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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05104983
Recruitment Status : Recruiting
First Posted : November 3, 2021
Last Update Posted : June 9, 2022
Sponsor:
Information provided by (Responsible Party):
Darcy Krueger, Children's Hospital Medical Center, Cincinnati

Brief 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).


Condition or disease Intervention/treatment Phase
Tuberous Sclerosis Complex Epilepsy Drug: Sirolimus Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Actual Study Start Date : October 13, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : June 30, 2026


Arm Intervention/treatment
Experimental: Sirolimus
Sirolimus
Drug: Sirolimus
The investigational drug product to be used in this study is sirolimus, provided in oral suspension.

Placebo Comparator: Placebo
Placebo
Drug: Placebo
Matching placebo




Primary Outcome Measures :
  1. Efficacy -- time to seizure onset [ Time Frame: 12 months of age ]
    Time to seizure onset, comparing sirolimus with placebo

  2. 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.


Secondary Outcome Measures :
  1. Neurodevelopmental Outcomes [ Time Frame: 12 and 24 months of age ]
    Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.

  2. Quality of Life Outcomes [ Time Frame: 12 and 24 months of age ]
    Patient and caregiver quality of life, comparing sirolimus with placebo.

  3. EEG Biomarkers [ Time Frame: 12 and 24 months of age ]
    EEG measures of neuronal connectivity, comparing sirolimus with placebo.

  4. MRI Biomarkers [ Time Frame: 12 and 24 months of age ]
    MRI measures of neuronal connectivity, comparing sirolimus with placebo.

  5. Sirolimus Precision Dosing [ Time Frame: 12 months of age ]
    Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05104983


Contacts
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Contact: Molly S Griffith, BA 513-636-9669 info@tscsteps.org

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jessica Krefting, RN    526-533-0833    jessicakrefting@uabmc.edu   
Principal Investigator: E. Martina Bebin, MD, MPA         
United States, California
University of California at Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Angela Martinez    310-206-4037    angelamartinez@mednet.ucla.edu   
Principal Investigator: Rajsekar Rajamaran, MD, MS         
Stanford University Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Jennifer Winterbottom    650-498-9732    jwinter2@stanford.edu   
Principal Investigator: Brenda Porter, MD         
United States, Massachusetts
Boston Children's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Emine Arcasoy    617-919-7624    emine.arcasoy@childrens.harvard.edu   
Principal Investigator: Mustafa Sahin, MD, PhD         
United States, Missouri
Washington University -- St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Olga Novak    314-454-4267    novako@wustl.edu   
Principal Investigator: Michael Wong, MD, PhD         
United States, North Carolina
University of North Carolina at Chapel Hill Not yet recruiting
Chapel Hill, North Carolina, United States, 27510
Contact: Hannah Riehl    919-962-8462    hannah.riehl@cidd.unc.edu   
Principal Investigator: Jamie Capal, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Molly S Griffith, BA    513-636-9669    molly.griffith@cchmc.org   
Principal Investigator: Darcy A Krueger, MD, PhD         
United States, Texas
University of Texas HSC at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Saba Usmani    713-500-5766    saba.usmani@uth.tmc.edu   
Principal Investigator: Hope Northrup, MD         
Sponsors and Collaborators
Darcy Krueger
Investigators
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Principal Investigator: Darcy A Krueger, MD, PhD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Martina Bebin, MD, MPA University of Alabama at Birmingham
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Responsible Party: Darcy Krueger, IND Sponsor/Lead Principal Investigator, Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT05104983    
Other Study ID Numbers: 2021-0438
1R01FD007275 ( U.S. FDA Grant/Contract )
First Posted: November 3, 2021    Key Record Dates
Last Update Posted: June 9, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Darcy Krueger, Children's Hospital Medical Center, Cincinnati:
Tuberous Sclerosis Complex
TSC
epilepsy
prevention
mTOR
sirolimus
infant
Additional relevant MeSH terms:
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Tuberous Sclerosis
Epilepsy
Sclerosis
Pathologic Processes
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs