angiofibromas MedDRA version: 20.0 Level: PT Classification code 10002429 Term: Angiofibroma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Everolimus
Pharmaceutical Form: Cream
INN or Proposed INN: EVEROLIMUS
CAS Number: 159351-69-6
Other descriptive name: EVER
Sponsors
Hospices Civils de Lyon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Male and female subjects > 2 years old. ? Subjects meeting the criteria for a definite or possible diagnosis of TSC ? Subjects with at least 3 FA, diagnosed by a dermatologist ? Women of child-bearing potential with a negative blood pregnancy test at the inclusion. ? Subjects or their parents or legal guardians must provide written informed consent prior to participation in the study ? Subjects covered by French national health insurance Are the trial subjects under 18? yes Number of subjects for this age range: 146 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: ? Systemic treatment by sirolimus, everolimus, or any other immunosuppressive drug, within 6 months pre inclusion. ? Use of topical tacrolimus or sirolimus on the face, within 6 months pre inclusion. ? Destructive treatment (laser therapy, surgery, cryotherapy) of facial angiofibroma, within 6 months pre inclusion. ? Current concomitant use of topical treatments that could affect facial erythema (e.g. bromonidine) ? 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 3 times upper normal limit) ? Uncontrolled dyslipidaemia ? Uncontrolled diabetes ? Breast feeding or pregnant women, or women of childbearing potential 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the phase II study is to identify the most appropriate dose of topical everolimus in terms of efficacy and safety and in the phase III, to demonstrate its superiority versus placebo for treatment of FA in patients with TSC after 6 months of treatment.; Secondary Objective: 1. To evaluate the efficacy of topical everolimus versus placebo by: Clinical assessment of FA (composite score); Blinded assessment of the redness using Reactiv’IP system; Assessment of the FA size reduction with topical everolimus versus placebo; Assessment of FA global improvement from patient’s and dermatologist’s perspectives; Improvement of quality of life of patients. 2. To correlate the results of the primary endpoint with the results of the clinical assessment of FA. 3. To evaluate safety of topical everolimus: Local tolerance of topical everolimus; Systemic safety of topical everolimus. ;Primary end point(s): The primary endpoint is the mean reduction of the validated and published score for assessment of angiofibromas, the Facial Angiofibroma Severity Index (FASI) after 6 months of treatment.;Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy assessments a. Clinical assessment of FA: Mean reduction of a composite clinical score (0-12) for FA. b. Blinded assessment of the redness and extension using Reactiv’IP system. c. FA size (in millimetres) of the 3 largest targeted FA papules. d. Global improvement of FA on a 7-point Likert scale i. Dermatologist’s global assessment of efficacy ii. Patient or parents self-assessment e. Dermatological quality of life of patients, self-assessment using 2 validated dermatological surveys, both available in French: i. DLQI (Dermatology Life Quality Index) for adults ii. CDLQI (Children's Dermatology Life Quality Index) for children 2. Correlation of the results of FASI blindly assessed and the clinical assessment of FA 3. Safety of topical everolimus a. Local tolerance of the topical formulation applied: i. Patient self-assessment: composite scores of 5 items (stinging, burning, itching, dryness, and scaling), each item consists of 3 states: 0=absent, 1=mild, 2=moderate and 3=severe. ii. The physicians will assess dryness and scaling scores. b. Safety of the topical formulation applied: i. Quantification of blood levels of topical everolimus. ii. Laboratory assessments (creatinine, serum electrolytes including Na, K, Cl, CO2, Ca, Total protein and Urea, liver enzymes, total cholesterol, triglycerides, glucose, complete blood count). iii. Adverse events and serious adverse events ;Timepoint(s) of evaluation of this end point: Day-21, 1, month 1,month 2, month 3, month 4, month 5 et month 6 | — |
Countries
France
Contacts
Public ContactDRCI
Hospices Civils de Lyon
Outcome results
None listed