Clinical trial NCT04987463: Efficacy and Safety of Rapamycin Versus Vigabatrin in the Prevention of Tuberous Sclerosis Complex Symptoms in Infants
Official title: Randomized, Placebo-controlled, Double-blind and Double-dummy Clinical Trial Comparing the Safety, Tolerability, and Efficacy of Vigabatrin and Rapamycin in a Preventive Treatment of Infants With Tuberous Sclerosis Complex
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Tuberous Sclerosis Complex
Keywords: tuberous sclerosis complex, epilepsy, rapamycin, vigabatrin, tumors, prevention
Lead sponsor: Children's Memorial Health Institute, Poland
Sponsor class: OTHER
First posted: 2021-08-03
Enrollment: 60
Sex: ALL
Minimum age (years): 4
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to evaluate the efficacy, tolerability, and safety of vigabatrin versus rapamycin as a preventive treatment in infants with Tuberous Sclerosis Complex (TSC).

Detailed description: This is a two-arm, randomized, double-blind and double-dummy, placebo controlled study to evaluate the efficacy, tolerability, and safety of vigabatrin versus rapamycin as a preventive treatment in infants with TSC. The study consists of 3 phases for each patient: screening, core blinded phase, and open-label follow-up phase. Patients who meet the eligibility criteria will be randomized to receive vigabatrin or rapamycin. The randomization ratio is 1:1. Randomization will be stratified by the sex and the presence of epileptiform activity on baseline videoEEG (video electroencephalography) recording (yes versus no). Approximately 60 infants are planned to be enrolled in the study.

Eligibility criteria: Inclusion Criteria:

* Male or female aged from 4 up to 16 weeks (44-56 weeks of gestational age) at the day of randomization
* Parents/caregivers are willing to and able to give informed consent form for the participation in the study
* Parents/caregivers are willing to and able to comply with all study requirements
* Definite diagnosis of TSC according to the Consensus criteria (Northrup,2013)
* At least 1 focus of cortical dysplasia disclosed on brain MRI

Exclusion Criteria:

* history of seizures prior to randomization,
* history of antiepileptic treatment,
* history of treatment with mTOR (mammalian Target of Rapamycin) inhibitor,
* gestational age below 44 weeks at the day of randomization,
* body weight lower than 3 kg at the day of randomization,
* SEGA (Subependymal Giant Cell Astrocytoma) or other TSC-associated lesion requiring urgent surgical intervention
* recent surgery within 1 month prior to the randomization
* intercurrent infection at the date of randomization
* known history of HIV seropositivity
* live vaccination within 1 month prior to randomization\*
* lack of first TBC and hepatitis B vaccinations
* Any significant clinical, laboratory , ECG or other abnormalities, comorbidity or concomitant treatment which, in the opinion of the investigator, may either put a patient at significant risk associated with the participation in the study or may influence the results of the study.
* Use of an investigational drug within 1 month prior to randomization.

Primary outcomes:
measure: Occurrence of clinical seizures in the blinded phase of the study,
timeFrame: 730 days
measure: Summarized volume of TSC-associated tumors ≥ 125% of initial value within the blinded phase of the study
timeFrame: 730 days
Secondary outcomes:
measure: Total volume of TSC-associated tumors within the blinded phase and the whole study
timeFrame: 730 days
measure: The risk for high risk of autism assessed with psychological test at 6, 12, 18, 24 months
timeFrame: 6, 12, 18, 24 months
measure: The risk for low developmental quotient (< 70 points in Bayley Scales of Infant Development, measured at the end of the blinded phase and at the end of the entire study) at the end of the study
timeFrame: 730 days
measure: The risk of drug-resistant epilepsy at any point of the study
timeFrame: 730 days
measure: Occurrence of adverse events within the blinded phase of the study
timeFrame: 730 days
measure: Number of adverse events across the whole study
timeFrame: 730 days
measure: Parameters of physical development (weight gain history) across the whole study
timeFrame: 730 days
measure: Parameters of physical development (height gain history) across the whole study
timeFrame: 730 days
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Medical University of Warsaw, Department of Pediatric Neurology
city: Warsaw
country: Poland
facility: Children's Memorial Health Institute, Neurology and Epileptology
Study officials:
affiliation: The Children's Memorial Health Institute
name: Katarzyna Kotulska-Jozwiak
role: PRINCIPAL_INVESTIGATOR
References: