Tuberous Sclerosis Complex (TSC)Phase 3EXIST-2NCT00790400
Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
A Phase 3 study testing Everolimus (RAD001) in people with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM), run by Novartis Pharmaceuticals at 25 sites in 11 countries.
Trial summary
This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberous Sclerosis Complex (TSC), Lymphangioleiomyomatosis (LAM)
- What is being tested?
- Everolimus (RAD001)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 25 sitesin 11 countries
- Study dates
- Apr 2009to Nov 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or Female 18 years or older
- Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)
- Clinically definite diagnosis of renal angiomyolipoma
- At least one Angiomyolipoma of ≥ 3 cm in its longest diameter using CT or MRI
- Females of child bearing potential must use birth control and have documentation of negative pregnancy test
- Written informed consent according to local guidelines
Who cannot join
- Recent heart attack, cardiac related chest pain or stroke
- Severely impaired lung function
- Bleeding related to angiomyolipoma or embolization during 6 months prior to randomization
- Clinically significant chylous ascites
- Clinically significant hematological or hepatic abnormality
- Severe liver dysfunction
Show all 22Show fewer
- Severe kidney dysfunction
- Pregnancy or breast feeding
- Current infection
- History of organ transplant
- Surgery within two months prior to study enrollment
- Prior therapy with a medication in the same class as Everolimus
- Recent use of an investigational drug
- Bleeding diathesis or on oral anti-vitamin K medication
- Uncontrolled high cholesterol
- Uncontrolled diabetes
- HIV
- Inability to attend scheduled clinic visits
- Patients with metal implants thus prohibiting MRI evaluations
- Angiomyolipoma which requires surgery at the time of randomization
- History of malignancy
- Severe or uncontrolled medical conditions which would cause an unacceptable safety risk or compromise compliance with the protocol
Trial locations and contacts
25 sites in 11 countries.
25 sites in 11 countries
United States6 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital Massachussetts General Hospita
Boston, Massachusetts, 02114
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
LeBonheur Childrens Medical Group SC-2
Memphis, Tennessee, 38103
Barrow Tuberous Sclerosis Center
Phoenix, Arizona, 85013
Minnesota Epilepsy Group
Saint Paul, Minnesota, 55102-2383
United Kingdom4 sites
Novartis Investigative Site
Brighton, East Sussex, BN2 5BE
Novartis Investigative Site
Cardiff, Wales, CF14 4XN
Novartis Investigative Site
Craigavon, Northern Ireland, BT63 5QQ
Novartis Investigative Site
London, SW17 0QT
Italy3 sites
Novartis Investigative Site
Roma, 00137
Novartis Investigative Site
Siena, SI, 53100
Novartis Investigative Site
Torino, TO, 10126
Japan3 sites
Novartis Investigative Site
Sapporo, Hokkaido, 060-8648
Novartis Investigative Site
Suita, Osaka, 565-0871
Novartis Investigative Site
Yamagata, Yamagata, 990-9585
Germany2 sites
Novartis Investigative Site
Berlin, 10098
Novartis Investigative Site
München, 80336
Poland2 sites
Novartis Investigative Site
Warsaw, 01138
Novartis Investigative Site
Warsaw, 04-730
Netherlands1 site
Novartis Investigative Site
Utrecht, Netherlands, 3584CX
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis.
- Being tested
- Everolimus (RAD001), Everolimus Placebo
- Keywords
- Angiomyolipoma, AML, Tuberous Sclerosis Complex, TSC, mTOR, RAD001, Mammalian Target of Rapamycin, Everolimus, Afinitor, SEGA, Subependymal Giant Cell Astrocytoma, Seizures, Tuberous sclerosis complex (TSC), Tuberous sclerosis, benign tumors of brain, kidney, heart, eyes, lungs, skinTSC1
- Medical subject headings
- Tuberous Sclerosis, Lymphangioleiomyomatosis, Angiomyolipoma, Hereditary Sensory and Autonomic Neuropathies, Astrocytoma, Seizures, Tuberous Sclerosis 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus (RAD001)Drug
Also called RAD001
Everolimus is used in 5 mg strength tablets, blister-packed under aluminum foil in units of ten tablets and dosed on a daily basis. 10mg daily dosing throughout the trial.
