Trial Outcomes & Findings for Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants (NCT NCT04595513)
NCT ID: NCT04595513
Last Updated: 2024-05-16
Results Overview
Percentage of subjects reporting severe (CTCAE v5.0 grade \>= 3) adverse event (AE) or serious adverse event (SAE)
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
5 participants
Primary outcome timeframe
12 months of age
Results posted on
2024-05-16
Participant Flow
Five participants were screened; all five were eligible for enrollment.
Participant milestones
| Measure |
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.
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.
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|---|---|
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Overall Study
STARTED
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5
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Overall Study
COMPLETED
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5
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Stopping TSC Onset and Progression 2: Epilepsy Prevention in TSC Infants
Baseline characteristics by cohort
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Age, Categorical
<=18 years
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5 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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0 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age, Continuous
|
2.0 months
n=5 Participants
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Sex: Female, Male
Female
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4 Participants
n=5 Participants
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Sex: Female, Male
Male
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1 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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1 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
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5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Region of Enrollment
United States
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5 participants
n=5 Participants
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PRIMARY outcome
Timeframe: 12 months of agePercentage of subjects reporting severe (CTCAE v5.0 grade \>= 3) adverse event (AE) or serious adverse event (SAE)
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Safety - Adverse Events
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40 percentage of participants
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PRIMARY outcome
Timeframe: 12 months of ageTime from treatment initiation to seizure onset
Outcome measures
| Measure |
Stage 1 Open Label
n=2 Participants
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.
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|---|---|
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Efficacy - Time to Seizure Onset
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102 days
Interval 26.0 to 178.0
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SECONDARY outcome
Timeframe: 12 months of agePercentage of subjects that reduce or discontinue treatment due to an AE or SAE (any grade)
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Treatment Discontinuance Due to Adverse Events
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20 percentage of participants
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SECONDARY outcome
Timeframe: 12 months of ageNumber of days treatment is withheld due to an AE or SAE (any grade).
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Treatment Disruption Due to Adverse Events
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19.5 days
Interval 0.0 to 54.0
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SECONDARY outcome
Timeframe: 12 months of ageBlood trough concentration of sirolimus (ng/ml)
Outcome measures
| Measure |
Stage 1 Open Label
n=4 Participants
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.
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|---|---|
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Precision Dosing Accuracy
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6.6 ng/mL
Interval 3.6 to 9.3
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SECONDARY outcome
Timeframe: 12 and 24 months of agePatient age in months at time of seizure onset
Outcome measures
| Measure |
Stage 1 Open Label
n=3 Participants
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.
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|---|---|
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Age at Seizure Onset
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10.6 months
Interval 2.9 to 19.7
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SECONDARY outcome
Timeframe: 12 and 24 months of agePopulation: Five participants were enrolled in the study. Only three of the enrolled participants developed seizures during the course of the study.
Percentage of subjects reporting infantile spasms, focal seizures, or other seizure types
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Seizure Type
12 months of Age -- Infantile Spasms
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40 percentage of participants
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Seizure Type
12 months of Age -- Focal Seizures
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20 percentage of participants
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Seizure Type
24 months of Age -- Infantile Spasms
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40 percentage of participants
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Seizure Type
24 months of Age -- Focal Seizures
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60 percentage of participants
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SECONDARY outcome
Timeframe: 12 and 24 months of agePopulation: Five participants were enrolled in the study. Only three of the enrolled participants developed seizures during the course of the study.
Number of seizures in past 30 days
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Seizure Frequency
12 months of Age
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0 seizures
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Seizure Frequency
24 months of Age
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0 seizures
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SECONDARY outcome
Timeframe: 12 and 24 months of agePopulation: All participants completed the assessment at 12 months of age. One participant was unable to complete the assessment at the 24 month timepoint.
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
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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TAND Severity Assessed by the TAND-L Checklist
12 months of Age -- Parent Rating
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2 units on a scale (0 - 10)
Interval 0.0 to 5.0
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TAND Severity Assessed by the TAND-L Checklist
12 months of Age -- Clinician Rating
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2 units on a scale (0 - 10)
Interval 0.0 to 5.0
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TAND Severity Assessed by the TAND-L Checklist
24 months of Age -- Parent Rating
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1 units on a scale (0 - 10)
Interval 0.0 to 2.0
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TAND Severity Assessed by the TAND-L Checklist
24 months of Age -- Clinician Rating
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3.5 units on a scale (0 - 10)
Interval 0.0 to 4.0
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SECONDARY outcome
Timeframe: 12 and 24 months of ageComposite 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
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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Adaptive Behavior Assessed by the the VABS
12 months of Age -- Adaptive Behavior Composite Score
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91 composite score
Interval 86.0 to 102.0
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Adaptive Behavior Assessed by the the VABS
24 months of age -- Adaptive Behavior Composite Score
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88 composite score
Interval 68.0 to 128.0
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SECONDARY outcome
Timeframe: 12 and 24 months of agePopulation: 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.
