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

NCT04595513 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2019-1045
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Tuberous Sclerosis Complex; Epilepsy

Outcome Measures

Primary Outcomes (2)

• 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

• Efficacy - Time to Seizure Onset

  Time from treatment initiation to seizure onset

  12 months of age

Secondary Outcomes (9)

• Treatment Discontinuance Due to Adverse Events

  12 months of age

• Treatment Disruption Due to Adverse Events

  12 months of age

• Precision Dosing Accuracy

  12 months of age

• Age at Seizure Onset

  12 and 24 months of age

• Seizure Type

  12 and 24 months of age

Study Arms (1)

Stage 1 Open Label

EXPERIMENTAL

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.

Drug: TAVT-18 (sirolimus)

Interventions

TAVT-18 (sirolimus) DRUG

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

Eligibility Criteria

• Age: 1 Day - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

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

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• Masuda S, Lemaitre F, Barten MJ, Bergan S, Shipkova M, van Gelder T, Vinks S, Wieland E, Bornemann-Kolatzki K, Brunet M, de Winter B, Dieterlen MT, Elens L, Ito T, Johnson-Davis K, Kunicki PK, Lawson R, Lloberas N, Marquet P, Millan O, Mizuno T, Moes DJAR, Noceti O, Oellerich M, Pattanaik S, Pawinski T, Seger C, van Schaik R, Venkataramanan R, Walson P, Woillard JB, Langman LJ. Everolimus Personalized Therapy: Second Consensus Report by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Ther Drug Monit. 2025 Feb 1;47(1):4-31. doi: 10.1097/FTD.0000000000001250. Epub 2024 Sep 25.

  PMID: 39331837 DERIVED

MeSH Terms

Conditions

Tuberous Sclerosis; Epilepsy

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

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.

Results Point of Contact

• Title: Darcy A. Krueger, MD., PhD
• Organization: Cincinnati Children's Hospital Medical Center

krueger_darcy@cchmc.org

513-636-4222

Study Officials

• Darcy Krueger, MD, PhD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 20, 2020
• Study Start: September 8, 2020
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: May 16, 2024
• Results First Posted: May 16, 2024

Record last verified: 2024-04

Locations

US (1)