Facial AngiofibromasPhase 2/3EVEROSTNCT02860494
Topical Everolimus in Patients With Tuberous Sclerosis Complex
A Phase 2/3 study testing Everolimus in people with Facial Angiofibromas, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder characterized by the development of hamartomas in several organs (e.g. brain, heart, kidney, liver, lung), and skin in more than 90% of cases. Facial angiofibromas (FA), present in about 80% of patients, are a stigmatizing hallmark of the disease. Read more about this study
- Who is it for?
- Ages 0 to 2 years
- Conditions the study is for
- Facial Angiofibromas
- What is being tested?
- Everolimus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2020to Dec 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
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 0 to 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients over the age of 2 years
- With definite or possible diagnosis of TSC
- With at least 3 FA, diagnosed by a dermatologist
- Patients (or parents or legal guardians) who have provided written informed consent prior to participation in the study
- Willing and able to comply with study requirements
- With negative blood pregnancy test at the screening visit and using effective contraceptive methods for women of childbearing potential, up to 12 weeks after treatment discontinuation
- Covered by national health insurance
Who cannot join
- Systemic treatment by sirolimus, everolimus, or any other immunosuppressive drug, during the previous 6 months
- Use of topical tacrolimus or sirolimus on the face, during the previous 6 months
- Destructive treatment (laser therapy, surgery, cryotherapy) of facial angiofibromas during the previous 6 months
- Concomitant use of topical treatments that could affect facial erythema (e.g. Brimonidine)
- Known internal organ involvement requiring systemic mTOR inhibitor in the next 6 months
- Immunosuppression (immunosuppressive disease or immunosuppressive treatment)
Show all 15Show fewer
- Known chronic infectious disease Known hypersensitivity to mTOR inhibitor
- Neutropenia < 1000/mm3
- Thrombopenia < 75,000/mm3
- Chronic renal insufficiency (estimated Glomerular Filtration Rate < 60 mls/min)
- Chronic liver disease (SGOT or SGPT > 3 times upper normal limit)
- Uncontrolled dyslipidaemia
- Uncontrolled diabetes
- Brest feeding or pregnant women, or women on childbearing age without any effective method of contraception during treatment and up to 12 weeks after treatment discontinuation
- Subjects who, in the Investigator's opinion, are unable or unwilling to comply with the protocol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Topical Everolimus Versus Placebo for the Treatment of Facial Angiofibromas in Patients With Tuberous Sclerosis Complex. A Phase II/III, Multicentre, Randomized, Double-blind, Placebo-controlled Study of 3 Doses of Topical Everolimus.
Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder characterized by the development of hamartomas in several organs (e.g. brain, heart, kidney, liver, lung), and skin in more than 90% of cases. Facial angiofibromas (FA), present in about 80% of patients, are a stigmatizing hallmark of the disease. Everolimus could be a candidate for use as a topical formulation to treat FA. This adaptive seamless Phase II/III study primary objective is to determine the dose of topical everolimus for treatment of FA and evaluate the efficacy and safety of topical everolimus versus placebo in patients with angiofibromas.
- Conditions
- Facial Angiofibromas
- Being tested
- Everolimus, Placebo
- Keywords
- Tuberous sclerosis complex (TSC), topical everolimus, seamless design, dose-escalation study, m-TOR inhibitor
- Medical subject headings
- Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).
PlaceboDrug
Placebo topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months, by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.).
| Study group | Role | What they receive |
|---|---|---|
| Topical everolimus 0.1% | Experimental | Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). Receives: Drug: Everolimus |
| Topical everolimus 0.5% | Experimental | Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). Receives: Drug: Everolimus |
| Topical everolimus 1% | Experimental | Everolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). Receives: Drug: Everolimus |
| Topical placebo | Placebo comparator | Topical placebo will be identical to the everolimus topical formulation. Topical placebo will be applied to the affected areas, once daily, in the evening, for 6 months by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Facial Angiofibroma Severity Index (FASI)
The FASI is a composite score summing the scores for erythema (0-3), size (0-3) and extension of FA (2:<50% of the cheek surface; 3:>50% of the cheek surface). The FASI will be centrally-measured on patient's face photographs by an independent and blinded adjudication committee of 2 dermatologists, with third-dermatologist review for disagreements.