Everolimus PlaceboDrug
Matching placebo was provided as a matching tablet and was also blister-packed under aluminum foil in units of ten.
| Study group | Role | What they receive |
|---|---|---|
| Everolimus | Experimental | Study drug was given by continuous oral daily dosing of two 5 mg tablets. Receives: Drug: Everolimus (RAD001) |
| Placebo | Placebo comparator | Placebo was given by continuous oral daily dosing of two 5 mg tablets. Receives: Drug: Everolimus Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Angiomyolipoma Response Rate as Per Central Radiology Review
Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2.
For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
Measured: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Secondary outcomes (9)
Time to Angiomyolipoma Progression as Per Central Radiology Review
Time to angiomyolipoma progression (TTAP) is defined as time from date of randomization to date of first documented angiomyolipoma progression. Angiomyolipoma progression was defined as one or more of the following: Increase from nadir of ≥ 25% in angiomyolipoma volume to value greater than baseline; the appearance of a new angiomyolipoma ≥ 1.0 cm in longest diameter; an increase from nadir of 20% or more in the volume of either kidney to a value greater than baseline; angiomyolipoma-related bleeding grade ≥ 2.
For the everolimus (core/extension periods) treatment group, the time to angiomyolipoma progression is defined starting from the start of everolimus. The baseline means the latest value on or before starting everolimus.
Measured: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years
Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)
Skin lesion response rate in the double-blind period was determined only among patients with at least one skin lesion at baseline, and is the percentage of this group of patients with a best overall skin lesion response on the Physician's Global Assessment of Clinical Condition (PGA) of either complete clinical response (CCR) or partial response (PR). A complete clinical response (CCR) requires a grading of 0 indicating the absence of disease (histological confirmation is not required). Grades 1, 2, and 3 constitute partial response, indicating improvement of at least 50 percent, but less than 100 percent improvement. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
Measured: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Percentage of Participants With Renal Impairment
Renal Impairment was measured by glomerular filtration rate which was calculated using the Modification of Diet in Renal Disease formula. Percentage of participants with renal impairment was reported. Severe renal impairment was defined as a GFR of <30ml/min/1.73m2.
Measured: Day 1 up to 28 days after end of treatment
Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker
Blood samples for biomarker assessment were collected immediately prior to study administration. On-treatment samples was compared to baseline samples with the change from baseline.
Measured: 4 weeks, 12 weeks, 24 weeks, 36 weeks 48 weeks, 60 weeks, 72 weeks
Everolimus Trough Concentrations (Cmin)
Cmin values collected prior to dose administration on the same study day and at 20-28 hours after previous dose, at steady state, and patient did not vomit within 4 hours of previous dose. Samples collected during the first 4 days of dosing were excluded from all analyses.
Measured: Prior to dosing at weeks 2, 4, 12, 24, 48
Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose
C2h values collected 1-3 hours after dose administration on the same study day, at steady state, and patient did not vomit between taking previous dose and blood collection. Samples collected during the first 4 days of dosing will be excluded from all analyses.
Measured: 2 hours post-dose administration at Weeks 2, 4, 12, 24, 48
Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Time to angiomyolipoma response was defined as the time from the date of randomization until the date of the first documented angiomyolipoma response. Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; no kidney increases in volume > 20% from nadir; no angiomyolipoma-related bleeding of ≥ grade 2.
For the everolimus (core/extension periods) treatment group, the time to angiomyolipoma response is from the start of everolimus. The baseline in the response definition means the latest value on or before starting everolimus.
Measured: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Duration of angiomyolipoma response was defined as the time from the date of the first documented angiomyolipoma response until the date of the first documented angiomyolipoma progression . Angiomyolipoma response was defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2.
Measured: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years
Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR)
Duration of skin lesion response is defined as the time from the date of the first skin lesion response until the date of the first skin lesion progression, according to the PGA (physician's global assessment of clinical condition). A progression is when the disease is worse than at baseline evaluation by >=25% or more.
