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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
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.).
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.).
Hopital Femme Mère Enfant
Bron, France
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.
Time frame: 6 months
FA size
FA size (in millimetres) of the 3 largest targeted FA papules previously identified by the investigator
Time frame: 6 months
Dermatologist's global assessment of efficacy
using 7-point Likert scale
Time frame: 6 months
Patient or parents self-assessment
using 7-point Likert scale
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
assessed by physicians
Time frame: 6 months
scaling scores
assessed by physicians
Time frame: 6 months
Dermatological quality of life
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using DLQI (Dermatology Life Quality Index) for adults, CDLQI (Children's Dermatology Life Quality Index) for children
Time frame: 6 months