Measured: 6 months
Secondary outcomes (8)
FA size
FA size (in millimetres) of the 3 largest targeted FA papules previously identified by the investigator
Measured: 6 months
Dermatologist's global assessment of efficacy
using 7-point Likert scale
Measured: 6 months
Patient or parents self-assessment
using 7-point Likert scale
Measured: 6 months
Local tolerance of the topically applied formulation using patient self-assessment
Measured: 6 months
blood levels of topically applied everolimus
Measured: 6 months
dryness score
assessed by physicians
Measured: 6 months
scaling scores
assessed by physicians
Measured: 6 months
Dermatological quality of life
using DLQI (Dermatology Life Quality Index) for adults, CDLQI (Children's Dermatology Life Quality Index) for children
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study startDec 2020 (estimated)
- Primary completionDec 2023 (estimated)
- Study completionDec 2024 (estimated)
Why it stopped: Pharmaceutical and financial difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Facial AngiofibromasStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alice PHAN, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02860494
- Sponsor's protocol ID
- 69HCL16_0062
- Other IDs
- 2018-002531-18, 2018
- Acronym
- EVEROST
- Status last verified
- Apr 2021
- First submitted
- 4 Aug 2016
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical Everolimus Versus Placebo for the Treatment of Facial Angiofibromas in Patients With Tuberous Sclerosis Complex. A Phase II/III, Multicentre, Randomized, Double-blind, Placebo-controlled Study of 3 Doses of Topical Everolimus.
- ClinicalTrials.gov ID
- NCT02860494
- Acronym / sponsor ID
- EVEROST / 69HCL16_0062
- Conditions
- Facial Angiofibromas
- Keywords
- Tuberous sclerosis complex (TSC), topical everolimus, seamless design, dose-escalation study, m-TOR inhibitor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Pharmaceutical and financial difficulties
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Dec 2020 (estimated)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 9 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tuberous sclerosis complex (TSC) is a rare genetic multisystem disorder characterized by the development of hamartomas in several organs (e.g. brain, heart, kidney, liver, lung), and skin in more than 90% of cases. Facial angiofibromas (FA), present in about 80% of patients, are a stigmatizing hallmark of the disease. Everolimus could be a candidate for use as a topical formulation to treat FA. This adaptive seamless Phase II/III study primary objective is to determine the dose of topical everolimus for treatment of FA and evaluate the efficacy and safety of topical everolimus versus placebo in patients with angiofibromas.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Topical everolimus 0.1% | Experimental | Drug: EverolimusEverolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). |
| Topical everolimus 0.5% | Experimental | Drug: EverolimusEverolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). |
| Topical everolimus 1% | Experimental | Drug: EverolimusEverolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). |
| Topical placebo | Placebo comparator | Drug: PlaceboTopical placebo will be identical to the everolimus topical formulation. Topical placebo will be applied to the affected areas, once daily, in the evening, for 6 months by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). |
Who may qualify
- Ages
- 0 to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Patients over the age of 2 years
- With definite or possible diagnosis of TSC
- With at least 3 FA, diagnosed by a dermatologist
- Patients (or parents or legal guardians) who have provided written informed consent prior to participation in the study
- Willing and able to comply with study requirements
Key exclusion criteria (15 listed)
- Systemic treatment by sirolimus, everolimus, or any other immunosuppressive drug, during the previous 6 months
- Use of topical tacrolimus or sirolimus on the face, during the previous 6 months
- Destructive treatment (laser therapy, surgery, cryotherapy) of facial angiofibromas during the previous 6 months
- Concomitant use of topical treatments that could affect facial erythema (e.g. Brimonidine)
- Known internal organ involvement requiring systemic mTOR inhibitor in the next 6 months
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 |
|---|---|---|
| EverolimusEverolimus topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months. Dose regimens will be identical, regardless of the dose-strength of the topical formulation. The topical formulation will be applied onto areas of the face affected by FA by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). | Drug | Topical everolimus 0.1%, Topical everolimus 0.5%, Topical everolimus 1% |
| PlaceboPlacebo topical formulation will be applied to the affected areas, once daily, in the evening, for 6 months, by the patient or the patient's parents/legal guardians, while observing standardised precautions (avoiding the eyes, washing the hands after application, etc.). | Drug | Topical placebo |
Primary outcome
Facial Angiofibroma Severity Index (FASI)
Time frame: 6 months
The FASI is a composite score summing the scores for erythema (0-3), size (0-3) and extension of FA (2:<50% of the cheek surface; 3:>50% of the cheek surface). The FASI will be centrally-measured on patient's face photographs by an independent and blinded adjudication committee of 2 dermatologists, with third-dermatologist review for disagreements.
8 secondary outcomes
FA size
Time frame: 6 months
Dermatologist's global assessment of efficacy
Time frame: 6 months
Patient or parents self-assessment
Time frame: 6 months
Local tolerance of the topically applied formulation using patient self-assessment
Time frame: 6 months
blood levels of topically applied everolimus
Time frame: 6 months
dryness score
Time frame: 6 months
scaling scores
Time frame: 6 months
Dermatological quality of life
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Individual participant dataSharing planned: No
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.
Alice PHAN, MD principal investigator
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Everolimus in people with Facial Angiofibromas, run by Hospices Civils de Lyon at 1 site in France.
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 7 inclusion and 15 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: withdrawn, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Facial Angiofibroma Severity Index (FASI) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 May 2021.