Nervous System Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Epilepsy

Sclerosis

Disease Progression

Tuberous Sclerosis

Brain Diseases

Central Nervous System Diseases

Hamartoma

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Congenital Abnormalities

Malformations of Cortical Development

Nervous System Malformations

Neurocutaneous Syndromes

Heredodegenerative Disorders, Nervous System

Neurodegenerative Diseases

Genetic Diseases, Inborn

Tuberous Sclerosis Complex

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Dermatologic Agents

Tin Fluorides

Sirolimus

Coal Tar

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

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.

TAVT-18 (sirolimus)

Darcy Krueger, MD, PhD

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).

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.

This trial is a single stage, phase I/II clinical trial design. Treatment is open-label to verify safety and dosing for TAVT-18 in TSC infants.

Note that this clinical trial originally planned for a follow-up second stage employing a randomized, double-blind, placebo-controlled multisite design. In October 2021, the second stage of this study was replaced by the TSC-STEPS clinical trial (clinicaltrials.gov NCT05104983).

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

Percentage of subjects reporting severe (CTCAE v5.0 grade \>= 3) adverse event (AE) or serious adverse event (SAE)

Time from treatment initiation to seizure onset

Percentage of subjects that reduce or discontinue treatment due to an AE or SAE (any grade)

Number of days treatment is withheld due to an AE or SAE (any grade).

Blood trough concentration of sirolimus (ng/ml)

Patient age in months at time of seizure onset

Percentage of subjects reporting infantile spasms, focal seizures, or other seizure types

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

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

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

Children's Hospital Medical Center, Cincinnati

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.

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.

Stage 1 Open Label

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Primary endpoints and universal treatment by study design continued through 12 months. Between 12-24 months, ongoing treatment with sirolimus was optional. In this study, 4/5 participants elected to continue sirolimus treatment through the secondary 24 month timepoint.

Darcy A. Krueger, MD., PhD

Safety - Adverse Events

Efficacy - Time to Seizure Onset

Treatment Discontinuance Due to Adverse Events

Treatment Disruption Due to Adverse Events

Precision Dosing Accuracy

Age at Seizure Onset

12 months of Age -- Infantile Spasms

12 months of Age -- Focal Seizures

24 months of Age -- Infantile Spasms

24 months of Age -- Focal Seizures

Five participants were enrolled in the study. Only three of the enrolled participants developed seizures during the course of the study.

Seizure Type

12 months of Age

24 months of Age

Seizure Frequency

12 months of Age -- Parent Rating

12 months of Age -- Clinician Rating

24 months of Age -- Parent Rating

24 months of Age -- Clinician Rating

All participants completed the assessment at 12 months of age. One participant was unable to complete the assessment at the 24 month timepoint.

TAND Severity Assessed by the TAND-L Checklist

12 months of Age -- Adaptive Behavior Composite Score

24 months of age -- Adaptive Behavior Composite Score

Adaptive Behavior Assessed by the the VABS

12 months of Age -- Cognitive Domain

12 months of Age -- Language Domain

12 months of Age -- Motor Domain

24 months of Age -- Cognitive Domain

24 months of Age -- Language Domain

24 months of Age -- Motor Domain

24 months of Age: Cognitive Domain only four of five participants completed this assessment as one participant became ill during visit. Language and Motor Domains only three of five participants completed these assessments as one became ill during visit and one participant became non-compliant during testing.

Global Neurodevelopment Assessed by the Bayley Scales of Infant Development

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.

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.

Spots Global Cancer Trial Database for Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial