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

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.

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

Study Overview

• Status: Active, not recruiting
• Conditions: Tuberous Sclerosis Complex
• Intervention / Treatment: Drug: everolimus

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.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2130
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Brussel
    • Jette, Brussel, Belgium, 1090
      • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Novartis Investigative Site
• Colombia
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760012
      • Novartis Investigative Site
• France
  • Amiens, France, 80054
    • Novartis Investigative Site
  • Bron Cedex, France, 69677
    • Novartis Investigative Site
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Marseille Cedex 05, France, 13885
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1145
    • Novartis Investigative Site
• Italy
  • BA
    • Bari, BA, Italy, 70124
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40139
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
  • SI
    • Siena, SI, Italy, 53100
      • Novartis Investigative Site
• Japan
  • Osaka, Japan, 534-0021
    • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • Suita, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Shizuoka
    • Shizuoka-city, Shizuoka, Japan, 420-8688
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 04 730
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 119991
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127412
    • Novartis Investigative Site
  • Samara Region
    • Samara, Samara Region, Russian Federation, 443095
      • Novartis Investigative Site
  • Voronezh Region
    • Voronezh, Voronezh Region, Russian Federation, 394024
      • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Pais Vasco
    • San Sebastian, Pais Vasco, Spain, 20080
      • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Novartis Investigative Site
  • Tainan, Taiwan, 70403
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06500
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
• United Kingdom
  • Buckinghamshire, United Kingdom, SL9 0RJ
    • Novartis Investigative Site
  • Liverpool, United Kingdom, L12 2AP
    • Novartis Investigative Site
  • London, United Kingdom, SW17 0QT
    • Novartis Investigative Site
  • London, United Kingdom, WC1N 3JH
    • Novartis Investigative Site
  • Sheffield, United Kingdom, S10 2TH
    • Novartis Investigative Site
  • York, United Kingdom, YO31 7EX
    • Novartis Investigative Site
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B15 2TH
      • Novartis Investigative Site
  • Cambrigdeshire
    • Cambridge, Cambrigdeshire, United Kingdom, CB2 0QQ
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90005-1752
      • Novartis Investigative Site
    • Oakland, California, United States, 94609
      • Novartis Investigative Site
    • San Diego, California, United States, 92123
      • Novartis Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novartis Investigative Site
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Novartis Investigative Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Novartis Investigative Site
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75219
      • Novartis Investigative Site
    • Houston, Texas, United States, 77030
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: everolimus; everolimus, 2mg dispersible tablets	Drug: everolimus; everolimus, 2mg dispersible tablets; Other Names: RAD001

What is the study measuring?

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,

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2017
• Primary Completion (Estimated): August 4, 2027
• Study Completion (Estimated): August 13, 2027

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimated): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Everolimus; TSC; PASS; Tuberous sclerosis complex; Long term safety; Refractory seizure; Roll over study
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Sclerosis; Seizures; Tuberous Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; MTOR Inhibitors; Everolimus
• Other Study ID Numbers: CRAD001M2X02B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No