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Topical Everolimus in Patients With Tuberous Sclerosis Complex (EVEROST)

Primary Purpose

Facial Angiofibromas

Status
Withdrawn
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Everolimus
Placebo
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Facial Angiofibromas focused on measuring Tuberous sclerosis complex (TSC), topical everolimus, seamless design, dose-escalation study, m-TOR inhibitor

Eligibility Criteria

0 Years - 2 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • 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.

Sites / Locations

  • Hopital Femme Mère Enfant

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Topical everolimus 0.1%

Topical everolimus 0.5%

Topical everolimus 1%

Topical placebo

Arm Description

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.).

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.).

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.).

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.).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

FA size
FA size (in millimetres) of the 3 largest targeted FA papules previously identified by the investigator
Dermatologist's global assessment of efficacy
using 7-point Likert scale
Patient or parents self-assessment
using 7-point Likert scale
Local tolerance of the topically applied formulation using patient self-assessment
blood levels of topically applied everolimus
dryness score
assessed by physicians
scaling scores
assessed by physicians
Dermatological quality of life
using DLQI (Dermatology Life Quality Index) for adults, CDLQI (Children's Dermatology Life Quality Index) for children

Full Information

First Posted
August 4, 2016
Last Updated
April 28, 2021
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02860494
Brief Title
Topical Everolimus in Patients With Tuberous Sclerosis Complex
Acronym
EVEROST
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.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Pharmaceutical and financial difficulties
Study Start Date
December 2020 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Facial Angiofibromas
Keywords
Tuberous sclerosis complex (TSC), topical everolimus, seamless design, dose-escalation study, m-TOR inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Topical everolimus 0.1%
Arm Type
Experimental
Arm Description
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.).
Arm Title
Topical everolimus 0.5%
Arm Type
Experimental
Arm Description
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.).
Arm Title
Topical everolimus 1%
Arm Type
Experimental
Arm Description
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.).
Arm Title
Topical placebo
Arm Type
Placebo Comparator
Arm Description
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.).
Intervention Type
Drug
Intervention Name(s)
Everolimus
Intervention Description
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.).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.).
Primary Outcome Measure Information:
Title
Facial Angiofibroma Severity Index (FASI)
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
FA size
Description
FA size (in millimetres) of the 3 largest targeted FA papules previously identified by the investigator
Time Frame
6 months
Title
Dermatologist's global assessment of efficacy
Description
using 7-point Likert scale
Time Frame
6 months
Title
Patient or parents self-assessment
Description
using 7-point Likert scale
Time Frame
6 months
Title
Local tolerance of the topically applied formulation using patient self-assessment
Time Frame
6 months
Title
blood levels of topically applied everolimus
Time Frame
6 months
Title
dryness score
Description
assessed by physicians
Time Frame
6 months
Title
scaling scores
Description
assessed by physicians
Time Frame
6 months
Title
Dermatological quality of life
Description
using DLQI (Dermatology Life Quality Index) for adults, CDLQI (Children's Dermatology Life Quality Index) for children
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alice PHAN, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Femme Mère Enfant
City
Bron
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Topical Everolimus in Patients With Tuberous Sclerosis Complex

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