Clinical trial NCT05534672: Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With Tuberous Sclerosis Complex
Official title: Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With TSC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Tuberous Sclerosis Complex
Keywords: tuberous sclerosis complex, epilepsy, rapamycin, drug resistant epilepsy
Lead sponsor: Children's Memorial Health Institute, Poland
Sponsor class: OTHER
First posted: 2022-09-09
Enrollment: 200
Sex: ALL
Minimum age (years): 3
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the RaRE-TS study is to determine safety, tolerability and efficacy of rapamycin versus placebo in a drug resistant epilepsy associated with tuberous sclerosis complex (TSC).

Detailed description: This is a two-arm, randomized, double-blind, placebo controlled study to evaluate the efficacy, tolerability, and safety of rapamycin versus placebo in a drug resistant epilepsy associated with TSC. The study consists of 3 phases for each patient: screening, dose adjustment blinded phase, core blinded phase, followed by open-label observation. Patients who meet the eligibility criteria will be randomized to receive rapamycin or placebo. The randomization ratio is 1:1. Randomization will be stratified by age, sex and and the number of antiepileptic drugs ever used in the patient's history (up to 3 drugs / more than 3 drugs).

Eligibility criteria: Inclusion Criteria:

* male or female aged from 3 months up to 50 years at the day of randomization
* patients/parents/caregivers are willing to and able to give informed consent form for the participation in the study
* patients/parents/caregivers are willing to and able to comply with all study requirements
* definite diagnosis of TSC according to the Consensus criteria (Northrup, 2013)
* drug-resistant epilepsy associated with TSC with at least 8 seizures during 4 weeks

Exclusion Criteria:

* history of treatment with mTOR inhibitor in the three months prior to screening,
* history of pseudo-epileptic seizures,
* history of progressive CNS disease other than TSC
* recent surgery within 2 weeks prior to the screening
* severe infection within 2 weeks prior to the screening
* use of the cannabis derivatives
* contraindications for MRI or general anesthesia
* occurrence of the serious comorbidities 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 the investigator
* pregnancy

Primary outcomes:
measure: comparison of the number of patients with at least 50% reduction of seizures per week in the last month of the core blinded phase in comparison to screening phase in the rapamycin vs placebo group
timeFrame: final analyses after the formal final database lock, planned within one month after the last patient last visit in the study
measure: number of adverse events (according to CTCAE classification) in the rapamycin vs placebo group during the double-blind core phase
timeFrame: final analyses after the formal final database lock, planned within one month after the last patient last visit in the study
Secondary outcomes:
measure: comparison of the number of seizures per week and the number of days free of seizures in the rapamycin vs placebo group, during 12-week treatment in double-blind core phase
timeFrame: final analyses after the formal final database lock, planned within one month after the last patient last visit in the study
measure: severity of adverse events (according to CTCAE) and the number of patients withdrawn from the study due to adverse events in the rapamycin vs placebo group
timeFrame: final analyses after the formal final database lock, planned within one month after the last patient last visit in the study
Other outcomes:
Locations:
city: Lodz
country: Poland
facility: Medical University of Lodz
city: Warsaw
country: Poland
facility: Children's Memorial Health Institute, Neurology and Epileptology
Study officials:
References: