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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Tuberous Sclerosis Complex

Intervention / Treatment
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* Other: Rapamycin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin arm<br>Each patient randomized to the rapamycin arm will receive rapamycin in liquid. The rapamycin will be administered in individually calculated doses depending on the body surface of participants | Other: Rapamycin<br>* Rapamycin in liquid administered orally<br>|
| Placebo Comparator: Placebo arm<br>The patients assigned to the placebo arm will receive placebo in liquid, analogically to the rapamycin group. | Other: Placebo<br>* Placebo in liquid administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | final analyses after the formal final database lock, planned within one month after the last patient last visit in the study | 
| number of adverse events (according to CTCAE classification) in the rapamycin vs placebo group during the double-blind core phase |  | final analyses after the formal final database lock, planned within one month after the last patient last visit in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | final analyses after the formal final database lock, planned within one month after the last patient last visit in the study | 
| 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 |  | final analyses after the formal final database lock, planned within one month after the last patient last visit in the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tuberous sclerosis complex, epilepsy, rapamycin, drug resistant epilepsy