Measured: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startApr 2009
- Primary completionJun 2011
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Tuberous Sclerosis Complex (TSC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00790400
- Sponsor's protocol ID
- CRAD001M2302
- Other IDs
- 2008-002113-48, 2008
- Acronym
- EXIST-2
- Status last verified
- Jan 2017
- First submitted
- 10 Nov 2008
- Last updated
- 17 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Whittemore VH, Chen D, Sahmoud T, Shah G, Lincy J, Lebwohl D, Budde K. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013 Mar 9;381(9869):817-24. doi: 10.1016/S0140-6736(12)61767-X.
PubMed 23312829Bissler JJ, Nonomura N, Budde K, Zonnenberg BA, Fischereder M, Voi M, Louveau AL, Herbst F, Bebin EM, Curatolo P, Zonta A, Belousova E. Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. PLoS One. 2018 Sep 7;13(9):e0201005. doi: 10.1371/journal.pone.0201005. eCollection 2018.
PubMed 30192751Bissler JJ, Budde K, Sauter M, Franz DN, Zonnenberg BA, Frost MD, Belousova E, Berkowitz N, Ridolfi A, Christopher Kingswood J. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2019 Jun 1;34(6):1000-1008. doi: 10.1093/ndt/gfy132.
PubMed 30053159Sparagana S, Franz DN, Krueger DA, Bissler JJ, Berkowitz N, Burock K, Kingswood JC. Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. PLoS One. 2017 Oct 12;12(10):e0186235. doi: 10.1371/journal.pone.0186235. eCollection 2017.
PubMed 29023494Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Berkowitz N, Miao S, Segal S, Peyrard S, Budde K. Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial. Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.1093/ndt/gfv249. Epub 2015 Jul 8.
PubMed 26156073
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study of RAD0001 in the Treatment of Angiomyolipoma in Patients With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM)
- ClinicalTrials.gov ID
- NCT00790400
- Acronym / sponsor ID
- EXIST-2 / CRAD001M2302
- Keywords
- Angiomyolipoma, AML, Tuberous Sclerosis Complex, TSC, mTOR, RAD001, Mammalian Target of Rapamycin, Everolimus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2009
- Primary completion
- Jun 2011 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 13 Nov 2008 (estimated)
- Results
- Posted 28 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and efficacy of RAD001 in treating patients with Angiomyolipoma associated with Tuberous Sclerosis Complex or Sporadic Lymphangioleiomyomatosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Everolimus | Experimental | Drug: Everolimus (RAD001)Study drug was given by continuous oral daily dosing of two 5 mg tablets. |
| Placebo | Placebo comparator | Drug: Everolimus PlaceboPlacebo was given by continuous oral daily dosing of two 5 mg tablets. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or Female 18 years or older
- Clinically definite diagnosis of Tuberous Sclerosis Complex according to the modified Gomez criteria or sporadic LAM (biopsy-proven or compatible chest CT scan)
- Clinically definite diagnosis of renal angiomyolipoma
- At least one Angiomyolipoma of ≥ 3 cm in its longest diameter using CT or MRI
- Females of child bearing potential must use birth control and have documentation of negative pregnancy test
Key exclusion criteria (22 listed)
- Recent heart attack, cardiac related chest pain or stroke
- Severely impaired lung function
- Bleeding related to angiomyolipoma or embolization during 6 months prior to randomization
- Clinically significant chylous ascites
- Clinically significant hematological or hepatic abnormality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus (RAD001)Also: RAD001Everolimus is used in 5 mg strength tablets, blister-packed under aluminum foil in units of ten tablets and dosed on a daily basis. 10mg daily dosing throughout the trial. | Drug | Everolimus |
| Everolimus PlaceboMatching placebo was provided as a matching tablet and was also blister-packed under aluminum foil in units of ten. | Drug | Placebo |
Primary outcome
Angiomyolipoma Response Rate as Per Central Radiology Review
Time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Angiomyolipoma response defined as the combination of the following criteria: reduction in angiomyolipoma volume of ≥ 50% relative to baseline, where angiomyolipoma volume was sum of volumes of all target lesions identified at baseline, and with a confirmatory scan performed approximately 12 weeks later (no sooner than 8 weeks later); no new angiomyolipoma lesions ≥ 1.0 cm in longest diameter were identified; there were no kidney increases in volume > 20% from nadir. The patient did not have any angiomyolipoma-related bleeding of ≥ grade 2. For the everolimus (core/extension periods) treatment group, the baseline means the latest value on or before starting everolimus.
