Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study

Epilepsy Clinical Trial

— TSC-STEPS  

Official title:

Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05104983
• Other study ID #: 2021-0438
• Secondary ID: 1R01FD007275
• Status: Recruiting
• Phase: Phase 2
• Start date: October 13, 2021
• Est. completion date: June 30, 2026

Study information

• Verified date: August 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Molly S Griffith, BA
• Phone: 513-636-9669
• Email: info[@]tscsteps.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: June 30, 2026
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 6 Months

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Sclerosis
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Intervention

Drug:
• Sirolimus
The investigational drug product to be used in this study is sirolimus, provided in oral suspension.
• Placebo
Matching placebo

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Texas HSC at Houston	Houston	Texas
United States	University of California at Los Angeles	Los Angeles	California
United States	Stanford University	Palo Alto	California
United States	Washington University -- St. Louis	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Darcy Krueger

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy -- time to seizure onset	Time to seizure onset, comparing sirolimus with placebo	12 months of age
Primary	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.	12 months of age
Secondary	Neurodevelopmental Outcomes	Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.	12 and 24 months of age
Secondary	Quality of Life Outcomes	Patient and caregiver quality of life, comparing sirolimus with placebo.	12 and 24 months of age
Secondary	EEG Biomarkers	EEG measures of neuronal connectivity, comparing sirolimus with placebo.	12 and 24 months of age
Secondary	MRI Biomarkers	MRI measures of neuronal connectivity, comparing sirolimus with placebo.	12 and 24 months of age
Secondary	Sirolimus Precision Dosing	Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC	12 months of age