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 8 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
- 8 sitesUnited States
- Study dates
- 13 Oct 2021to 30 Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Boston Children's Hospital
Boston, Massachusetts, 02115
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27510
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Texas HSC at Houston
Houston, Texas, 77030
University of California at Los Angeles
Los Angeles, California, 90095
Stanford University
Palo Alto, California, 94304
Seattle Children's Hospital
Seattle, Washington, 98105
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
- Oct 2026
- First submitted
- 22 Oct 2021
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
- ClinicalTrials.gov ID
- NCT05104983
- Acronym / sponsor ID
- TSC-STEPS / 2021-0438
- Conditions
- Tuberous Sclerosis Complex, Epilepsy
- Keywords
- Tuberous Sclerosis Complex, TSC, epilepsy, prevention, mTOR, sirolimus, infant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Darcy KruegerUniversity, hospital or other
- Study start
- 13 Oct 2021 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 3 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusSirolimus |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 1 day to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusThe investigational drug product to be used in this study is sirolimus, provided in oral suspension. | Drug | Sirolimus |
| PlaceboMatching placebo | Drug | Placebo |
Primary outcome
Efficacy -- time to seizure onset
Time frame: 12 months of age
Time to seizure onset, comparing sirolimus with placebo
Safety -- adverse events
Time frame: 12 months of age
Percentage of subjects reporting severe (CTCAE v5.0 grade >= 3) adverse event (AE) or serious adverse event (SAE), comparing sirolimus with placebo.
5 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darcy A Krueger, MD, PhD principal investigator
Children's Hospital Medical Center, Cincinnati
Martina Bebin, MD, MPA principal investigator
University of Alabama at Birmingham
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus in people with Tuberous Sclerosis Complex and Epilepsy, run by Darcy Krueger at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy -- time to seizure onset (time frame: 12 months of age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.