Back to resultsStopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study (TSC-STEPS)
Primary Purpose
Tuberous Sclerosis Complex, Epilepsy
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sirolimus
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Tuberous Sclerosis Complex focused on measuring Tuberous Sclerosis Complex, TSC, epilepsy, prevention, mTOR, sirolimus, infant
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- University of Alabama at BirminghamRecruiting
- University of California at Los AngelesRecruiting
- Stanford UniversityRecruiting
- Boston Children's HospitalRecruiting
- Washington University -- St. LouisRecruiting
- University of North Carolina at Chapel HillRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- University of Texas HSC at HoustonRecruiting
- Seattle Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sirolimus
Placebo
Arm Description
Sirolimus
Placebo
Outcomes
Primary Outcome Measures
Efficacy -- time to seizure onset
Time to seizure onset, comparing sirolimus with placebo
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.
Secondary Outcome Measures
Neurodevelopmental Outcomes
Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.
Quality of Life Outcomes
Patient and caregiver quality of life, comparing sirolimus with placebo.
EEG Biomarkers
EEG measures of neuronal connectivity, comparing sirolimus with placebo.
MRI Biomarkers
MRI measures of neuronal connectivity, comparing sirolimus with placebo.
Sirolimus Precision Dosing
Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05104983
Brief Title
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Acronym
TSC-STEPS
Official Title
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 13, 2021 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Darcy Krueger
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberous Sclerosis Complex, Epilepsy
Keywords
Tuberous Sclerosis Complex, TSC, epilepsy, prevention, mTOR, sirolimus, infant
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
64 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sirolimus
Arm Type
Experimental
Arm Description
Sirolimus
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Intervention Description
The investigational drug product to be used in this study is sirolimus, provided in oral suspension.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
Efficacy -- time to seizure onset
Description
Time to seizure onset, comparing sirolimus with placebo
Time Frame
12 months of age
Title
Safety -- adverse events
Description
Percentage of subjects reporting severe (CTCAE v5.0 grade >= 3) adverse event (AE) or serious adverse event (SAE), comparing sirolimus with placebo.
Time Frame
12 months of age
Secondary Outcome Measure Information:
Title
Neurodevelopmental Outcomes
Description
Neurodevelopmental outcomes at the end of treatment, comparing sirolimus with placebo.
Time Frame
12 and 24 months of age
Title
Quality of Life Outcomes
Description
Patient and caregiver quality of life, comparing sirolimus with placebo.
Time Frame
12 and 24 months of age
Title
EEG Biomarkers
Description
EEG measures of neuronal connectivity, comparing sirolimus with placebo.
Time Frame
12 and 24 months of age
Title
MRI Biomarkers
Description
MRI measures of neuronal connectivity, comparing sirolimus with placebo.
Time Frame
12 and 24 months of age
Title
Sirolimus Precision Dosing
Description
Validate the feasibility and effectiveness of sirolimus precision dosing in infants with TSC
Time Frame
12 months of age
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Molly S Griffith, BA
Phone
513-636-9669
Email
info@tscsteps.org
First Name & Middle Initial & Last Name or Official Title & Degree
Jessica Krefting, RN
Phone
256-533-0833
Email
info@tscsteps.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Darcy A Krueger, MD, PhD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Martina Bebin, MD, MPA
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Krefting, RN
First Name & Middle Initial & Last Name & Degree
E. Martina Bebin, MD, MPA
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angela Martinez
First Name & Middle Initial & Last Name & Degree
Rajsekar Rajamaran, MD, MS
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Winterbottom
First Name & Middle Initial & Last Name & Degree
Brenda Porter, MD
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emine Arcasoy
First Name & Middle Initial & Last Name & Degree
Mustafa Sahin, MD, PhD
Facility Name
Washington University -- St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olga Novak
First Name & Middle Initial & Last Name & Degree
Michael Wong, MD, PhD
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27510
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hannah Riehl
First Name & Middle Initial & Last Name & Degree
Jamie Capal, MD
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Molly S Griffith, BA
Phone
513-636-9669
Email
info@tscsteps.org
First Name & Middle Initial & Last Name & Degree
Darcy A Krueger, MD, PhD
Facility Name
University of Texas HSC at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alexis Rodriguez
First Name & Middle Initial & Last Name & Degree
Hope Northrup, MD
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mikaela Morales
First Name & Middle Initial & Last Name & Degree
Stephanie Randle, MD
12. IPD Sharing Statement
Learn more about this trial
Stopping TSC Onset and Progression 2B: Sirolimus TSC Epilepsy Prevention Study
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