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).
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
64
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGUniversity of California at Los Angeles
Los Angeles, California, United States
RECRUITINGEfficacy -- time to seizure onset
Time to seizure onset, comparing sirolimus with placebo
Time frame: 12 months of age
Safety -- adverse events
Percentage of subjects reporting severe (CTCAE v5.0 grade \>= 3) adverse event (AE) or serious adverse event (SAE), comparing sirolimus with placebo.
Time frame: 12 months of age
Neurodevelopmental Outcomes
Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.
Time frame: 12 and 24 months of age
Quality of Life Outcomes
Patient and caregiver quality of life, comparing sirolimus with placebo.
Time frame: 12 and 24 months of age
EEG Biomarkers
EEG measures of neuronal connectivity, comparing sirolimus with placebo.
Time frame: 12 and 24 months of age
MRI Biomarkers
MRI measures of neuronal connectivity, comparing sirolimus with placebo.
Time frame: 12 and 24 months of age
Sirolimus Precision Dosing
Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC
Time frame: 12 months of age
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Stanford University
Palo Alto, California, United States
RECRUITINGChildren's Hospital Colorado
Aurora, Colorado, United States
RECRUITINGLurie Children's Hospital of Chicago
Chicago, Illinois, United States
RECRUITINGBoston Children's Hospital
Boston, Massachusetts, United States
RECRUITINGWashington University -- St. Louis
St Louis, Missouri, United States
RECRUITINGUniversity of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
ACTIVE_NOT_RECRUITINGCincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
RECRUITINGUniversity of Texas HSC at Houston
Houston, Texas, United States
RECRUITING...and 1 more locations