Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study (TSC-STEPS)

January 20, 2026 updated by: Darcy Krueger

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

64

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
          • Jessica Krefting, RN
        • Principal Investigator:
          • E. Martina Bebin, MD, MPA
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California at Los Angeles
        • Contact:
          • Angela Martinez
        • Principal Investigator:
          • Rajsekar Rajamaran, MD, MS
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University
        • Principal Investigator:
          • Brenda Porter, MD
        • Contact:
    • Colorado
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Boston Children's Hospital
        • Principal Investigator:
          • Mustafa Sahin, MD, PhD
        • Contact:
          • Sahana Raman
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University -- St. Louis
        • Contact:
          • Olga Novak
        • Principal Investigator:
          • Michael Wong, MD, PhD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27510
        • Active, not recruiting
        • University of North Carolina At Chapel Hill
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Darcy A Krueger, MD, PhD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas HSC at Houston
        • Principal Investigator:
          • Hope Northrup, MD
        • Contact:
          • Mariam Lugo Noguera
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Mikaela Morales
        • Principal Investigator:
          • Stephanie Randle, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 6 months (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Matching placebo
Experimental: Sirolimus
Drug: Sirolimus
The investigational drug product to be used in this study is sirolimus, provided in oral suspension.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy -- time to seizure onset
Time Frame: 12 months of age
Time to seizure onset, comparing sirolimus with placebo
12 months of age
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.
12 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neurodevelopmental Outcomes
Time Frame: 12 and 24 months of age
Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.
12 and 24 months of age
Quality of Life Outcomes
Time Frame: 12 and 24 months of age
Patient and caregiver quality of life, comparing sirolimus with placebo.
12 and 24 months of age
EEG Biomarkers
Time Frame: 12 and 24 months of age
EEG measures of neuronal connectivity, comparing sirolimus with placebo.
12 and 24 months of age
MRI Biomarkers
Time Frame: 12 and 24 months of age
MRI measures of neuronal connectivity, comparing sirolimus with placebo.
12 and 24 months of age
Sirolimus Precision Dosing
Time Frame: 12 months of age
Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC
12 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Darcy Krueger

Investigators

  • Principal Investigator: Darcy A Krueger, MD, PhD, Children's Hospital Medical Center, Cincinnati
  • Principal Investigator: Martina Bebin, MD, MPA, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 13, 2021

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

October 22, 2021

First Submitted That Met QC Criteria

October 22, 2021

First Posted (Actual)

November 3, 2021

Study Record Updates

Last Update Posted (Actual)

January 22, 2026

Last Update Submitted That Met QC Criteria

January 20, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-0438
  • 1R01FD007275 (U.S. FDA Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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