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.
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Facial Angiofibroma Severity Index (FASI)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 0 Years 至 2 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Topical everolimus 0.1%
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.).
干预措施: Everolimus (Drug)
Topical everolimus 0.5%
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.).
干预措施: Everolimus (Drug)
Topical everolimus 1%
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.).
干预措施: Everolimus (Drug)
Topical placebo
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.).
干预措施: Placebo (Drug)
结局指标
主要结局
Facial Angiofibroma Severity Index (FASI)
时间窗: 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.
次要结局
- blood levels of topically applied everolimus(6 months)
- Dermatologist's global assessment of efficacy(6 months)
- Dermatological quality of life(6 months)
- FA size(6 months)
- Patient or parents self-assessment(6 months)
- Local tolerance of the topically applied formulation using patient self-assessment(6 months)
- dryness score(6 months)
- scaling scores(6 months)