Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Sirolimus, Placebo.
- Who it may be relevant to
- Registry conditions: Tuberous Sclerosis Complex, Epilepsy. Basic parameters: 1 Day — 6 months · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
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.
Interventions
- Drug Sirolimus
The investigational drug product to be used in this study is sirolimus, provided in oral suspension. - Drug Placebo
Matching placebo
Primary outcome measures
- Efficacy -- time to seizure onset [Time frame: 12 months of age]
- Safety -- adverse events [Time frame: 12 months of age]
Secondary outcome measures (5)
- Neurodevelopmental Outcomes [Time frame: 12 and 24 months of age]
- Quality of Life Outcomes [Time frame: 12 and 24 months of age]
- EEG Biomarkers [Time frame: 12 and 24 months of age]
- MRI Biomarkers [Time frame: 12 and 24 months of age]
- Sirolimus Precision Dosing [Time frame: 12 months of age]
Eligibility criteria
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Triple blind
- Primary purpose
- Prevention
Study locations
United States · 11 centers
- University of Alabama at Birmingham — Birmingham
- University of California at Los Angeles — Los Angeles
- Stanford University — Palo Alto
- Children's Hospital Colorado — Aurora
- Lurie Children's Hospital of Chicago — Chicago
- Boston Children's Hospital — Boston
- Washington University -- St. Louis — St Louis
- University of North Carolina at Chapel Hill — Chapel Hill
- … and 3 more centers
Identifiers
NCT: NCT05104983 · 2021-0438 · 1R01FD007275