Clinical trial NCT04595513: Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants
Official title: Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tuberous Sclerosis Complex
Epilepsy
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2020-10-20
Enrollment: 5
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This trial is a single stage, phase I/II clinical trial design. Treatment is open-label to verify safety and dosing for TAVT-18 in TSC infants.

Note that this clinical trial originally planned for a follow-up second stage employing a randomized, double-blind, placebo-controlled multisite design. In October 2021, the second stage of this study was replaced by the TSC-STEPS clinical trial (clinicaltrials.gov NCT05104983).
Primary purpose: PREVENTION

Brief summary: This phase I/II clinical trial is an open-label clinical trial design to verify safety and dosing for TAVT-18 (sirolimus) powder for oral solution in TSC infants (N=5).

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. TAVT-18 is a novel formulation of sirolimus, an mTOR inhibitor. This study evaluates TAVT-18 as 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:

* 0-6 months of age at the time of enrollment (randomization and treatment initiation must occur before 7 months of age and infants born prematurely must have a corrected age of at least 39 weeks, calculated by subtracting the number of weeks born before 40 weeks gestation from the actual chronological age, in weeks)
* 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

Primary outcomes:
measure: Safety - Adverse Events
timeFrame: 12 months of age
measure: Efficacy - Time to Seizure Onset
timeFrame: 12 months of age
Secondary outcomes:
measure: Treatment Discontinuance Due to Adverse Events
timeFrame: 12 months of age
measure: Treatment Disruption Due to Adverse Events
timeFrame: 12 months of age
measure: Precision Dosing Accuracy
timeFrame: 12 months of age
measure: Age at Seizure Onset
timeFrame: 12 and 24 months of age
measure: Seizure Type
timeFrame: 12 and 24 months of age
measure: Seizure Frequency
timeFrame: 12 and 24 months of age
measure: TAND Severity Assessed by the TAND-L Checklist
timeFrame: 12 and 24 months of age
measure: Adaptive Behavior Assessed by the the VABS
timeFrame: 12 and 24 months of age
measure: Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
timeFrame: 12 and 24 months of age
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Darcy Krueger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: