- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04595513
Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants (STOP2)
March 21, 2023 updated by: Children's Hospital Medical Center, Cincinnati
This phase I/II clinical trial is an open-label clinical trial design to verify safety and dosing for TAVT-18 (sirolimus) powder for oral solution in TSC infants (N=5).
Study Overview
Status
Completed
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.
TAVT-18 is a novel formulation of sirolimus, an mTOR inhibitor.
This study evaluates TAVT-18 as 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 (Actual)
5
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital
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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
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 0-6 months of age at the time of enrollment (randomization and treatment initiation must occur before 7 months of age and infants born prematurely must have a corrected age of at least 39 weeks, calculated by subtracting the number of weeks born before 40 weeks gestation from the actual chronological age, in weeks)
- 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
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: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Stage 1 Open Label
Phase I/II, open-label PK and initial safety analysis.
TAVT-18 administered orally twice/daily to achieve precision dosing target of 10 ng/ml.
Whole blood sirolimus levels are assessed at defined intervals on days 1, 7, and 14.
After day 14, participants can elect to continue open-label treatment with TAVT-18 until 12 months of age.
Final developmental outcomes are assessed at 24 months of age.
|
The investigational drug product to be used in this study is TAVT-18, a proprietary formulation of sirolimus in clinical development, by Tavanta Therapeutics, Inc.
It is provided in a powder formulation in pre-measured vials.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
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12 months of age
|
Efficacy - time to seizure onset
Time Frame: 12 months of age
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Time from treatment initiation to seizure onset
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12 months of age
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment discontinuance due to adverse events
Time Frame: 12 months of age
|
Percentage of subjects that reduce or discontinue treatment due to an AE or SAE (any grade)
|
12 months of age
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Treatment disruption due to adverse events
Time Frame: 12 months of age
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Number of days treatment is withheld due to an AE or SAE (any grade).
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12 months of age
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Precision dosing accuracy
Time Frame: 12 months of age
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Blood trough concentration of sirolimus (ng/ml)
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12 months of age
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Age at seizure onset
Time Frame: 12 and 24 months of age
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Patient age in months at time of seizure onset
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12 and 24 months of age
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Seizure type
Time Frame: 12 and 24 months of age
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Percentage of subjects reporting infantile spasms, focal seizures, or other seizure types
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12 and 24 months of age
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Seizure frequency
Time Frame: 12 and 24 months of age
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Number of seizures in past 30 days
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12 and 24 months of age
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TAND severity assessed by the TAND-L Checklist
Time Frame: 12 and 24 months of age
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Overall severity rating on the TSC-associated Neuropsychiatric Disorders-Lifetime Version (TAND-L) Checklist.
The TAND-L Checklist severity rating ranges from 0-10, with higher values indicating greater concern.
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12 and 24 months of age
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Adaptive behavior assessed by the the VABS
Time Frame: 12 and 24 months of age
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Composite score on the Vineland Adaptive Behavior Scales (VABS).
The VABS composite score is normed to 100 = average or 50% percentile in normal populations, with lower values indicative of greater concern.
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12 and 24 months of age
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Global neurodevelopment assessed by the Bayley Scales of Infant Development
Time Frame: 12 and 24 months of age
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Composite score on the Bayley Scales of Infant Development.
The Bayley Scales of Infant Development is normed to 100 = average or 50% percentile in normal populations, with lower values indicative of greater concern.
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12 and 24 months of age
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Darcy Krueger, MD, PhD, Children's Hospital Medical Center, Cincinnati
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)
September 8, 2020
Primary Completion (Actual)
December 15, 2022
Study Completion (Actual)
December 15, 2022
Study Registration Dates
First Submitted
October 6, 2020
First Submitted That Met QC Criteria
October 19, 2020
First Posted (Actual)
October 20, 2020
Study Record Updates
Last Update Posted (Actual)
March 23, 2023
Last Update Submitted That Met QC Criteria
March 21, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- Heredodegenerative Disorders, Nervous System
- Neoplastic Syndromes, Hereditary
- Malformations of Cortical Development, Group I
- Malformations of Cortical Development
- Nervous System Malformations
- Neurocutaneous Syndromes
- Hamartoma
- Neoplasms, Multiple Primary
- Epilepsy
- Tuberous Sclerosis
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Sirolimus
Other Study ID Numbers
- 2019-1045
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
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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