9 secondary outcomes
Time to Angiomyolipoma Progression as Per Central Radiology Review
Time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years
Skin Lesion Response Rate as Per Investigator (Only Patients With at Least One Skin Lesion at Baseline)
Time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Percentage of Participants With Renal Impairment
Time frame: Day 1 up to 28 days after end of treatment
Change From Baseline in Plasma Angiogenic Molecules - Vascular Endothelial Growth Factor (VEGF) Marker
Time frame: 4 weeks, 12 weeks, 24 weeks, 36 weeks 48 weeks, 60 weeks, 72 weeks
Everolimus Trough Concentrations (Cmin)
Time frame: Prior to dosing at weeks 2, 4, 12, 24, 48
Everolimus Blood Concentrations (C2h) at 2 Hours Post-dose
Time frame: 2 hours post-dose administration at Weeks 2, 4, 12, 24, 48
Time to Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years
Duration of Angiomyolipoma Response - Only Everolimus Patients With Angiomyolipoma Response
Time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years
Duration of Skin Lesion Response - Only Everolimus Patients With Best Overall Skin Lesion Response of Complete Clinical Response (CCR) or Partial Response (PR)
Time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to about 5.7 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23312829Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Whittemore VH, Chen D, Sahmoud T, Shah G, Lincy J, Lebwohl D, Budde K. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013 Mar 9;381(9869):817-24. doi: 10.1016/S0140-6736(12)61767-X.
- Derived from this study: PubMed 30192751Bissler JJ, Nonomura N, Budde K, Zonnenberg BA, Fischereder M, Voi M, Louveau AL, Herbst F, Bebin EM, Curatolo P, Zonta A, Belousova E. Angiomyolipoma rebound tumor growth after discontinuation of everolimus in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis. PLoS One. 2018 Sep 7;13(9):e0201005. doi: 10.1371/journal.pone.0201005. eCollection 2018.
- Derived from this study: PubMed 30053159Bissler JJ, Budde K, Sauter M, Franz DN, Zonnenberg BA, Frost MD, Belousova E, Berkowitz N, Ridolfi A, Christopher Kingswood J. Effect of everolimus on renal function in patients with tuberous sclerosis complex: evidence from EXIST-1 and EXIST-2. Nephrol Dial Transplant. 2019 Jun 1;34(6):1000-1008. doi: 10.1093/ndt/gfy132.
- Derived from this study: PubMed 29023494Sparagana S, Franz DN, Krueger DA, Bissler JJ, Berkowitz N, Burock K, Kingswood JC. Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. PLoS One. 2017 Oct 12;12(10):e0186235. doi: 10.1371/journal.pone.0186235. eCollection 2017.
- Derived from this study: PubMed 26156073Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, Frost M, Belousova E, Sauter M, Nonomura N, Brakemeier S, de Vries PJ, Berkowitz N, Miao S, Segal S, Peyrard S, Budde K. Everolimus for renal angiomyolipoma in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis: extension of a randomized controlled trial. Nephrol Dial Transplant. 2016 Jan;31(1):111-9. doi: 10.1093/ndt/gfv249. Epub 2015 Jul 8.
- Visit EXIST-2 NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
25 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Everolimus (RAD001) in people with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM), run by Novartis Pharmaceuticals at 25 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, United Kingdom, Italy, Japan, Germany and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Angiomyolipoma Response Rate as Per Central Radiology Review (time frame: From date of randomization until the earliest date of first documented AML progression, date of further anti-AML medication (including open-label Everolimus)/surgery or up to 5.7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00790400, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2017.