Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants

Epilepsy Clinical Trial

— STOP2  

Official title:

Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04595513
• Other study ID #: 2019-1045
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 8, 2020
• Est. completion date: December 15, 2022

Study information

• Verified date: April 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: December 15, 2022
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 6 Months

Eligibility

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

Related Conditions & MeSH terms

• Epilepsy
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Intervention

Drug:
• TAVT-18 (sirolimus)
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.

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety - Adverse Events	Percentage of subjects reporting severe (CTCAE v5.0 grade >= 3) adverse event (AE) or serious adverse event (SAE)	12 months of age
Primary	Efficacy - Time to Seizure Onset	Time from treatment initiation to seizure onset	12 months of age
Secondary	Treatment Discontinuance Due to Adverse Events	Percentage of subjects that reduce or discontinue treatment due to an AE or SAE (any grade)	12 months of age
Secondary	Treatment Disruption Due to Adverse Events	Number of days treatment is withheld due to an AE or SAE (any grade).	12 months of age
Secondary	Precision Dosing Accuracy	Blood trough concentration of sirolimus (ng/ml)	12 months of age
Secondary	Age at Seizure Onset	Patient age in months at time of seizure onset	12 and 24 months of age
Secondary	Seizure Type	Percentage of subjects reporting infantile spasms, focal seizures, or other seizure types	12 and 24 months of age
Secondary	Seizure Frequency	Number of seizures in past 30 days	12 and 24 months of age
Secondary	TAND Severity Assessed by the TAND-L Checklist	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.; Parent Rating: "Considering all of the issues reported today how much have these bothered, troubled, or distressed you/your child/family?"; Min = 0 Max = 10; higher values indicate greater concern.; Clinician Rating: "Interviewer's judgement of impact/burden on the individual/child/family."; Min = 0 Max = 10; higher values indicate greater concern	12 and 24 months of age
Secondary	Adaptive Behavior Assessed by the the VABS	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.; Adaptive Scale: Minimum = 20, Maximum = 140, Standard deviation is +/- 15	12 and 24 months of age
Secondary	Global Neurodevelopment Assessed by the Bayley Scales of Infant Development	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.; Cognitive Domain: Minimum = 40, Maximum = 160, Standard Deviation is +/- 15 Language Domain: Minimum = 40, Maximum = 160, Standard Deviation is +/- 15 Motor Doman: Minimum = 40, Maximum = 160, Standard Deviation is +/- 15	12 and 24 months of age