Topical Everolimus in Patients With Tuberous Sclerosis Complex

NCT ID: NCT02860494

Last Updated: 2021-05-03

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2/PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-31
• Study Completion Date: 2024-12-31

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.

Conditions

Facial Angiofibromas

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.).

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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 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.).

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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 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.).

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

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

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.).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.).

Interventions

Everolimus

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

Placebo

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.).

Intervention Type: DRUG

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.

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alice PHAN, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Hopital Femme Mère Enfant

Bron, , France

Countries

France

Other Identifiers

2018-002531-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

69HCL16_0062

Identifier Type: -

Identifier Source: org_study_id