Clinical trial NCT02962414: 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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Tuberous Sclerosis Complex
Keywords: Everolimus
Tuberous sclerosis complex
TSC
Refractory seizure
Roll over study
Long term safety
PASS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-11-11
Enrollment: 206
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurances of adverse events and serious adverse events
timeFrame: Day 1 up to approximately 10 years
Secondary outcomes:
measure: Percentage of patients with clinical benefit
timeFrame: Day 1 up to approximately 10 years, assessed every 12 weeks,
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: TGen APNNA
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children s Hospital
state: California
city: San Diego
country: United States
facility: Rady Children s Hospital
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Hartford
country: United States
facility: Connecticut Childrens Medical Cntr
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Saint Paul
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: Morristown
country: United States
facility: Atlantic Health Systems
state: New Jersey
city: Cincinnati
country: United States
facility: Cinn Children Hosp Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Scottish Rite Hos for Child
state: Texas
city: Houston
country: United States
facility: Texas Childrens Hospital
state: Texas
city: Randwick
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Cali
country: Colombia
facility: Novartis Investigative Site
state: Valle Del Cauca
city: Amiens
country: France
facility: Novartis Investigative Site
city: Bron Cedex
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Suita
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Shizuoka-city
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Samara
country: Russian Federation
facility: Novartis Investigative Site
state: Samara Region
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Voronezh
country: Russian Federation
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Buckinghamshire
country: United Kingdom
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
city: York
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: