Roll-over Study to Collect and Assess Long-term Safety of Everolimus in Patients With TSC and Refractory Seizures Who Have Completed the EXIST-3 Study [CRAD001M2304] and Who Are Benefitting From Continued Treatment

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety in patients with TSC and refractory seizures who are currently receiving everolimus treatment in the Novartis-sponsored EXIST-3 study and who are determined to be benefiting from continued treatment as judged by the investigator at the completion of EXIST-3

Detailed Description
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This is a multi-center, open label study to evaluate the long term safety of everolimus in patients with TSC and refractory seizures currently being treated in the Novartis-sponsored study EXIST-3 study and are judged by their parent study investigator as benefiting from the current study treatment. The study is expected to remain open for approximately 10 years (or until 31-Dec-2022 in the UK) from First Patient First Visit (FPFV). Patients will continue to be treated in this study until they are no longer benefiting from their everolimus treatment as judged by the Investigator or until one of the protocol defined discontinuation criteria is met or everolimus becomes commercially available according to local regulations.

Official Title
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An Open-label, Multi-center Long-term Safety Roll-over Study in Patients With Tuberous Sclerosis Complex (TSC) and Refractory Seizures Who Are Judged by the Investigator to Benefit From Continued Treatment With Everolimus After Completion of Study CRAD001M2304.

Conditions
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Tuberous Sclerosis Complex

Intervention / Treatment
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* Drug: everolimus


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patient is currently enrolled in the Novartis-sponsored EXIST-3 study, receiving everolimus, and has fulfilled all its requirements Patient is currently benefiting from treatment with everolimus, as determined by the Investigator. Patient has demonstrated compliance, as assessed by the Investigator,with the parent study protocol requirements. Patient is willing and able to comply with scheduled visits and treatment plans. Written informed consent/adolescent assent obtained prior to enrolling into the roll-over study. Key Exclusion Criteria: Patient has been permanently discontinued from everolimus study treatment in EXIST-3 study Everolimus is approved for patients with TSC and refractory seizures and is reimbursed in the local country. Patients who are receiving everolimus in combination with unapproved or experimental treatments for seizure control Anti-epileptic drug (AEDs) are allowed for the purpose of seizure control.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: everolimus<br>everolimus, 2mg dispersible tablets | Drug: everolimus<br>* everolimus, 2mg dispersible tablets<br>* Other names: RAD001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurances of adverse events and serious adverse events | The patients will be followed continuously for tolerability (i.e adverse events, serious adverse events) | Day 1 up to approximately 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with clinical benefit | At every quarterly visit (every 12 weeks ± 2 weeks), the Investigator is required to confirm that the patients continue to have clinical benefit as per Investigator's assessment. | Day 1 up to approximately 10 years, assessed every 12 weeks, | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Everolimus, Tuberous sclerosis complex, TSC, Refractory seizure, Roll over study, Long term safety, PASS