Tuberous Sclerosis ComplexPhase 1/2STOP2NCT04595513

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

A Phase 1/2 study testing TAVT-18 (sirolimus) in people with Tuberous Sclerosis Complex and Epilepsy, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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). Read more about this study

Who is it for?: Ages 1 day to 6 months
Conditions the study is for: Tuberous Sclerosis Complex, Epilepsy
What is being tested?: TAVT-18 (sirolimus)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: 8 Sep 2020to 15 Dec 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 day to 6 months
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

Show all 9Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Cincinnati Children's Hospital
Cincinnati, Ohio, 45229

Other trials in United States

About this study

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).

Read the 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.

Conditions: Tuberous Sclerosis Complex, Epilepsy
Being tested: TAVT-18 (sirolimus)
Medical subject headings: Tuberous Sclerosis, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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.

Study groups in NCT04595513
Study group	Role	What they receive
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. Receives: Drug: TAVT-18 (sirolimus)

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety - Adverse Events
Percentage of subjects reporting severe (CTCAE v5.0 grade >= 3) adverse event (AE) or serious adverse event (SAE)
Measured: 12 months of age
Efficacy - Time to Seizure Onset
Time from treatment initiation to seizure onset
Measured: 12 months of age

Secondary outcomes (9)

Treatment Discontinuance Due to Adverse Events
Percentage of subjects that reduce or discontinue treatment due to an AE or SAE (any grade)
Measured: 12 months of age
Treatment Disruption Due to Adverse Events
Number of days treatment is withheld due to an AE or SAE (any grade).
Measured: 12 months of age
Precision Dosing Accuracy
Blood trough concentration of sirolimus (ng/ml)
Measured: 12 months of age
Age at Seizure Onset
Patient age in months at time of seizure onset
Measured: 12 and 24 months of age
Seizure Type
Percentage of subjects reporting infantile spasms, focal seizures, or other seizure types
Measured: 12 and 24 months of age
Seizure Frequency
Number of seizures in past 30 days
Measured: 12 and 24 months of age
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
Measured: 12 and 24 months of age
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
Measured: 12 and 24 months of age
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
Measured: 12 and 24 months of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Sep 202015 Dec 2022

First posted20 Oct 2020
Study start8 Sep 2020
Primary completion15 Dec 2022
Study completion15 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Tuberous Sclerosis ComplexStudies of the same condition, open and under way.
More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Model description: 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).
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04595513
Sponsor's protocol ID: 2019-1045
Acronym: STOP2
Status last verified: Apr 2024
First submitted: 6 Oct 2020
Last updated: 16 May 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

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.
PubMed 39331837

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 16 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants
ClinicalTrials.gov ID: NCT04595513
Acronym / sponsor ID: STOP2 / 2019-1045
Conditions: Tuberous Sclerosis Complex, Epilepsy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
Study start: 8 Sep 2020 (actual)
Primary completion: 15 Dec 2022 (actual)
Study completion: 15 Dec 2022 (actual)
First posted: 20 Oct 2020 (actual)
Results: Posted 16 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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).

Detailed description

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: 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).

Arm	Type	Receives
Stage 1 Open Label	Experimental	Drug: TAVT-18 (sirolimus)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.

Who may qualify

Ages: 1 day to 6 months
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (2 listed)

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

Key exclusion criteria (9 listed)

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)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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.	Drug	Stage 1 Open Label

Primary outcome

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)
Efficacy - Time to Seizure Onset
Time frame: 12 months of age
Time from treatment initiation to seizure onset

9 secondary outcomes

Treatment Discontinuance Due to Adverse Events
Time frame: 12 months of age
Treatment Disruption Due to Adverse Events
Time frame: 12 months of age
Precision Dosing Accuracy
Time frame: 12 months of age
Age at Seizure Onset
Time frame: 12 and 24 months of age
Seizure Type
Time frame: 12 and 24 months of age
Seizure Frequency
Time frame: 12 and 24 months of age
TAND Severity Assessed by the TAND-L Checklist
Time frame: 12 and 24 months of age
Adaptive Behavior Assessed by the the VABS
Time frame: 12 and 24 months of age
Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
Time frame: 12 and 24 months of age

Results and safety

Results posted to the registry on 16 May 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Stage 1 Open Label	5	5

Primary outcome: Safety - Adverse Events

Time frame: 12 months of age. Number. Unit: percentage of participants

Measure	Stage 1 Open Label n = 5
Value	40

Primary outcome: Efficacy - Time to Seizure Onset

Time frame: 12 months of age. Median (Full Range). Unit: days

Measure	Stage 1 Open Label n = 2
Value	102 (26 to 178)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months of Age. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stage 1 Open Label	0 of 5 (0%)	5 of 5 (100%)	0 of 5

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 39331837Masuda 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Darcy Krueger, MD, PhD principal investigator

Children's Hospital Medical Center, Cincinnati

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TAVT-18 (sirolimus) in people with Tuberous Sclerosis Complex and Epilepsy, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety - Adverse Events (time frame: 12 months of age). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04595513, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2024.