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
Outcome measures
| Measure |
Stage 1 Open Label
n=5 Participants
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.
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|---|---|
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Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
12 months of Age -- Cognitive Domain
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90 composite score
Interval 70.0 to 110.0
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Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
12 months of Age -- Language Domain
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89 composite score
Interval 75.0 to 100.0
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Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
12 months of Age -- Motor Domain
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87 composite score
Interval 72.0 to 112.0
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Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
24 months of Age -- Cognitive Domain
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95 composite score
Interval 70.0 to 100.0
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Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
24 months of Age -- Language Domain
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77 composite score
Interval 70.0 to 92.0
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Global Neurodevelopment Assessed by the Bayley Scales of Infant Development
24 months of Age -- Motor Domain
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74 composite score
Interval 74.0 to 87.0
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Adverse Events
Stage 1 Open Label
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Stage 1 Open Label
n=5 participants at risk
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.
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Gastrointestinal disorders
Constipation
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40.0%
2/5 • Number of events 4 • 12 months of Age
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Gastrointestinal disorders
Excessive Flatulence
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40.0%
2/5 • Number of events 4 • 12 months of Age
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Gastrointestinal disorders
Emesis (vomiting)
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20.0%
1/5 • Number of events 5 • 12 months of Age
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Gastrointestinal disorders
Hematochezia (Bloody stool)
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Gastrointestinal disorders
Diarrhea
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Gastrointestinal disorders
Stomatitis (mouth sores/ulcers)
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40.0%
2/5 • Number of events 5 • 12 months of Age
|
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General disorders
Pyrexia (fever)
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40.0%
2/5 • Number of events 8 • 12 months of Age
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General disorders
Fussiness
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20.0%
1/5 • Number of events 13 • 12 months of Age
|
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General disorders
Discomfort/Pain due to Teething
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20.0%
1/5 • Number of events 3 • 12 months of Age
|
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General disorders
Fatigue
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Immune system disorders
Rash (Allergic reaction)
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Infections and infestations
Rhinitis
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60.0%
3/5 • Number of events 4 • 12 months of Age
|
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Infections and infestations
Otitis Media
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60.0%
3/5 • Number of events 3 • 12 months of Age
|
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Infections and infestations
Rhinosinusitis (Sinus infection)
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Infections and infestations
Abscess w/Infection
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Infections and infestations
Croup w/Stridor
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Infections and infestations
Respiratory Syncytial Virus (RSV)
|
20.0%
1/5 • Number of events 1 • 12 months of Age
|
|
Infections and infestations
Hand-Foot-Mouth Disease
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20.0%
1/5 • Number of events 1 • 12 months of Age
|
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Metabolism and nutrition disorders
Hypertriglyceridemia
|
80.0%
4/5 • Number of events 4 • 12 months of Age
|
|
Metabolism and nutrition disorders
Hypercholesterolemia
|
60.0%
3/5 • Number of events 4 • 12 months of Age
|
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Psychiatric disorders
Insomnia
|
40.0%
2/5 • Number of events 2 • 12 months of Age
|
|
Respiratory, thoracic and mediastinal disorders
Tussis (cough)
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60.0%
3/5 • Number of events 3 • 12 months of Age
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea (Congestion)
|
40.0%
2/5 • Number of events 8 • 12 months of Age
|
|
Skin and subcutaneous tissue disorders
Lip Lesion
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20.0%
1/5 • Number of events 4 • 12 months of Age
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
20.0%
1/5 • Number of events 5 • 12 months of Age
|
|
Skin and subcutaneous tissue disorders
Eczema
|
20.0%
1/5 • Number of events 2 • 12 months of Age
|
|
Vascular disorders
Hypertension
|
20.0%
1/5 • Number of events 1 • 12 months of Age
|
Additional Information
Darcy A. Krueger, MD., PhD
Cincinnati Children's Hospital Medical Center
Phone: 513-636-4222
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place