NCT05104983

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).

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
64

participants targeted

Target at P50-P75 for phase_2

Timeline
14mo left

Started Oct 2021

Longer than P75 for phase_2

Geographic Reach
1 country

11 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress80%
Oct 2021Jun 2027

Study Start

First participant enrolled

October 13, 2021

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

October 22, 2021

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 3, 2021

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2026

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Last Updated

January 22, 2026

Status Verified

January 1, 2026

Enrollment Period

4.7 years

First QC Date

October 22, 2021

Last Update Submit

January 20, 2026

Conditions

Keywords

Tuberous Sclerosis ComplexTSCepilepsypreventionmTORsirolimusinfant

Outcome Measures

Primary Outcomes (2)

  • Efficacy -- time to seizure onset

    Time to seizure onset, comparing sirolimus with placebo

    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.

    12 months of age

Secondary Outcomes (5)

  • Neurodevelopmental Outcomes

    12 and 24 months of age

  • Quality of Life Outcomes

    12 and 24 months of age

  • EEG Biomarkers

    12 and 24 months of age

  • MRI Biomarkers

    12 and 24 months of age

  • Sirolimus Precision Dosing

    12 months of age

Study Arms (2)

Sirolimus

EXPERIMENTAL

Sirolimus

Drug: Sirolimus

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

The investigational drug product to be used in this study is sirolimus, provided in oral suspension.

Sirolimus

Matching placebo

Placebo

Eligibility Criteria

Age1 Day - 6 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

University of California at Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Washington University -- St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27510, United States

ACTIVE NOT RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

University of Texas HSC at Houston

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

MeSH Terms

Conditions

Tuberous SclerosisEpilepsy

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

HamartomaNeoplasmsNeoplasms, Multiple PrimaryNeoplastic Syndromes, HereditaryMalformations of Cortical Development, Group IMalformations of Cortical DevelopmentNervous System MalformationsNervous System DiseasesNeurocutaneous SyndromesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, InbornBrain DiseasesCentral Nervous System Diseases

Intervention Hierarchy (Ancestors)

MacrolidesLactonesOrganic Chemicals

Study Officials

  • Darcy A Krueger, MD, PhD

    Children's Hospital Medical Center, Cincinnati

    PRINCIPAL INVESTIGATOR
  • Martina Bebin, MD, MPA

    University of Alabama at Birmingham

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Molly S Griffith, BA

CONTACT

Jessica Krefting, RN

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
IND Sponsor/Lead Principal Investigator

Study Record Dates

First Submitted

October 22, 2021

First Posted

November 3, 2021

Study Start

October 13, 2021

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 30, 2027

Last Updated

January 22, 2026

Record last verified: 2026-01

Locations