40 weeks gestation from the chronological age).
- •Has a confirmed diagnosis of TSC based on established clinical or genetic criteria
Exclusion Criteria
- •Prior history of seizures (clinical or electrographic) at the time of enrollment or identified on baseline EEG.
- •Has been treated in the past or is currently being treated at the time of enrollment with conventional anticonvulsant medications (AEDs), systemic (oral) mTOR inhibitors (such as rapamycin, sirolimus, or everolimus), ketogenic-related special diet, or another anti-seizure therapeutic agent, device, or procedure.
- •Has taken any other investigational drug as part of another research study, within 30 days prior to the baseline screening visit.
- •Has a significant illness or active infection at the time of the baseline screening visit
- •Has a history of significant prematurity, defined as gestational age <30 weeks at the time of delivery, or other significant medical complications at birth or during the neonatal period that other than TSC would convey additional risk of seizures or neurodevelopmental delay (i.e. HIE, severe neonatal infection, major surgery, prolonged ventilatory or other life-saving supportive care or procedures).
- •Abnormal laboratory values at baseline (i.e., renal function, liver function, or bone marrow production) that are in the opinion of the investigator clinically significant and may jeopardize the safety of the study subject.
- •Prior, planned or anticipated neurosurgery within 3 months of the baseline visit
- •Has a TSC-associated condition for which mTOR treatment is clinically indicated (i.e. SEGA or AML).
- •Subjects who are, in the opinion of the investigator, unable to comply with the requirements of the study.
Arms & Interventions
Sirolimus
Sirolimus
Intervention: Sirolimus (Drug)
Placebo
Placebo
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Efficacy -- time to seizure onset
Time Frame: 12 months of age
Time to seizure onset, comparing sirolimus with placebo
Safety -- adverse events
Time Frame: 12 months of age
Percentage of subjects reporting severe (CTCAE v5.0 grade \>= 3) adverse event (AE) or serious adverse event (SAE), comparing sirolimus with placebo.
Secondary Outcomes
- MRI Biomarkers(12 and 24 months of age)
- Neurodevelopmental Outcomes(12 and 24 months of age)
- Sirolimus Precision Dosing(12 months of age)
- Quality of Life Outcomes(12 and 24 months of age)
- EEG Biomarkers(12 and 24 months of age)
Investigators
Darcy Krueger
IND Sponsor/Lead Principal Investigator
Children's Hospital Medical Center, Cincinnati