Tuberous Sclerosis ComplexPhase 2TSC-STEPSNCT05104983
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
A Phase 2 study testing Sirolimus in people with Tuberous Sclerosis Complex and Epilepsy, run by Darcy Krueger at 11 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 1 day to 6 months
- Conditions the study is for
- Tuberous Sclerosis Complex, Epilepsy
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 11 sitesUnited States
- Study dates
- 13 Oct 2021to 30 Jun 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 10 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80045
Ryan Osselborn, 720-777-0493, ryan.osselborn@childrenscolorado.org
Marissa Anthony, 720-777-3119, marisa.anthony@childrenscolorado.org
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Jessica Krefting, RN
E. Martina Bebin, MD, MPA
- Recruiting
Boston Children's Hospital
Boston, Massachusetts, 02115
Sahana Raman
Mustafa Sahin, MD, PhD
- Active, not recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27510
- Recruiting
Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Enrique Rojas, 312-227-2532, erojas@luriechildrens.org
Sofia Mirshed, 312-227-4525, smirshed@luriechildrens.org
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Molly S Griffith, BA, 513-636-9669, info@tscsteps.org
Darcy A Krueger, MD, PhD
- Recruiting
University of Texas HSC at Houston
Houston, Texas, 77030
Mariam Lugo Noguera
Hope Northrup, MD
- Recruiting
University of California at Los Angeles
Los Angeles, California, 90095
Angela Martinez
Rajsekar Rajamaran, MD, MS
- Recruiting
Stanford University
Palo Alto, California, 94304
Rayann Solidum, rsolidum@stanford.edu
Brenda Porter, MD
- Recruiting
Seattle Children's Hospital
Seattle, Washington, 98105
Mikaela Morales
Stephanie Randle, MD
- Recruiting
Washington University -- St. Louis
St Louis, Missouri, 63110
Olga Novak
Michael Wong, MD, PhD
About this study
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).
Read the 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.
- Conditions
- Tuberous Sclerosis Complex, Epilepsy
- Being tested
- Sirolimus, Placebo
- Keywords
- Tuberous Sclerosis Complex, TSC, epilepsy, prevention, mTOR, sirolimus, infant
- Medical subject headings
- Tuberous Sclerosis, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
The investigational drug product to be used in this study is sirolimus, provided in oral suspension.
PlaceboDrug
Matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Sirolimus Receives: Drug: Sirolimus |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy -- time to seizure onset
Time to seizure onset, comparing sirolimus with placebo
Measured: 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.
Measured: 12 months of age
Secondary outcomes (5)
Neurodevelopmental Outcomes
Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.
Measured: 12 and 24 months of age
Quality of Life Outcomes
Patient and caregiver quality of life, comparing sirolimus with placebo.
Measured: 12 and 24 months of age
EEG Biomarkers
EEG measures of neuronal connectivity, comparing sirolimus with placebo.
Measured: 12 and 24 months of age
MRI Biomarkers
MRI measures of neuronal connectivity, comparing sirolimus with placebo.
Measured: 12 and 24 months of age
Sirolimus Precision Dosing
Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC
Measured: 12 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2021
- Study start13 Oct 2021
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tuberous Sclerosis ComplexStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Darcy Krueger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Darcy Krueger, Children's Hospital Medical Center, Cincinnati
- Investigators
- Darcy A Krueger, MD, PhD, Principal investigator, Children's Hospital Medical Center, CincinnatiMartina Bebin, MD, MPA, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05104983
- Sponsor's protocol ID
- 2021-0438
- Other IDs
- 1R01FD007275
- Acronym
- TSC-STEPS
- Status last verified
- Sep 2026
- First submitted
- 22 Oct 2021
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No