Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
177
Countries
1
Sites
1
Refractory seizures associated with tuberous sclerosis complex
To evaluate long term safety data
Key facts
- Sponsor
- Novartis Pharma AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 30 Aug 2017 → 14 May 2025
- Decision date (initial)
- 2024-11-18
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2024-516746-19-00
- EudraCT number
- 2016-002977-37
- ClinicalTrials.gov
- NCT02962414
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others, Efficacy, Safety
To evaluate long term safety data
Secondary objectives 1
- To evaluate clinical benefit as assessed by the Investigator
Conditions and MedDRA coding
Refractory seizures associated with tuberous sclerosis complex
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | LLT | 10045138 | Tuberous sclerosis | 10010331 |
Regulatory references
- Plan to share IPD
- Yes
- IPD plan description
- Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations
| EU CT number | Title | Sponsor |
|---|---|---|
| 2011-000860-90 | A three-arm, randomized, double-blind, placebo-controlled study of the efficacy and safety of two trough-ranges of everolimus as adjunctive therapy in patients with tuberous sclerosis complex (TSC) who have refractory partial-onset seizures, Estudio doble ciego, aleatorizado, controlado con placebo, de tres brazos de tratamiento sobre la eficacia y seguridad de dos rangos de concentración valle de everolimus como tratamiento coadyuvante en pacientes con complejo de esclerosis tuberosa (CET) que presentan crisis convulsivas de inicio parciales refractarias, Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald., Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald., Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald., Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald., Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald., Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald., Et tre-armet, randomiseret, dobbeltblindt, placebo-kontrolleret klinisk forsøg til vurdering af effekt og sikkerhed ved to forskellige doser everolimus som supplerende behandling til patienter med Tuberøs Sklerosekompleks med vanskeligt kontrollerbare partielle anfald. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- 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.
- Willingness and ability to comply with scheduled visits and treatment plans
- Written informed consent/adolescent assent obtained prior to enrolling into the roll-over study
Exclusion criteria 5
- Patient has been permanently discontinued from everolimus study treatment in EXIST-3.
- Patient’s indication of TSC with refractory seizures is currently approved and reimbursed for everolimus in the local country
- Patients who are receiving everolimus in combination with unapproved or experimental treatments for seizure control (AEDs are allowed for the purpose of seizure control).
- Sexually active males, unless they use a condom during intercourse while taking drug and for 8 weeks after stopping study medication. Males also should not father a child in this period. A condom is also required to be used by vasectomized men to prevent delivery of the drug via seminal fluid
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Frequency and severity of AEs/SAEs
Secondary endpoints 1
- Proportion of patients with clinical benefit as assessed by the Investigator at scheduled visits
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB02065MIG · Substance
- Active substance
- Everolimus
- Pharmaceutical form
- DISPERSIBLE TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 36500 mg milligram(s)
- Max treatment duration
- 120 Month(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/10/764
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Novartis Pharma AG
- Sponsor organisation
- Novartis Pharma AG
- Address
- Lichtstrasse 35
- City
- Basel
- Postcode
- 4056
- Country
- Switzerland
Scientific contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Public contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Third parties 4
| Organisation | City, country | Duties |
|---|---|---|
| Q Squared Solutions Limited ORG-100042527
|
Livingston, United Kingdom | Other, Laboratory analysis, Code 5 |
| IQVIA Limited ORG-100008655
|
Reading, United Kingdom | On site monitoring, Interactive response technologies (IRT) |
| Xenobiotic Laboratories Inc. ORG-100012885
|
Plainsboro, United States | Other |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | Code 12 |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Poland | Ended | 2 | 1 |
| Rest of world
United Kingdom, Thailand, United States, Canada, Colombia, Turkey, Japan, Russian Federation, Australia, Korea, Republic of, Mexico, Taiwan
|
— | 175 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Poland | 2017-08-30 | 2025-05-14 | 2017-08-30 | 2018-03-09 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol - Signature Page_2024-516746-19-00_1_English_Red | 25Oct2016 |
| Protocol (for publication) | D1_Protocol_2024-516746-19-00_1_English_NonRed | 00 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements_Transition Replacement | 5.0 |
| Subject information and informed consent form (for publication) | L1_ICF - Adolescent Assent_1_PL_Polish_NonRed | 2 |
| Subject information and informed consent form (for publication) | L1_ICF - Child Assent_1_PL_Polish_NonRed | 1 |
| Subject information and informed consent form (for publication) | L1_ICF - Parent Legal Guardian_1_PL_Polish_NonRed | 2 |
| Subject information and informed consent form (for publication) | L1_ICF - Separate Data Protection Consent_1_PL_Polish_NonRed | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol - Protocol Summary in Technical Language_2024-516746-19-00_1_Polish_NonRed | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-25 | Poland | Acceptable 2024-11-14
|
2024-11-18 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-14 | Poland | Acceptable 2024-11-14
|
2025-02-14 |