Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With Tuberous Sclerosis Complex

Multicenter, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Rapamycin in Drug Resistant Epilepsy Associated With TSC

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).

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).

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