Clinical trial NCT05104983: Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Official title: Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Tuberous Sclerosis Complex
Epilepsy
Keywords: Tuberous Sclerosis Complex
TSC
epilepsy
prevention
mTOR
sirolimus
infant
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2021-11-03
Enrollment: 64
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial will employ a randomized, double-blind, placebo-controlled multisite design to evaluate the safety and efficacy of early sirolimus treatment to prevent or delay seizure onset in TSC infants.
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Has a confirmed diagnosis of TSC based on established clinical or genetic criteria

Exclusion Criteria:

1. Prior history of seizures (clinical or electrographic) at the time of enrollment or identified on baseline EEG.
2. 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.
3. Has taken any other investigational drug as part of another research study, within 30 days prior to the baseline screening visit.
4. Has a significant illness or active infection at the time of the baseline screening visit
5. 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).
6. 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.
7. Prior, planned or anticipated neurosurgery within 3 months of the baseline visit
8. Has a TSC-associated condition for which mTOR treatment is clinically indicated (i.e. SEGA or AML).
9. Subjects who are, in the opinion of the investigator, unable to comply with the requirements of the study.

Primary outcomes:
measure: Efficacy -- time to seizure onset
timeFrame: 12 months of age
measure: Safety -- adverse events
timeFrame: 12 months of age
Secondary outcomes:
measure: Neurodevelopmental Outcomes
timeFrame: 12 and 24 months of age
measure: Quality of Life Outcomes
timeFrame: 12 and 24 months of age
measure: EEG Biomarkers
timeFrame: 12 and 24 months of age
measure: MRI Biomarkers
timeFrame: 12 and 24 months of age
measure: Sirolimus Precision Dosing
timeFrame: 12 months of age
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California at Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University -- St. Louis
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: University of Texas HSC at Houston
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Darcy A Krueger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama at Birmingham
name: Martina Bebin, MD, MPA
role: PRINCIPAL_INVESTIGATOR
References: